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CAVEAT:

This is a VERY long and detailed article which in full runs to over 10,000 words – with, at the end, LINKS to almost 2,000 other articles related to The Prostate!

Prostate Cancer: Stages and Grades

Approved by the Cancer.Net Editorial Board, 01/2017

ON THIS PAGE: You will learn about how doctors describe a cancer’s growth or spread, as well as what the cancer cells look like under a microscope. This is called the stage and grade. To see other pages, use the menu.

Staging is a way of describing where the cancer is located, if or where it has spread, and whether it is affecting other parts of the body.

Doctors use diagnostic tests to find out the cancer’s stage, so staging may not be complete until all of the tests are finished. Staging for prostate cancer also involves looking at test results to find out if the cancer has spread from the prostate to other parts of the body. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient’s prognosis, which is the chance of recovery. There are different stage descriptions for different types of cancer.

There are 2 types of staging for prostate cancer:

  • The clinical stage is based on the results of tests done before surgery, which includes DRE, biopsy, x-rays, CT and/or MRI scans, and bone scans. X-rays, bone scans, CT scans, and MRI scans may not always be needed. They are recommended based on the PSA level; the size of the cancer, which includes its grade and volume; and the clinical stage of the cancer.
  • The pathologic stage is based on information found during surgery, plus the laboratory results, referred to as pathology, of the prostate tissue removed during surgery. The surgery often includes the removal of the entire prostate and some lymph nodes.

TNM staging system

One tool that doctors use to describe the stage is the TNM system. Doctors use the results from diagnostic tests and scans to answer these questions:

  • Tumor (T): How large is the primary tumor? Where is it located?
  • Node (N): Has the tumor spread to the lymph nodes? If so, where and how many?
  • Metastasis (M): Has the cancer metastasized to other parts of the body? If so, where and how much?

The results are combined to determine the stage of cancer for each person. There are 5 stages: stage 0 (zero) and stages I through IV (1 through 4). The stage provides a common way of describing the cancer, so doctors can work together to plan the best treatments.

Here are more details about each part of the TNM system for prostate cancer.

Tumor (T)

Using the TNM system, the “T” plus a letter or number (0 to 4) is used to describe the size and location of the tumor. Some stages are also divided into smaller groups that help describe the tumor in even more detail. Specific tumor stage information is listed below.

TX: The primary tumor cannot be evaluated.

T0 (T plus zero): There is no evidence of a tumor in the prostate.

T1: The tumor cannot be felt during a DRE and is not seen during imaging tests. It may be found when surgery is done for another reason, usually for BPH or an abnormal growth of noncancerous prostate cells.

  • T1a: The tumor is in 5% or less of the prostate tissue removed during surgery.
  • T1b: The tumor is in more than 5% of the prostate tissue removed during surgery.
  • T1c: The tumor is found during a needle biopsy, usually because the patient has an elevated PSA level.

T2: The tumor is found only in the prostate, not other parts of the body. It is large enough to be felt during a DRE.

  • T2a: The tumor involves one-half of 1 lobe (part or side) of the prostate.
  • T2b: The tumor involves more than one-half of 1 lobe of the prostate but not both lobes.
  • T2c: The tumor has grown into both lobes of the prostate.

T3: The tumor has grown through the prostate capsule on 1 side and into the tissue just outside the prostate.

  • T3a: The tumor has grown through the prostate capsule either on 1 side or on both sides of the prostate, or it has spread to the neck of the bladder. This is also known as an extraprostatic extension (EPE).
  • T3b: The tumor has grown into the seminal vesicle(s), the tube(s) that carry semen.

T4: The tumor is fixed, or it is growing into nearby structures other than the seminal vesicles, such as the external sphincter, the part of the muscle layer that helps to control urination; the rectum; levator muscles; or the pelvic wall.

Node (N)

The “N” in the TNM staging system stands for lymph nodes. These tiny, bean-shaped organs help fight infection. Lymph nodes near the prostate in the pelvic region are called regional lymph nodes. Lymph nodes in other parts of the body are called distant lymph nodes.

NX: The regional lymph nodes cannot be evaluated.

N0 (N plus zero): The cancer has not spread to the regional lymph nodes.

N1: The cancer has spread to the regional (pelvic) lymph node(s).

Metastasis (M)

The “M” in the TNM system indicates whether the prostate cancer has spread to other parts of the body, such as the lungs or the bones. This is called distant metastasis.

MX: Distant metastasis cannot be evaluated.

M0 (M plus zero): The disease has not metastasized.

M1: There is distant metastasis.

  • M1a: The cancer has spread to nonregional, or distant, lymph node(s).
  • M1b: The cancer has spread to the bones.
  • M1c: The cancer has spread to another part of the body, with or without spread to the bone.

Cancer stage grouping

Doctors assign the stage of the cancer by combining the T, N, and M classification. See the table below the stage descriptions for all of the TNM combinations for each stage.

Stage I: Cancer is found in the prostate only, usually during another medical procedure. It cannot be felt during the DRE or seen on imaging tests. A stage I cancer is usually made up of cells that look more like healthy cells and is usually slow growing. 

Stage I Prostate Cancer

Stage IIA and IIB: This stage describes a tumor that is too small to be felt or seen on imaging tests. Or, it describes a slightly larger tumor that can be felt during a DRE. The cancer has not spread outside of the prostate gland, but the cells are usually more abnormal and may tend to grow more quickly. A stage II cancer has not spread to lymph nodes or distant organs. 

Stage IIA Prostate Cancer

Stage IIB Prostate Cancer

Stage III: The cancer has spread beyond the outer layer of the prostate into nearby tissues. It may also have spread to the seminal vesicles. 

Stage I Prostate Cancer

Stage IV: This stage describes any tumor that has spread to other parts of the body, such as the bladder, rectum, bone, liver, lungs, or lymph nodes. 

Stage IV Prostate Cancer

Recurrent: Recurrent prostate cancer is cancer that has come back after treatment. It may come back in the prostate area again or in other parts of the body. If the cancer does return, there will be another round of tests to learn about the extent of the recurrence. These tests and scans are often similar to those done at the time of the original diagnosis.

Stage Grouping Chart

Stage

T

N

M

I

T1a, T1b, or T1c

N0

M0

T2a

N0

M0

Any T1 or T2a

N0

M0

 

 

 

 

IIA

T1a, T1b, or T1c

N0

M0

T1a, T1b, or T1c

N0

M0

 

T2a

N0

M0

 

T2b

N0

M0

 

T2b

N0

M0

 

 

 

 

IIB

T2c

N0

M0

 

Any T1 or T2

N0

M0

 

Any T1 or T2

N0

M0

 

 

 

 

III

T3a or T3b

N0

M0

 

 

 

 

 

 

 

IV

T4

N0

M0

Any T

N1

M0

 

Any T

Any N

M1

Used with permission of the AJCC, Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition, published by Springer-Verlag New York, www.cancerstaging.org

Gleason score for grading prostate cancer

Prostate cancer is also given a grade called a Gleason score. This score is based on how much the cancer looks like healthy tissue when viewed under a microscope. Less aggressive tumors generally look more like healthy tissue. Tumors that are more aggressive are likely to grow and spread to other parts of the body. They look less like healthy tissue.

The Gleason scoring system is the most common prostate cancer grading system used. The pathologist looks at how the cancer cells are arranged in the prostate and assigns a score on a scale of 1 to 5. Cancer cells that look similar to healthy cells receive a low score. Cancer cells that look less like healthy cells or look more aggressive receive a higher score. To assign the numbers, the doctor determines the main pattern of cell growth, which is the area where the cancer is most obvious; looks for any other less common pattern of growth; and gives each 1 a score. The scores are added together to come up with an overall score between 2 and 10.

The interpretation of the Gleason score by doctors has changed recently. Originally, doctors used a wide range of scores. Today, doctors no longer use Gleason scores of 5 or lower for cancer found with a biopsy. The lowest score used is 6, which is a low-grade cancer. A Gleason score of 7 is a medium-grade cancer, and a score of 8, 9, or 10 is a high-grade cancer. A lower-grade cancer grows more slowly and is less likely to spread than a high-grade cancer.

Doctors look at the Gleason score in addition to stage to help plan treatment. For example, active surveillance, described in the Treatment Options section, may be an option for a patient with a small tumor, low PSA level, and a Gleason score of 6. Patients with high Gleason score may need treatment that is more intensive, even if it does not appear that the cancer has spread.

Gleason X: The Gleason score cannot be determined.

Gleason 6 or lower: The cells are well differentiated, meaning they look similar to healthy cells.

Gleason 7: The cells are moderately differentiated, meaning they look somewhat similar to healthy cells.

Gleason 8, 9, or 10: The cells are poorly differentiated or undifferentiated, meaning they look very different from healthy cells.

Recently, pathologists have begun to adopt a new Gleason grouping system that arranges the scores into simplified groups that are translated as follows:

  • Gleason Group I = Former Gleason 6
  • Gleason Group II = Former Gleason 3 + 4 = 7
  • Gleason Group III = Former Gleason 4 + 3 = 7
  • Gleason Group IV = Former Gleason 8
  • Gleason Group V = Former Gleason 9 or 10

Prostate Cancer Risk Groups

In addition to stage, doctors use other prognostic factors to help plan the best treatment and predict how successful treatment will be. Two such risk assessment methods come from the National Comprehensive Cancer Network (NCCN) and the University of California, San Francisco (UCSF).

NCCN

The NCCN developed 4 risk-group categories based on PSA level, prostate size, needle biopsy findings, and the stage of cancer. The lower your risk, the lower the chance that the prostate cancer will grow and spread.

  • Very low risk. The tumor cannot be felt during a DRE and is not seen during imaging tests but was found during a needle biopsy (T1c). PSA is less than 10 ng/mL. The Gleason score is 6 or less. Cancer was found in fewer than 3 samples taken during a core biopsy. The cancer was found in half or less of any core.
  • Low risk. The tumor is classified as T1a, T1b, T1c, or T2a (see above). PSA is less than 10 ng/mL. The Gleason score is 6 or less.
  • Intermediate risk. The tumor has 2 or more of these characteristics:
    • Classified as T2b or T2c (see above)
    • PSA is between 10 and 20 ng/mL
    • Gleason score of 7
  • High risk. The tumor has 2 or more of these characteristics:
    • Classified as T3a (see above)
    • PSA level is higher than 20 ng/mL
    • Gleason score is between 8 and 10
  • Very high risk. The tumor is classified as T3b or T4 (see above). The histologic grade is 5 for the main pattern of cell growth, or more than 4 biopsy cores have Gleason scores between 8 and 10.

Source: Risk group information is adapted from the NCCN.

UCSF Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score

The UCSF-CAPRA score predicts a man’s chances of having the cancer spread and of dying. This score can be used to help make decisions about the treatment plan. Points are assigned according to a person’s age at diagnosis, PSA at diagnosis, Gleason score of the biopsy, T classification from the TNM system, and the percentage of biopsy cores involved with cancer. These categories are then used to assign a score between 0 and 10.

  • CAPRA score 0 to 2 indicates low risk.
  • CAPRA score 3 to 5 indicates intermediate risk.
  • CAPRA score 6 to 10 indicates high risk.   

Information about the cancer’s stage and other prognostic factors will help the doctor recommend a specific treatment plan. The next section in this guide is Treatment Options. Or, use the menu to choose another section to continue reading this guide.

To view the original of this article CLICK HERE
BELOW:
is another, even more detailed article, on Gleason Grading or Staging

Gleason grading system

Links

- Susan J. Maygarden and Raj Pruthi. Gleason Grading and Volume Estimation in Prostate Needle Biopsy Specimens Am J Clin Pathol Pathology Patterns Reviews 2005 123:S58-S66; doi : PDF)

- Grading of prostatic adenocarcinoma: current state and prognostic implications
Jennifer Gordetsky and Jonathan Epstein. Diagnostic Pathology 2016; 11:25. doi : 10 1186/s13000-016-0478-2 (Free)

Historical background

In the 1960s and 1970s, Donald F. Gleason and collaborators characterized various architectural patterns of prostatic cancer and grouped them into five grades or patterns, thus establishing the Gleason grading system.

More than four decades since its introduction, the Gleason system still remains the key prognostic factor in patients with prostatic cancer.

The Gleason system was derived largely from observations in larger specimens, such as prostatectomy and transurethral prostatic resection specimens.

Donald F. Gleason in 1966 created a unique grading system for prostatic carcinoma based solely on the architectural pattern of the tumor.

Another innovative aspect of this system was, rather than assigning the worst grade as the grade of the carcinoma, the grade was defined as the sum of the two most common grade patterns and reported as the Gleason score. The original description of this system was based on a study of 270 patients from the Minneapolis Veterans Administration Hospital.

Initially, Gleason intended to classify carcinomas into four Gleason patterns (GPs), but a small group of distinctive tumors (clear cell) was observed and they were placed in a separate 5th category (pattern 4).

Certain aspects of the original Gleason system would be interpreted differently in today’s practice. The cribriform pattern described, as a component of Gleason’s original pattern 2 and 3 would today typically be considered higher grade.

Individual cells listed under Gleason’s original pattern 3 would also be currently assigned a higher grade.

Pattern 4 has become significantly expanded beyond Gleason’s original description of tumors with clear cytoplasm that resembled renal cell carcinoma.

By 1974, Gleason and the Veterans Administration Cooperative Urological Research Group expanded their study to 1,032 men.

Gleason pattern 4 was described in a figure legend, as “raggedly infiltrating, fused-glandular tumor, frequently with pale cells, may resemble hypernephroma of kidney.”

The Gleason system was further refined by Mellinger in 1977 when the papillary and cribriform tumor under Gleason pattern 3 was described as having a “smooth and usually rounded edge”.

In describing the breakdown of Gleason patterns amongst 2,911 cases, Gleason pattern 1 was seen in 3.5%; pattern 2 in 24.4%; pattern 3 in 87.7%; pattern 4 in 12.1%; and pattern 5 in 22.6%.

These percentages added up to approximately 150% since 50% of the tumors showed at least two different patterns.

In 1977, Gleason provided additional comments concerning the application of the Gleason system. “Grading is performed under low magnification (40-100x).” He also stated “an occasional small area of fused glands did not change a pattern 3 tumor to pattern 4. A small focus of disorganized cells did not change a pattern 3 or 4 tumor to pattern 5.”

The only comment relating to tertiary patterns was “occasionally, small areas of a third pattern were observed.”

Synopsis Gleason Grade or Gleason Pattern Identification

The Gleason Grade is also known as the Gleason Pattern and ranges from 1 to 5:

- Gleason Grade 1 – Here, cancerous tissue is well differentiated and looks like normal prostate tissue. Glands are well packed and formed.
- Gleason Grade 2 – Here, well-formed large glands have more tissue between them.
- Gleason Grade 3 – Glands begin to look darker and show signs of randomness. They seem to be breaking away from monotony of their existence and invading surrounding tissue.
- Gleason Grade 4 – Majority of glands appear to be interspersed with surrounding tissue. A few recognizable glands are still present though.
- Gleason Grade 5 – There are no recognizable glands. Cells with distinct nuclei appear in sheets within surrounding tissue.

Description

Numerous grading systems have been designed for histopathological grading of prostate cancer. The main controversies have been whether grading should be based on glandular differentiation alone or a combination of glandular differentiation and nuclear atypia, and also whether prostate cancer should be graded according to its least differentiated or dominant pattern.

The Gleason grading system named after Donald F. Gleason is now the predominant grading system, and in 1993, it was recommended by a WHO consensus conference.

As described by Gleason, the initial grading of prostate carcinoma should be performed at low magnification using a 4x or 10x lens.

After one assesses the case at scanning magnification, one may proceed to use the 20x lens to verify the grade. For example, at low magnification one may have the impression of fused glands or necrosis but may require higher magnification at 20x to confirm its presence.

However, one should not initially use the 20x or 40x objectives to look for rare fused glands or a few individual cells seen only at higher power which would lead to an overdiagnosis of Gleason pattern 4 or 5, respectively.

The Gleason grading system is based on glandular architecture; nuclear atypia is not evaluated. Nuclear atypia as adopted in some grading systems, correlates with prognosis of prostate cancer but there is no convincing evidence that it adds independent prognostic information to that obtained by grading glandular differentiation alone.

The Gleason grading system defines five histological patterns or grades with decreasing differentiation.

- Normal prostate epithelial cells are arranged around a lumen.
- In Gleason patterns 1 to 3, there is retained epithelial polarity with luminal differentiation in virtually all glands.
- In pattern 4, there is partial loss of normal polarity.
- In pattern 5, there is an almost total loss of polarity with only
occasional luminal differentiation.

Prostate cancer has a pronounced morphological heterogeneity and usually more than one histological pattern is present.

The primary and secondary pattern, i.e. the most prevalent and the second most prevalent pattern are added to obtain a Gleason score or sum.

It is recommended that the primary and secondary pattern as well as the score be reported, e.g. Gleason score 3+4=7.

If the tumour only has one pattern, Gleason score is obtained by doubling that pattern, e.g. Gleason score 3+3=6.

Gleason scores 2 and 3 are only exceptionally assigned, because Gleason pattern 1 is unusual.

Gleason score 4 is also relatively uncommon because pattern 2 is usually mixed with some pattern 3 resulting in a Gleason score 5.

Gleason score 2-4 tumour may be seen in TURP material sampling the transitional zone.

With the introduction of the needle core biopsy technique, the Gleason system evolved to accommodate needle biopsy practice, in which the grading was done on limited biopsy core tissue.

In needle biopsy material, it has been proposed that a Gleason score of 2-4 should not be assigned. Gleason scores 6 and 7 are the most common scores and include the majority of tumours in most studies.

Gleason pattern 1

Gleason pattern 1 is composed of a very well circumscribed nodule of separate, closely packed glands, which do not infiltrate into adjacent benign prostatic tissue. The glands are of intermediate size and approximately equal in size and shape. This pattern is usually seen in transition zone cancers. Gleason pattern 1 is exceedingly rare. When present, it is usually only a minor component of the tumour and not included in the Gleason score.

Gleason pattern 2

Gleason pattern 2 is composed of round or oval glands with smooth ends. The glands are more loosely arranged and not quite as uniform in size and shape as those of Gleason pattern 1. There may
be minimal invasion by neoplastic glands into the surrounding non-neoplastic prostatic tissue. The glands are of intermediate size and larger than in Gleason pattern 3. The variation in glandular size and separation between glands is less than that seen in pattern 3. Although not evaluated in Gleason grading, the cytoplasm of Gleason pattern 1 and 2 cancers is abundant and pale-staining. Gleason pattern 2 is usually seen in transition zone cancers but may occasionally be found in the peripheral zone.

Gleason pattern 3

Gleason pattern 3 is the most common pattern. The glands are more infiltrative and the distance between them is more variable than in patterns 1 and 2. Malignant glands often infiltrate between adjacent non-neoplastic glands. The glands of pattern 3 vary in size and shape and are often angular. Small glands are typical for pattern 3, but there may also be large, irregular glands. Each gland has an open lumen and is circumscribed by stroma. Cribriform pattern 3 is rare and difficult to distinguish from cribriform high-grade PIN.

Gleason pattern 4

In Gleason pattern 4, the glands appear fused, cribriform or they may be poorly defined. Fused glands are composed of a group of glands that are no longer completely separated by stroma. The edge of a group of fused glands is scalloped and there are occasional thin strands of connective tissue within this group. Cribriform pattern 4 glands are large or they may be irregular with jagged edges. As opposed to fused glands, there are no strands of stroma within a cribriform gland. Most cribriform invasive cancers should be assigned a pattern 4 rather than pattern 3. Poorly defined glands do not have a lumen that is completely encircled by epithelium. The hypernephromatoid pattern described by Gleason is a rare variant of fused glands with clear or very pale staining cytoplasm.

Gleason pattern 5

In Gleason pattern 5, there is an almost complete loss of glandular lumina. Only occasional lumina may be seen. The epithelium forms solid sheets, solid strands or single cells invading the stroma. Care must be applied when assigning a Gleason pattern 4 or 5 to limited cancer on needle biopsy to exclude an artefact of tangential sectioning of lower grade cancer. Comedonecrosis may be present.

Grade progression

The frequency and rate of grade progression is unknown. Tumour grade is on average higher in larger tumours. However, this may be due to more rapid growth of high grade cancers. It has been demonstated that some tumours are high grade when they are small.

Many studies addressing the issue of grade progression have a selection bias, because the patients have undergone a repeat transurethral resection or repeat biopsy due to symptoms of tumour progression.

The observed grade progression may be explained by a growth advantage of a tumour clone of higher grade that was present from the beginning but undersampled. In patients followed expectantly there is no evidence of grade progression within 1-2 years.

Grading minimal cancer on biopsy

It is recommended that a Gleason score be reported even when a minimal focus of cancer is present. The correlation between biopsy and prostatectomy Gleason score is equivalent or only marginally worse with minimal cancer on biopsy. It is recommended that even in small cancers with one Gleason pattern that the Gleason score be reported. If only the pattern is reported, the clinician may misconstrue this as the Gleason score.

Tertiary Gleason patterns

The original Gleason grading system does not account for patterns occupying less than 5% of the tumour or for tertiary patterns.

In radical prostatectomy specimens, the presence of a tertiary high
grade component adversely affects prognosis. However, the prognosis is not necessarily equated to the addition of the primary Gleason pattern and the tertiary highest Gleason pattern.

For example, the presence of a tertiary Gleason pattern 5 in a Gleason score 4+3=7 tumour worsens the prognosis compared to the same tumour without a tertiary high grade component.

However, it is not associated with as adverse prognosis as a Gleason score 4+5=9. When this tertiary pattern is pattern 4 or 5, it should be reported in addition to the Gleason score, even when it is less than 5% of the tumour.

Although comparable data do not currently exist for needle biopsy material, in the setting of three grades on biopsy where the highest grade is the least common, the highest grade is incorporated as the secondary pattern.

An alternative option is in the situation with a tertiary high grade pattern (i.e. 3+4+5 or 4+3+5) is to diagnose the case as Gleason score 8 with patterns 3, 4 and 5 also present.

The assumption is that a small focus of high grade cancer on biopsy will correlate with a significant amount of high grade cancer in the prostate such that the case overall should be considered high grade, and that sampling artefact accounts for its limited nature on biopsy.

Reporting Gleason scores in cases with multiple positive biopsies

In cases where different positive cores have divergent Gleason scores, it is controversial whether to assign an averaged (composite) Gleason score or whether the highest Gleason score should be considered as the patient’s grade.

In practice, most clinicians take the highest Gleason score when planning treatment options.

Grading of variants of prostate cancer

Several morphological variants of prostate adenocarcinoma have been described (e.g. mucinous and ductal cancer).

They are almost always combined with conventional prostate cancer and their effect on prognosis is difficult to estimate.

In cases with a minor component of a prostate cancer variant, Gleason grading should be based on the conventional prostate cancer present in the specimen.

In the rare case where the variant form represents the major component, it is controversial whether to assign a Gleason grade.

Grading of specimens with artefacts and treatment effect

Crush artefacts

Crush artefacts are common at the margins of prostatectomy specimens and in core biopsies. Crush artefacts cause disruption of the glandular units and consequently may lead to overgrading
of prostate cancer. These artefacts are recognized by the presence of noncohesive epithelial cells with fragmented cytoplasm and dark, pyknotic nuclei adjacent to preserved cells. Crushed areas should not be Gleason graded.

Hormonal and radiation treatment

Prostate cancer showing either hormonal or radiation effects can appear artefactually to be of higher Gleason score. Consequently, Gleason grading of these cancers should not be performed. If there is cancer that does not show treatment effect, a Gleason score can be assigned to these components.

Correlation of needle biopsy and prostatectomy grade

Prostate cancer displays a remarkable degree of intratumoural grade heterogeneity. Over 50% of total prostatectomy specimens contain cancer of at least three different Gleason grades, and cancer of a single grade is present in only 16% of the specimens.

Of individual tumour foci, 58% have a single grade, but most of these foci are very small.

Several studies have compared biopsy and prostatectomy Gleason score. Exact correlation has been observed in 28.2-67.9% of the cases. The biopsies undergraded in 24.5-60.0% and overgraded in 5.2-32.2%.

Causes for biopsy grading discrepencies are undersampling of higher or lower grades, tumours borderline between two grade patterns, and misinterpretation of patterns.

The concordance between biopsy and prostatectomy Gleason score is within one Gleason score in more than 90% of cases.

Reproducibility

Pathologists tend to undergrade. The vast majority of tumours graded as Gleason score 2 to 4 on core biopsy are graded as Gleason score 5 to 6 or higher when reviewed by experts in urological pathology.

In a recent study of interobserver reproducibility amongst general pathologists, the overall agreement for Gleason score groups 2-4, 5-6, 7, and 8-10 was just into the moderate range.

Undergrading is decreased with teaching efforts and a substantial interobserver reproducibility can be obtained.

Prognosis

Multiple studies have confirmed that Gleason score is a very powerful prognostic factor on all prostatic samples. This includes the prediction of the natural history of prostate cancer and the assessment of the risk of recurrence after total prostatectomy or radiotherapy.

Several schedules for grouping of Gleason scores in prognostic categories have been proposed.

Gleason scores 2 to 4 behave similarly and may be grouped.

Likewise, Gleason scores 8 to 10 are usually grouped together, although they could be stratified with regard to disease progression in a large prostatectomy study.

There is evidence that Gleason score 7 is a distinct entity with prognosis intermediate between that of Gleason scores 5-6 and 8 to 10, respectively.

Although the presence and amount of high grade cancer (patterns 4 to 5) correlates with tumour prognosis, reporting the percentage pattern 4/5 is not routine clinical practice.

Gleason score 7 cancers with a primary pattern 4 have worse prognosis than those with a primary pattern 3.

ISUP 2005 modifications

A group of urological pathologists convened at the 2005 United States and Canadian Academy meeting in San Antonio in an attempt to achieve consensus in controversial areas relating to the Gleason grading system.

The goal of the meeting was to achieve consensus amongst leading urological pathologists in specific areas of Gleason grading, including areas where there was either a lack of data or scant information as to the optimal method of grading.

In the latter instances, the consensus was based on personal and institutional experience with a large number of cases. Over 70 urological pathologists from around the world were invited to attend, with most attending.

For the purposes of this meeting, we defined “consensus” when two-thirds of the participants were in agreement, although for almost all of the issues discussed a much higher degree of agreement was reached.

See also : ISUP 2005 modifified Gleason score

At the turn of the century, attempts and recommendations were made in order to clarify how the Gleason system should be applied in practice, since it was evident that differences in Gleason system interpretation and application existed.

However, several issues remained unresolved, as this system was ultimately dependent on a subjective interpretation of various morphological patterns of cancer.

For example, it was unclear what extent of variations in size and shape of neoplastic glands should be scored as Gleason pattern (GP) 3 and what represented the scope of gland fusion patterns, interpreted as GP4.

Additional problematic issues included the grading of ill-defined glands with poorly formed lumina, defining the morphological spectrum of cribriform glands, and the grading of a tertiary grade, when it was higher than the primary and secondary grades.

In order to resolve these and other issues pertaining to Gleason grading in practice, the International Society of Urological Pathology (ISUP) convened a consensus conference on Gleason grading at the 2005 United States and Canadian Academy of Pathology Annual Meeting in San Antonio, TX, USA.

Uropathologists from 20 countries attempted to clarify and standardize the contemporary use of the Gleason system by providing consensus recommendations, based on accumulated evidence and practice standards, as to how the Gleason system should be applied and reported in contemporary practice.

Thus, a 2005 ISUP modified Gleason system was proposed, outlining the morphological patterns 1–5, which were accompanied by a modified diagram, similar to the original Gleason system.

It was reiterated that GP1 and GP2 are quite rare on biopsy and prostatectomy.

The most significant modifications pertained to patterns 3 and 4.

GP3 was restricted to discrete glandular units (as in the original system) and to smoothly circumscribed but only small cribriform tumour nodules, which, in essence, reduced the spectrum of cribriform glands interpreted as pattern 3.

Pattern 4 included fused glands and large cribriform glands or cribriform glands with border irregularities, as well as hypernephromatoid glands.

Additionally, a category of ill-defined glands or glands containing poorly formed glandular lumina was introduced (not present previously) and was included under GP4.

GP5 was reserved for cancers containing essentially no glandular differentiation, composed of solid sheets, cords, and single cells, as in the original system.

Comedocarcinoma with central necrosis was also retained in pattern 5, regardless of whether it was surrounded by papillary, cribriform or solid sheets.

The consensus also provided clarifications on the grading of variants and variations of acinar adenocarcinoma of prostate, which were illustrated by examples.

These included the issues of interpretation and grading of: vacuoles, foamy gland cancer, ductal adenocarcinoma, colloid (mucinous) carcinoma, small cell carcinoma, adenocarcinoma with focal mucinous extravasation, mucinous fibroplasia (collagenous micronodules), glomeruloid structures, and pseudohyperplastic carcinoma.

The consensus also recommended that secondary patterns of higher grade when present to a limited extent (≤5% of the tumour area) should always be reported on needle biopsy, while there was no consensus on reporting on prostatectomy.

Secondary patterns of lower grade when present to a limited extent (≤5% of the tumour area) in needle biopsies, prostatectomies and transurethral resections of prostate should be ignored.

Regarding the issue of tertiary GP, it was recommended that the Gleason score (GS) on needle biopsy should be derived by adding the primary and the highest pattern, whereas tertiary pattern on prostatectomy, when it is higher than the primary and the secondary patterns, should be reported separately.

Another recommendation was that separate dominant tumour nodules of different Gleason patterns should be scored separately on prostatectomy.

Finally, it was recommended that individual Gleason scores should be reported on needle biopsy specimens with different cores showing different grades, as long as the cores are submitted in separate containers. In addition, it was left as an option to provide an overall GS at the end of the case.

The impact of these recommendations on prostatic cancer grading in contemporary practice remains unknown, because they were introduced relatively recently and because it is uncertain how much they have penetrated and potentially altered routine prostatic pathology practice.

Hence, the objective of this study was to determine whether and how the proposed ISUP consensus recommendations have influenced the application of the modified Gleason system in grading biopsy and prostatectomy specimens in a contemporary setting of a large uropathology practice.

Reporting secondary patterns of lower grade when present to a limited extent

It was the consensus of the ISUP group that in the setting of high-grade cancer one should ignore lower grade patterns if they occupy less than 5% of the area of the tumor.

For example, a needle biopsy core that is 100% involved by cancer, with 98% Gleason pattern 4 and 2% Gleason pattern 3 would be diagnosed as Gleason score 4+4=8.

These cases with extensive pattern 4 cancer, where a significant amount of tumor is available for examination, should be considered as high grade (Gleason score>8).

At the other extreme, one can occasionally see small foci of Gleason pattern 4 on needle biopsy with a few glands of pattern 3. In the setting of very limited cancer on needle biopsy, the few glands of pattern 3 would typically occupy over 5% of the area of the tumor focus, and one would grade these tumors as Gleason score 4+3=7. Given the significant potential in this scenario of a sampling error resulting from only limited cancer on biopsy, the presence of a relatively small amount of pattern 3 would most likely correspond to a Gleason score 7 tumor in the corresponding prostate. The same 5% cut off rule for excluding lower grade cancer also applies for TURPs and radical prostatectomy specimens, which in most cases would relate to extensive cancer with more than 95% Gleason pattern 4 tumor.

Reporting secondary patterns of higher grade when present to a limited extent

It was the consensus of the group that high-grade tumor of any quantity on needle biopsy, as long as it was identified at low to medium magnification (see General applications of the Gleason grading system) should be included within the Gleason score. Any amount of high grade tumor sampled on needle biopsy most likely indicates a more significant amount of high grade tumor within the prostate due to the correlation of grade and volume and the problems inherent with needle biopsy sampling. Consequently, a needle biopsy which is entirely involved by cancer with 98% Gleason pattern 3 and 2% Gleason pattern 4 would be diagnosed as Gleason score 3+4=7.

In radical prostatectomy specimens with the analogous situation of a tumor nodule having 98% Gleason pattern 3 and 2% pattern 4, there was no consensus within the group. Approximately half of the group would diagnose these foci in an analogous fashion to that done on needle biopsy and interpret the case as Gleason score 3+4=7 regardless of the percentage of pattern 4. The other half would note these tumors as Gleason score 3+3=6 with a minor component of Gleason pattern 4. The rationale for the latter method is based on radical prostatectomy data; cancers with more than 95% Gleason pattern 3 and less than 5% pattern 4 have pathological stages that are worse than a pure Gleason score 3+3=6 tumor yet not as adverse as a Gleason score 3+4=7 where pattern 4 occupies more than 5% of the tumor.

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Historical background

Donald F. Gleason in 1966 created a unique grading system for prostatic carcinoma based solely on the architectural pattern of the tumor [1, 2, 3]. Another innovative aspect of this system was, rather than assigning the worst grade as the grade of the carcinoma, the grade was defined as the sum of the two most common grade patterns and reported as the Gleason score. The original description of this system was based on a study of 270 patients from the Minneapolis Veterans Administration Hospital.

Initially, Gleason intended to classify carcinomas into four patterns, but a small group of distinctive tumors (clear cell) was observed and they were placed in a separate 5th category (pattern 4) [2]. Certain aspects of the original Gleason system would be interpreted differently in today’s practice. The cribriform pattern described, as a component of Gleason’s original pattern 2 and 3 would today typically be considered higher grade. Individual cells listed under Gleason’s original pattern 3 would also be currently assigned a higher grade. Pattern 4 has become significantly expanded beyond Gleason’s original description of tumors with clear cytoplasm that resembled renal cell carcinoma.

By 1974, Gleason and the Veterans Administration Cooperative Urological Research Group expanded their study to 1,032 men [4]. Gleason pattern 4 was described in a figure legend, as “raggedly infiltrating, fused-glandular tumor, frequently with pale cells, may resemble hypernephroma of kidney.” The Gleason system was further refined by Mellinger in 1977 when the papillary and cribriform tumor under Gleason pattern 3 was described as having a “smooth and usually rounded edge” [5]. In describing the breakdown of Gleason patterns amongst 2,911 cases, Gleason pattern 1 was seen in 3.5%; pattern 2 in 24.4%; pattern 3 in 87.7%; pattern 4 in 12.1%; and pattern 5 in 22.6% [5]. These percentages added up to approximately 150% since 50% of the tumors showed at least two different patterns.

In 1977, Gleason provided additional comments concerning the application of the Gleason system [6]. “Grading is performed under low magnification (40-100x).” He also stated “an occasional small area of fused glands did not change a pattern 3 tumor to pattern 4. A small focus of disorganized cells did not change a pattern 3 or 4 tumor to pattern 5.” The only comment relating to tertiary patterns was “occasionally, small areas of a third pattern were observed.”
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Why the need for a consensus on Gleason grading?

It is a testament to the enduring power of the original Gleason grading system that it is the accepted grading system throughout the world, despite its inception almost 40 years ago. How many other things in medicine have stood the test of time so well? Nonetheless, medicine in general and prostate carcinoma in specific has changed dramatically since the late 1960s, when the Gleason grading system was derived. In the 1960s, there was no screening for prostate cancer other than by digital rectal exam, as serum PSA had not yet been discovered. In Gleason’s 1974 study, the vast majority (86%) of men had advanced disease with either local extension out of the prostate on clinical exam or distant metastases. Only 6% of patients had nonpalpable tumor diagnosed by transurethral resection and 8% of patients were diagnosed with a localized nodule on rectal exam [4]. The method of obtaining prostate tissue was also very different from today’s practice. Typically, only a couple of thick gauge needle biopsies were directed into an area of palpable abnormality. The use of 18-gauge thin biopsy needles and the concept of sextant needle biopsies to more extensively sample the prostate were not developed until the 1980s [7]. Consequently, the grading of prostate cancer in thin cores and in multiple cores from different sites of the prostate were not issues in Gleason’s era.

In the 1960s, radical prostatectomy was relatively uncommon, prostates were not as often removed intact, and glands were not processed in their entirety or as extensively and systematically to the degree currently seen. Further issues relating to radical prostatectomy specimens such as the grading of multiple nodules within the same prostate or dealing with tertiary patterns were not addressed within the original Gleason system.

The Gleason system also predated the use of immunohistochemistry. It is likely that with immunostaining for basal cells many of Gleason’s original 1+1=2 adenocarcinomas of the prostate would today be regarded as adenosis (atypical adenomatous hyperplasia). Similarly, many of the cases in 1967 diagnosed as cribriform Gleason pattern 3 carcinoma would probably be currently referred to as cribriform high grade prostatic intraepithelial neoplasia (PIN) or intraductal carcinoma of the prostate, if labeled with basal cell markers [8, 9].

Another issue not dealt with in the original Gleason grading system is how to grade newly described variants of adenocarcinoma of the prostate. Some of the more common variants where grading controversy exists include: mucinous carcinoma, ductal adenocarcinoma, foamy gland carcinoma, and pseudohyperplastic adenocarcinoma of the prostate. In addition, there are certain patterns of adenocarcinoma of the prostate such as those with glomeruloid features and mucinous fibroplasia (collagenous micronodules) where the use of Gleason grading was not defined.

The application of the Gleason system for all of the reasons noted above varies considerably in contemporary surgical pathology practice and has led to several recent attempts to achieve consensus on Gleason grading.
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2005 ISUP consensus conference

A group of urological pathologists convened at the 2005 United States and Canadian Academy meeting in San Antonio in an attempt to achieve consensus in controversial areas relating to the Gleason grading system [10]. The goal of the meeting was to achieve consensus amongst leading urological pathologists in specific areas of Gleason grading, including areas where there was either a lack of data or scant information as to the optimal method of grading. In the latter instances, the consensus was based on personal and institutional experience with a large number of cases. Over 70 urological pathologists from around the world were invited to attend, with most attending. For the purposes of this meeting, we defined “consensus” when two-thirds of the participants were in agreement, although for almost all of the issues discussed a much higher degree of agreement was reached.
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General applications of the Gleason grading system

As described by Gleason, the initial grading of prostate carcinoma should be performed at low magnification using a 4x or 10x lens. After one assesses the case at scanning magnification, one may proceed to use the 20x lens to verify the grade. For example, at low magnification one may have the impression of fused glands or necrosis but may require higher magnification at 20x to confirm its presence. However, one should not initially use the 20x or 40x objectives to look for rare fused glands or a few individual cells seen only at higher power which would lead to an overdiagnosis of Gleason pattern 4 or 5, respectively.

Gleason patterns
Gleason score 1+1=2

It was the consensus that a Gleason score of 1+1=2 is a grade that should not be diagnosed regardless of the type of specimen, with extremely rare exception. Most cases which were diagnosed as Gleason score 1+1=2 in the era of Gleason would today be referred to as adenosis (atypical adenomatous hyperplasia).
Gleason scores 3-4

These low-grade tumor scores were assigned by members of the consensus panel occasionally on transurethral resection specimens (TURPs) and in multifocal low-grade tumors within radical prostatectomy specimens. In contrast to Gleason’s diagram and text, the consensus was that cribriform patterns are not allowed within Gleason pattern 2. It is now accepted that Gleason score 2-4 should not be assigned to cancer on needle biopsy for several reasons:

poor reproducibility even amongst experts;

poor correlation with prostatectomy grade with almost all cases showing higher grade at resection;

a diagnosis of Gleason score 3-4 may misguide clinicians and patients into believing that the patient has an indolent tumor [11, 12].

The major limitation of rendering a diagnosis of Gleason score 4 on needle biopsy is that one cannot see the entire edge of the lesion to determine if it is completely circumscribed. Consequently, most of the lesions that appear to be very low grade on needle biopsies are diagnosed by urological pathologists as Gleason score 2+3=5 or 3+2=5.
Gleason pattern 3

A departure from the original Gleason classification system is that “individual cells” would not be allowed within Gleason pattern 3. Rather, Gleason pattern 3 cancer consists of variably sized individual glands. A further area of divergence from the original Gleason system is the controversial area of cribriform Gleason pattern 3. Within Gleason’s original illustrations of his cribriform pattern 3, he depicts large cribriform glands, which the consensus panel would uniformly diagnose as cribriform pattern 4. The consensus panel required extremely stringent criteria for the diagnosis of cribriform pattern 3, with remaining cribriform patterns typically falling into Gleason pattern 4. The criteria used to diagnose cribriform pattern 3 were rounded, well circumscribed glands of the same size of normal glands. When various images were shown to the consensus panel of potential candidates for cribriform Gleason pattern 3, almost none of them met the criteria based on subtle features, such as slight irregularities of the outer border of the cribriform glands. Subsequent to the 2005 meeting, this author reviewed 3590 consecutive prostate cancers sent to me over seven months; 30 needle biopsy cases were selected that possibly represented cribriform Gleason pattern 3 cancer [13], 36 digital images were taken and sent to ten experts in prostate pathology with a consensus defined when at least 7/10 experts agreed on the grade. Even in this highly selected set of images thought to be the best candidates for cribriform pattern 3 from a busy consult service, most experts interpreted the cribriform patterns as pattern 4. There was only one consensus pattern 3 case. Furthermore, most of the cribriform foci investigated (73%) were associated with more definitive pattern 4 elsewhere on the needle biopsy specimen. There was poor reproducibility amongst experts as to cribriform pattern 3 vs. pattern 4 due to:

disagreement as to what are the key diagnostic features in a given case (i.e. irregular distribution of lumina and variable slit-like lumina, favor pattern 4 vs. small glands and regular contour, favor pattern 3;

disagreement as to assessment of given criteria: regular vs. irregular distribution of lumina and regular vs. irregular contour.

Conceptually, one would expect the change in grade from pattern 3 to pattern 4 to be reflected in a distinct architectural paradigm shift where cribriform as opposed to individual glands are formed, rather than merely a subjective continuum of differences in size, shape and contour of cribriform glands.

The only reason why cribriform pattern 3 even exists is because of the original Gleason schematic diagram. Gleason never specifically published the prognostic difference between what he called cribriform Gleason pattern 3 compared to Gleason pattern 4. Many of Gleason’s cribriform Gleason pattern 3 cancers may not even have been infiltrating carcinomas due to the lack of availability of immunohistochemistry for basal cell markers. Today we might have diagnosed them either as cribriform high-grade PIN or intraductal carcinoma of the prostate (concepts not present in Gleason’s era). Based on all the above data, all cribriform cancer should be interpreted as Gleason pattern 4 and not pattern 3.
Gleason pattern 4

A controversial area where consensus was reached was that ill-defined glands with poorly formed glandular lumina also warrant the diagnosis of Gleason pattern 4. Only a cluster of such glands, where a tangential section of Gleason pattern 3 glands cannot account for the histology, would be acceptable as Gleason pattern 4. It was also noted that in most cases ill-defined glands with poorly formed glandular lumina are accompanied by fused glands. Very small, well-formed glands still are within the spectrum of Gleason pattern 3. This definition differs from Gleason’s original description of pattern 4 which only included the hypernephromatoid pattern [2]. Only in subsequent years were fused glandular masses added to the definition [5]. The original schematic diagram of Gleason pattern 4 consisted almost entirely of cribriform patterns without depicting fused glands or ill-defined glands with poorly formed glandular lumina. Gleason pattern 4 closely resembling renal cell carcinoma (hypernephromatoid pattern) makes up only a very small percentage of Gleason pattern 4 cases.
Gleason pattern 5

Gleason pattern 5 consists of individual cells, cords of cells, and sheets of tumor. Although typically one sees comedonecrosis with solid nests, occasionally one can see necrosis with cribriform masses that by themselves might be cribriform pattern 4. If there is true comedonecrosis, the consensus was that these patterns should be regarded as Gleason pattern 5. One must be stringent as to the definition of comedonecrosis, requiring intraluminal necrotic cells and/or karyorrhexis, especially in the setting of cribriform glands. We have noted in two studies using different patient populations the tendency for pathologists to undergrade Gleason pattern 5 in almost 50% of cases sent for a second opinion at the request of the patient of urologist where this author has diagnosed Gleason pattern 5. Pattern 5 was missed more frequently when it was not the primary pattern.

Grading variants and variations of acinar adenocarcinoma of the prostate
Vacuoles

Adenocarcinomas of the prostate may contain clear vacuoles and these should be distinguished from true signet-ring carcinomas which contain mucin. Whereas vacuoles in adenocarcinoma of the prostate are not uncommon, true mucin-positive signet-ring cell carcinomas of prostate are exceedingly rare with only a handful of bona fide cases reported in the literature. Vacuoles may distort the architecture and it is controversial as to what grade should be assigned. Gleason’s only mention of vacuoles described them as signet cells under pattern 5 tumor [6]. The panel concluded that although typically vacuoles are seen within Gleason pattern 4 cancer, it may be seen within Gleason pattern 5 and even Gleason pattern 3 tumors. The consensus was that tumors should be graded, as if the vacuoles were not present, by only evaluating the underlying architectural pattern.
Foamy gland carcinoma

In an analogous fashion to handling cancers with vacuoles, it was the consensus of the panel that in grading foamy gland carcinomas one should ignore the foamy cytoplasm and grade the tumor solely based on the underlying architecture. Whereas most cases of foamy gland carcinoma would be graded as Gleason score 3+3=6, higher grade foamy gland carcinomas exist and should be graded accordingly based on the pattern [14, 15].
Ductal adenocarcinoma

Ductal adenocarcinomas of the prostate most commonly are composed of either papillary fronds or cribriform structures [16]. Ductal adenocarcinomas are recognized as being aggressive tumors with most studies showing comparable behavior to acinar cancer with a Gleason score 4+4=8. The consensus of the panel was that ductal adenocarcinomas should be graded as Gleason score 4+4=8, while retaining the diagnostic term of ductal adenocarcinoma to denote their unique clinical and pathological findings. This can be achieved by diagnosing such a tumor as “prostatic ductal adenocarcinoma (Gleason score 4+4=8).” In cases with mixed ductal and acinar patterns, the ductal patterns should be assigned Gleason pattern 4. The only exceptions to grading ductal adenocarcinoma as Gleason pattern 4 are:

PIN-like ductal adenocarcinoma;

ductal adenocarcinoma with comedonecrosis.

PIN-like ductal adenocarcinoma consists of individual glands lined by tall pseudostratified columnar cells resembling high grade PIN [17]. Its prognosis appears comparable to Gleason pattern 3. Although it has not been specifically studied, ductal adenocarcinoma with comedonecrosis is graded as Gleason pattern 5.
Colloid (mucinous) carcinoma

The majority of cases with colloid carcinoma consist of irregular cribriform glands floating within a mucinous matrix [18, 19]. It was the uniform consensus that these cases would be scored Gleason score 4+4=8. However, uncommonly one may see individual round discrete glands floating within mucinous pools. There was no consensus in these cases whether such cases should be diagnosed as Gleason score 4+4=8 or Gleason score 3+3=6. Approximately half of the group said that by definition all colloid carcinomas should be assigned a Gleason score of 8, while the other half felt that one should ignore the extracellular mucin and grade the tumor based on the underlying architectural pattern. The excellent prognosis of mucinous carcinomas in a large study of mucinous carcinoma at radical prostatectomy supports grading mucinous prostate carcinomas based on the underlying architectural pattern rather than assuming that all of these tumors are aggressive [20].
Small cell carcinoma

It was the consensus that small cell carcinoma of the prostate has unique histological, immunohistochemical, and clinical features [21]. Comparable to its more common pulmonary counterpart, chemotherapy is the mainstay of therapy for prostatic small cell carcinomas. These clinicopathologic features differ from those associated with Gleason pattern 5 prostatic acinar carcinoma, such that small cell carcinoma should not be assigned a Gleason grade.
Adenocarcinoma with focal mucin extravasation

There was consensus amongst the group that adenocarcinomas of the prostate with focal mucinous extravasation should not be by default graded as Gleason score 4+4=8. Rather, one should ignore focal mucinous extravasation and grade the tumor based on the underlying architecture of the glands. The distinction between focal mucinous extravasation and colloid carcinoma is the presence of epithelial elements floating within the mucinous matrix within the latter whereas with mucinous extravasation there is only focal acellular mucin adjacent to cancer.
Mucinous fibroplasia (collagenous micronodules)

The delicate ingrowth of fibrous tissue seen with mucinous fibroplasia can result in glands appearing to be fused resembling cribriform structures although the underlying architecture is really that of individual discrete rounded glands invested by loose collagen. The tumor should be graded on the underlying glandular architecture, whereby the majority are graded as Gleason score 3+3=6 [22]. Only when there are distinct cribriform glands in areas of mucinous fibroplasias does this author diagnose Gleason pattern 4.
Glomeruloid structures

Glomeruloid glands in prostatic adenocarcinoma are characterized by dilated glands containing intraluminal cribriform structures with a single point of attachment, resembling a renal glomerulus [22]. On prostate biopsy, glomeruloid glands are exclusively associated with carcinoma and not associated with benign mimickers. The grading of such glomeruloid structures is controversial. Some urological pathologists do not assign a grade to glomeruloid patterns and rather just grade the surrounding tumor. According to some experts for the rare case where the entire tumor is composed of glomeruloid glands, a grade of 3+3=6 is assigned as long as the glomeruloid structures are small. Larger glomeruloid structures are uniformly accepted by urological pathologists as Gleason pattern 4. Other experts in the field feel that all glomeruloid structures should be assigned a Gleason pattern 4. A study of ours, subsequent to the consensus conference, indicated that glomerulations were overwhelmingly associated with concurrent Gleason pattern 4 or higher-grade carcinoma [23]. In several cases, transition could be seen among small glomerulations, large glomeruloid structures, and cribriform pattern 4 cancer. These data suggest that glomerulations represent an early stage of cribriform pattern 4 cancer and are best graded as Gleason pattern 4.
Pseudohyperplastic adenocarcinoma

Uncommonly, adenocarcinomas of the prostate share some architectural features with benign glands, including larger size, branching, and papillary infolding. These cancers should be graded as Gleason score 3+3=6 with pseudohyperplastic features [24, 25]. This convention is in large part based on the recognition that they are most often accompanied by more ordinary Gleason score 3+3=6 adenocarcinoma.

Reporting secondary patterns of lower grade when present to a limited extent

It was the consensus of the group that in the setting of high-grade cancer one should ignore lower grade patterns if they occupy less than 5% of the area of the tumor. For example, a needle biopsy core that is 100% involved by cancer, with 98% Gleason pattern 4 and 2% Gleason pattern 3 would be diagnosed as Gleason score 4+4=8. These cases with extensive pattern 4 cancer, where a significant amount of tumor is available for examination, should be considered as high grade (Gleason score>8). At the other extreme, one can occasionally see small foci of Gleason pattern 4 on needle biopsy with a few glands of pattern 3. In the setting of very limited cancer on needle biopsy, the few glands of pattern 3 would typically occupy over 5% of the area of the tumor focus, and one would grade these tumors as Gleason score 4+3=7. Given the significant potential in this scenario of a sampling error resulting from only limited cancer on biopsy, the presence of a relatively small amount of pattern 3 would most likely correspond to a Gleason score 7 tumor in the corresponding prostate. The same 5% cut off rule for excluding lower grade cancer also applies for TURPs and radical prostatectomy specimens, which in most cases would relate to extensive cancer with more than 95% Gleason pattern 4 tumor.

Reporting secondary patterns of higher grade when present to a limited extent

It was the consensus of the group that high-grade tumor of any quantity on needle biopsy, as long as it was identified at low to medium magnification (see General applications of the Gleason grading system) should be included within the Gleason score. Any amount of high grade tumor sampled on needle biopsy most likely indicates a more significant amount of high grade tumor within the prostate due to the correlation of grade and volume and the problems inherent with needle biopsy sampling. Consequently, a needle biopsy which is entirely involved by cancer with 98% Gleason pattern 3 and 2% Gleason pattern 4 would be diagnosed as Gleason score 3+4=7.

In radical prostatectomy specimens with the analogous situation of a tumor nodule having 98% Gleason pattern 3 and 2% pattern 4, there was no consensus within the group. Approximately half of the group would diagnose these foci in an analogous fashion to that done on needle biopsy and interpret the case as Gleason score 3+4=7 regardless of the percentage of pattern 4. The other half would note these tumors as Gleason score 3+3=6 with a minor component of Gleason pattern 4. The rationale for the latter method is based on radical prostatectomy data; cancers with more than 95% Gleason pattern 3 and less than 5% pattern 4 have pathological stages that are worse than a pure Gleason score 3+3=6 tumor yet not as adverse as a Gleason score 3+4=7 where pattern 4 occupies more than 5% of the tumor [26, 27].

Tertiary Gleason patterns

Needle biopsy

On needle biopsies with patterns 3, 4, and 5, both the primary pattern and the highest grade should be recorded, which is a departure from the original Gleason grading system [10]. For example, tumors with Gleason score 3+4 and a tertiary pattern 5 would be recorded as Gleason score 3+5=8. Men with biopsy Gleason score 7 with tertiary pattern 5 have a higher risk of PSA failure whether treated with radical prostatectomy or radiation therapy when compared to men with Gleason score 7 without tertiary grade 5 and have a comparable risk with men with Gleason score 8-10 [28, 29]. In cases where there are three patterns consisting of patterns 2, 3, and 4, pattern 2 is ignored and the biopsy is graded as Gleason score 3+4=7 or Gleason score 4+3=7, depending on whether pattern 3 or pattern 4 was more prevalent.

Radical prostatectomy

In radical prostatectomy specimens, tertiary Gleason patterns are associated with higher pathological stage and biochemical recurrence as compared to the same Gleason score cancers without tertiary patterns. [26, 27, 30, 31, 32, 33, 34, 35]. The presence of a tertiary higher grade component is associated with an increased risk of biochemical recurrence, typically raising the risk of recurrence to a level intermediate between those of cancers without a tertiary component in the same Gleason score category and cancers in the next higher Gleason score category. The one exception is Gleason score 4+3=7 with tertiary pattern 5, which has progression rates more comparable to Gleason score 8. Typically, the tertiary pattern is added to the Gleason score (i.e. 3+4=7 with tertiary pattern 5).

Radical prostatectomy specimens with separate tumor nodules

It was recommended that radical prostatectomy specimens should be processed in an organized fashion where one can make some assessment as to whether one is dealing with a dominant nodule or separate tumor nodules. This does not necessarily require serially sectioning and embedding a radical prostatectomy in its entirety. Rather, multiple sampling techniques have described how one can subtotally submit the prostate, yet still maintain orientation in order to distinguish between different tumor nodules [36, 37, 38]. This issue becomes critical in the situation where one has a higher-grade peripheral nodule and a smaller, typically transition zone, lower-grade nodule. One can have a nodule of Gleason score 4+4=8 within the peripheral zone and a Gleason score 2+2=4 nodule within the transition zone. Occasionally these Gleason score 2+2=4 transition zone tumors may even reach relatively sizable proportions although typically they are organ-confined. If one were to assign an overall score considering all of the tumor within the prostate as one lesion, the score of such a tumor would be Gleason score 4+2=6 or Gleason score 2+4=6. It was the consensus of the group that such a grade would be misleading as it is not logical to expect that the presence of a lower grade tumor that is discrete from a separate high grade tumor nodule could in some way mitigate the poor prognosis associated with the higher grade tumor nodule. It was also recognized that if a tumor was graded, for example, as Gleason score 4+2=6 or 2+4=6, the presence of pattern 4 within such a diagnosis would not be emphasized and the patient would typically merely be recorded as having a Gleason score 6 tumor, which would not accurately reflect the nature of his lesion. The recommendation of the consensus conference was that one should assign a separate Gleason score to each dominant tumor nodule(s). With only a couple of exceptions, pathologists within the consensus conference who were authors of large radical prostatectomy series had already adopted this method of grading and the prognostic impact of the Gleason score within these series already reflects this approach. Most often, the dominant nodule is the largest tumor, which is also the tumor associated with the highest stage and highest grade. In the unusual occurrence of a non-dominant nodule (i.e. smaller nodule) that is of higher stage, one should also assign a grade to that nodule. If one of the smaller nodules is the highest grade focus within the prostate, the grade of this smaller nodule should also be recorded. In general this will be the exception; in most cases, separate grades will be assigned to only one or at most two dominant nodules.

Needle biopsy with different cores showing different grades

In current practice within the United States, a minimum of ten to 12 cores are sampled for the initial biopsy to rule out prostate cancer. In cases where multiple cores are positive for cancer, different cores may have a different Gleason grade. What overall grade should be assigned to such a patient for purposes of treatment and prognosis? This issue assumes its greatest importance when one or more of the cores show pure high-grade cancer (i.e. Gleason score 4+4=8) and the other cores show pattern 3 (3+3=6, 3+4=7, 4+3=7) cancer. Should the overall grade be the core with the highest grade or does one assign the grade by mentally adding all the cancer together as if it was one long core. Assume a case with Gleason score 4+4=8 on one core with pattern 3 (3+3=6, 3+4=7, 4+3=7) on other cores. The “Global” score for the entire case, averaging all involved needle biopsies together as if they were one long positive core, would be 4+3=7 or 3+4=7 depending on whether pattern 4 or 3 predominated.

Several studies have demonstrated that in cases with different cores having different grades, the highest Gleason score on a given core correlates better with stage and Gleason score at radical prostatectomy than the average or most frequent grade amongst the cores [39, 40, 41]. Additional support for giving cores a separate grade rather than an overall score for the entire case is that all of the various tables (i.e. Partin tables) and nomograms that have been validated and proven to be prognostically useful have used the highest core grade in cases where there are multiple cores of different grades.

It is therefore incumbent on pathologists to report the grades of each core separately as long as the cores are submitted in separate containers or the cores are in the same container yet specified by the urologist as to their location (i.e. by different color inks). As a consequence, the core with the highest grade tumor can be selected by the clinician as the grade of the entire case to determine treatment [42, 43]. In addition to giving separate cores individual Gleason scores, it is an option for pathologists to also give an overall score at the end of the case.

There is no consensus how to grade different cores with different grades when the different cores are present within the same specimen container without a designation as to site [10]. For example, there may be two cores of tissue from the left base in one jar without further designation, or multiple cores divided into containers from the left and right side of the gland. If more than one core contains cancer in the setting of multiple cores per container, some urological pathologists still grade each core separately with the remaining experts in the field giving an overall grade for the involved cores per specimen container. A rationale for the latter approach is that it is implicit that clinicians submitting multiple cores together in one container do not value the specific information derived from the cores within a given container. On the other hand, assigning a Gleason score to each core even when there are multiple positive cores in a given jar provides the most accurate information for patient care.

In cases with multiple fragmented cores in a jar, only an overall Gleason score for that jar can be assigned. For example, diagnosing Gleason score 4+4=8 on a tiny tissue fragment where there are other fragments with Gleason score 3+3=6 could be in error; if the cores were intact and the tumor was all on one core, it would be assigned a Gleason score 3+4=7 or 4+3=7.

Prognostic Gleason grade grouping

A problem with the current system is that Gleason score 6 is typically recommended as the lowest grade assigned on biopsy material. However, the Gleason scale ranges from 2-10, such that patients are unduly concerned when told they have Gleason score 6 cancer on biopsy, logically but incorrectly assuming that their tumor is in mid-range of aggressiveness. Another problem is that Gleason score 7 tumor is often considered as one grade, without distinction of 3+4=7 and 4+3=7. Finally, most studies combine Gleason scores 8-10 as high grade cancer without differentiating Gleason score 9-10 from Gleason score 8.

Based on a series of 6,462 men treated by radical prostatectomy (RP) where both the needle biopsy and RP were graded using the current modified Gleason grading system, the 5-year biochemical free survival rates for men with 3+3, 3+4, 4+3, 8, and 9-10 at biopsy were 94.6%, 82.7%, 65.1%, 63.1%, and 34.5% respectively (p < 0.001 for trend); and 96.6%, 88.1%, 69.7%, 63.7%, and 34.5% based on RP pathology respectively (p < 0.001).

It has been proposed the following Gleason grade groups and reporting of grade that accurately reflects prognosis while incorporating descriptive terminology:

- Gleason score 2-6 (well-differentiated), prognostic grade group I/V;
- Gleason score 3+4=7 (moderately differentiated), prognostic grade group II/V;
- Gleason score 4+3=7 (moderately-poorly differentiated), prognostic grade group III/V;
- Gleason score 8 (poorly differentiated), prognostic grade group IV/V;
- Gleason score 9-10 (undifferentiated), Prognostic grade group V/V.

See also

- tumoral grade
- prostate cancer

  • prostate adenocarcinoma
    • prostate acinar adenocarcinoma

References

- Update on the Gleason grading system. Jonathan I. Epstein. Ann Pathol. 2011 Nov;31(5 Suppl):S20-6. PMID: 22054451. (Link)

- Diagnosis of limited adenocarcinoma of the prostate. Epstein JI. Histopathology. 2012 Jan;60(1):28-40. PMID: 22212076

- The impact of the 2005 International Society of Urological Pathology (ISUP) consensus on Gleason grading in contemporary practice. Zareba P, Zhang J, Yilmaz A, Trpkov K. Histopathology. 2009 Oct;55(4):384-91. PMID: 19817888

- Gleason DF. Classification of prostatic carcinoma. Cancer Chemother. Rep. 1966; 50; 125–128.

- Bailar JC 3rd, Mellinger GT, Gleason DF. Survival rates of patients with prostatic cancer, tumor stage, and differentiation: preliminary report. Cancer Chemother. Rep. 1966; 50; 129–136.

- Mellinger GT, Gleason DF, Bailar JC 3rd. The histology and prognosis of prostatic cancer. J. Urol. 1967; 97; 331–337.

- Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J. Urol. 1974; 111; 58–64.

- Gleason DF and the Veterans Administration Cooperative Urological Research Group. Histologic grading and clinical staging of prostate carcinoma. In TannenbaumM ed. Urologic pathology: the prostate. Philadelphia, PA: Lea & Febiger, 1977; 171–198.

- Mellinger GT. Prognosis of prostatic carcinoma. Recent Results Cancer Res. 1977; 60; 61–72.

- Association of Directors of Anatomical and Surgical Pathology. Recommendations for reporting of resected prostate carcinomas. Am. J. Clin. Pathol. 1996; 105; 667–670.

- Srigley JR, Amin MB, Bostwick DG et al. Updated protocol for the examination of specimens from patients with carcinoma of the prostate gland: a basis for checklist. Arch. Pathol. Lab. Med. 2000; 124; 1034–1039.

- Epstein JI. Gleason score 2–4 adenocarcinoma of the prostate on needle biopsy: a diagnosis that should not be made. Am. J. Surg. Pathol. 2000; 24; 477–478.

- Epstein JI, Yang XJ. Grading of prostatic adenocarcinoma. In EpsteinJI, YangXJ eds. Prostate biopsy interpretation, 3rd edn. Philadelphia: Lippincott Williams & Wilkins, 2002; 154–176.

- Amin MB, Grignon DJ, Humphrey PA, Srigley JR. Reporting of prostate carcinoma by the Gleason system. In AminMB, GrignonDJ, HumphreyPA, SrigleyJR eds. Gleason grading of prostate cancer: a contemporary approach. Philadelphia, PA: Lippincott Williams & Wilkins, 2004; 101–111.

- Egevad L, Allsbrook WC, Epstein JE. Current practice of Gleason grading among genitourinary pathologists. Hum. Pathol. 2005; 36; 5–9.

- Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL and the ISUP Grading Committee. The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am. J. Surg. Pathol. 2005; 29; 1228–1242.

- Nakanishi H, Wang X, Ochai A et al. A nomogram for predicting low-volume/low grade prostate cancer: a tool in selecting patients for active surveillance. Cancer 2007; 110; 2441–2447.

- Trpkov K, Warman L. Use of digital maps and sampling of radical prostatectomy specimens. Arch. Pathol. Lab. Med. 2006; 130; 1751–1752.

- Schellhammer P, Moriarty R, Bostwick D, Kuban D. Fifteen-year minimum follow-up of a prostate brachytherapy series: comparing the past with the present. Urology 2000; 50; 436–439.

- Gilliland FD, Gleason DF, Hunt WC, Stone N, Harlan LC, Key CR. Trends in Gleason score for prostate cancer diagnosed between 1983–1993. J. Urol. 2001; 165; 846–850.

- Smith EB, Frierson HF Jr, Mills SE, Boyd JC, Theodorescu D. Gleason score of prostate biopsy and radical prostatectomy specimens over past 10 years. Cancer 2002; 94; 2282–2287.

- Chism DB, Hanlon AL, Troncoso P, Al-Saleem T, Horowitz EM, Pollack A. The Gleason score shift: score four and seven years ago. Int. J. Radiat. Oncol. Biol. Phys. 2003; 56; 1241–1247.

- Kondylis FI, Moriarty RP, Bostwick D, Schellhammer P. Prostate cancer grade assignment: the effect of chronological, interpretative and translation bias. J. Urol. 2003; 170; 1189–1193.

- Albertsen PC, Hanley JA, Barrows GH et al. Prostate cancer and the Will Rogers phenomenon. J. Natl Cancer Inst. 2005; 97; 1248–1253.

- Helpap B, Egevad L. The significance of modified Gleason grading of prostatic carcinoma on biopsy and radical prostatectomy specimens. Vichows Arch. 2006; 449; 622–627.

- Billis A, Guimaraes MS, Freitas LL, Meirelles L, Magna LA, Fereira U. The impact of the 2005 International Society of Urological Pathology consensus conference on standard Gleason grading of prostatic carcinoma in needle biopsies. J. Urol. 2008; 180; 548–552.

- Lin KK. Pathologic findings in 5912 prostate biopsies. [Abstract.] Mod. Pathol. 2008; 21 (Suppl. 1); 166A.

- Gofrit ON, Zorn KC, Steinberg GD, Zagaja GP, Shalhav AL. The Will Rogers phenomenon in urological oncology. J. Urol. 2008; 179; 28–33.

- Feinstein AR, Sosin DM, Wells CK. The Will Rogers phenomenon: stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. New Engl. J. Med. 1985; 312; 1604–1608.

Regards,
Greg_L-W.

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Hi,

Prostate Cancer: Stages and Grades

Approved by the Cancer.Net Editorial Board, 01/2017

ON THIS PAGE: You will learn about how doctors describe a cancer’s growth or spread, as well as what the cancer cells look like under a microscope. This is called the stage and grade. To see other pages, use the menu.

Staging is a way of describing where the cancer is located, if or where it has spread, and whether it is affecting other parts of the body.

Doctors use diagnostic tests to find out the cancer’s stage, so staging may not be complete until all of the tests are finished. Staging for prostate cancer also involves looking at test results to find out if the cancer has spread from the prostate to other parts of the body. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient’s prognosis, which is the chance of recovery. There are different stage descriptions for different types of cancer.

There are 2 types of staging for prostate cancer:

  • The clinical stage is based on the results of tests done before surgery, which includes DRE, biopsy, x-rays, CT and/or MRI scans, and bone scans. X-rays, bone scans, CT scans, and MRI scans may not always be needed. They are recommended based on the PSA level; the size of the cancer, which includes its grade and volume; and the clinical stage of the cancer.
  • The pathologic stage is based on information found during surgery, plus the laboratory results, referred to as pathology, of the prostate tissue removed during surgery. The surgery often includes the removal of the entire prostate and some lymph nodes.

TNM staging system

One tool that doctors use to describe the stage is the TNM system. Doctors use the results from diagnostic tests and scans to answer these questions:

  • Tumor (T): How large is the primary tumor? Where is it located?
  • Node (N): Has the tumor spread to the lymph nodes? If so, where and how many?
  • Metastasis (M): Has the cancer metastasized to other parts of the body? If so, where and how much?

The results are combined to determine the stage of cancer for each person. There are 5 stages: stage 0 (zero) and stages I through IV (1 through 4). The stage provides a common way of describing the cancer, so doctors can work together to plan the best treatments.

Here are more details about each part of the TNM system for prostate cancer.

Tumor (T)

Using the TNM system, the “T” plus a letter or number (0 to 4) is used to describe the size and location of the tumor. Some stages are also divided into smaller groups that help describe the tumor in even more detail. Specific tumor stage information is listed below.

TX: The primary tumor cannot be evaluated.

T0 (T plus zero): There is no evidence of a tumor in the prostate.

T1: The tumor cannot be felt during a DRE and is not seen during imaging tests. It may be found when surgery is done for another reason, usually for BPH or an abnormal growth of noncancerous prostate cells.

  • T1a: The tumor is in 5% or less of the prostate tissue removed during surgery.
  • T1b: The tumor is in more than 5% of the prostate tissue removed during surgery.
  • T1c: The tumor is found during a needle biopsy, usually because the patient has an elevated PSA level.

T2: The tumor is found only in the prostate, not other parts of the body. It is large enough to be felt during a DRE.

  • T2a: The tumor involves one-half of 1 lobe (part or side) of the prostate.
  • T2b: The tumor involves more than one-half of 1 lobe of the prostate but not both lobes.
  • T2c: The tumor has grown into both lobes of the prostate.

T3: The tumor has grown through the prostate capsule on 1 side and into the tissue just outside the prostate.

  • T3a: The tumor has grown through the prostate capsule either on 1 side or on both sides of the prostate, or it has spread to the neck of the bladder. This is also known as an extraprostatic extension (EPE).
  • T3b: The tumor has grown into the seminal vesicle(s), the tube(s) that carry semen.

T4: The tumor is fixed, or it is growing into nearby structures other than the seminal vesicles, such as the external sphincter, the part of the muscle layer that helps to control urination; the rectum; levator muscles; or the pelvic wall.

Node (N)

The “N” in the TNM staging system stands for lymph nodes. These tiny, bean-shaped organs help fight infection. Lymph nodes near the prostate in the pelvic region are called regional lymph nodes. Lymph nodes in other parts of the body are called distant lymph nodes.

NX: The regional lymph nodes cannot be evaluated.

N0 (N plus zero): The cancer has not spread to the regional lymph nodes.

N1: The cancer has spread to the regional (pelvic) lymph node(s).

Metastasis (M)

The “M” in the TNM system indicates whether the prostate cancer has spread to other parts of the body, such as the lungs or the bones. This is called distant metastasis.

MX: Distant metastasis cannot be evaluated.

M0 (M plus zero): The disease has not metastasized.

M1: There is distant metastasis.

  • M1a: The cancer has spread to nonregional, or distant, lymph node(s).
  • M1b: The cancer has spread to the bones.
  • M1c: The cancer has spread to another part of the body, with or without spread to the bone.

Cancer stage grouping

Doctors assign the stage of the cancer by combining the T, N, and M classification. See the table below the stage descriptions for all of the TNM combinations for each stage.

Stage I: Cancer is found in the prostate only, usually during another medical procedure. It cannot be felt during the DRE or seen on imaging tests. A stage I cancer is usually made up of cells that look more like healthy cells and is usually slow growing. 

Stage I Prostate Cancer

Stage IIA and IIB: This stage describes a tumor that is too small to be felt or seen on imaging tests. Or, it describes a slightly larger tumor that can be felt during a DRE. The cancer has not spread outside of the prostate gland, but the cells are usually more abnormal and may tend to grow more quickly. A stage II cancer has not spread to lymph nodes or distant organs. 

Stage IIA Prostate Cancer

Stage IIB Prostate Cancer

Stage III: The cancer has spread beyond the outer layer of the prostate into nearby tissues. It may also have spread to the seminal vesicles. 

Stage I Prostate Cancer

Stage IV: This stage describes any tumor that has spread to other parts of the body, such as the bladder, rectum, bone, liver, lungs, or lymph nodes. 

Stage IV Prostate Cancer

Recurrent: Recurrent prostate cancer is cancer that has come back after treatment. It may come back in the prostate area again or in other parts of the body. If the cancer does return, there will be another round of tests to learn about the extent of the recurrence. These tests and scans are often similar to those done at the time of the original diagnosis.

Stage Grouping Chart

Stage

T

N

M

I

T1a, T1b, or T1c

N0

M0

 

T2a

N0

M0

 

Any T1 or T2a

N0

M0

 

 

 

 

IIA

T1a, T1b, or T1c

N0

M0

 

T1a, T1b, or T1c

N0

M0

 

T2a

N0

M0

 

T2b

N0

M0

 

T2b

N0

M0

 

 

 

 

IIB

T2c

N0

M0

 

Any T1 or T2

N0

M0

 

Any T1 or T2

N0

M0

 

 

 

 

III

T3a or T3b

N0

M0

 

 

 

 

 

 

 

 

IV

T4

N0

M0

 

Any T

N1

M0

 

Any T

Any N

M1

Used with permission of the AJCC, Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition, published by Springer-Verlag New York, www.cancerstaging.org

Gleason score for grading prostate cancer

Prostate cancer is also given a grade called a Gleason score. This score is based on how much the cancer looks like healthy tissue when viewed under a microscope. Less aggressive tumors generally look more like healthy tissue. Tumors that are more aggressive are likely to grow and spread to other parts of the body. They look less like healthy tissue.

The Gleason scoring system is the most common prostate cancer grading system used. The pathologist looks at how the cancer cells are arranged in the prostate and assigns a score on a scale of 1 to 5. Cancer cells that look similar to healthy cells receive a low score. Cancer cells that look less like healthy cells or look more aggressive receive a higher score. To assign the numbers, the doctor determines the main pattern of cell growth, which is the area where the cancer is most obvious; looks for any other less common pattern of growth; and gives each 1 a score. The scores are added together to come up with an overall score between 2 and 10.

The interpretation of the Gleason score by doctors has changed recently. Originally, doctors used a wide range of scores. Today, doctors no longer use Gleason scores of 5 or lower for cancer found with a biopsy. The lowest score used is 6, which is a low-grade cancer. A Gleason score of 7 is a medium-grade cancer, and a score of 8, 9, or 10 is a high-grade cancer. A lower-grade cancer grows more slowly and is less likely to spread than a high-grade cancer.

Doctors look at the Gleason score in addition to stage to help plan treatment. For example, active surveillance, described in the Treatment Options section, may be an option for a patient with a small tumor, low PSA level, and a Gleason score of 6. Patients with high Gleason score may need treatment that is more intensive, even if it does not appear that the cancer has spread.

Gleason X: The Gleason score cannot be determined.

Gleason 6 or lower: The cells are well differentiated, meaning they look similar to healthy cells.

Gleason 7: The cells are moderately differentiated, meaning they look somewhat similar to healthy cells.

Gleason 8, 9, or 10: The cells are poorly differentiated or undifferentiated, meaning they look very different from healthy cells.

Recently, pathologists have begun to adopt a new Gleason grouping system that arranges the scores into simplified groups that are translated as follows:

  • Gleason Group I = Former Gleason 6
  • Gleason Group II = Former Gleason 3 + 4 = 7
  • Gleason Group III = Former Gleason 4 + 3 = 7
  • Gleason Group IV = Former Gleason 8
  • Gleason Group V = Former Gleason 9 or 10

Prostate Cancer Risk Groups

In addition to stage, doctors use other prognostic factors to help plan the best treatment and predict how successful treatment will be. Two such risk assessment methods come from the National Comprehensive Cancer Network (NCCN) and the University of California, San Francisco (UCSF).

NCCN

The NCCN developed 4 risk-group categories based on PSA level, prostate size, needle biopsy findings, and the stage of cancer. The lower your risk, the lower the chance that the prostate cancer will grow and spread.

  • Very low risk. The tumor cannot be felt during a DRE and is not seen during imaging tests but was found during a needle biopsy (T1c). PSA is less than 10 ng/mL. The Gleason score is 6 or less. Cancer was found in fewer than 3 samples taken during a core biopsy. The cancer was found in half or less of any core.
  • Low risk. The tumor is classified as T1a, T1b, T1c, or T2a (see above). PSA is less than 10 ng/mL. The Gleason score is 6 or less.
  • Intermediate risk. The tumor has 2 or more of these characteristics:
    • Classified as T2b or T2c (see above)
    • PSA is between 10 and 20 ng/mL
    • Gleason score of 7
  • High risk. The tumor has 2 or more of these characteristics:
    • Classified as T3a (see above)
    • PSA level is higher than 20 ng/mL
    • Gleason score is between 8 and 10
  • Very high risk. The tumor is classified as T3b or T4 (see above). The histologic grade is 5 for the main pattern of cell growth, or more than 4 biopsy cores have Gleason scores between 8 and 10.

Source: Risk group information is adapted from the NCCN.

UCSF Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score

The UCSF-CAPRA score predicts a man’s chances of having the cancer spread and of dying. This score can be used to help make decisions about the treatment plan. Points are assigned according to a person’s age at diagnosis, PSA at diagnosis, Gleason score of the biopsy, T classification from the TNM system, and the percentage of biopsy cores involved with cancer. These categories are then used to assign a score between 0 and 10.

  • CAPRA score 0 to 2 indicates low risk.
  • CAPRA score 3 to 5 indicates intermediate risk.
  • CAPRA score 6 to 10 indicates high risk.   

Information about the cancer’s stage and other prognostic factors will help the doctor recommend a specific treatment plan. The next section in this guide is Treatment Options. Or, use the menu to choose another section to continue reading this guide.

To view the original of this article CLICK HERE
 

Regards,
Greg_L-W.

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Posted by: Greg Lance-Watkins
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  14. I AM strongly opposed to the subsidy or use of failed technologies eg. WIND TURBINES
  15. I AM IN FAVOUR of rapid research & development of NEW NUCLEAR technologies
  16. I see no evidence to trust POLITICIANS at any level or of any persuasion
  17. I do NOT believe in GODS singular or plural, Bronze Age or Modern
  18. I value the NHS as a HEALTH SERVICE NOT a Lifestyle support
  19. I believe in a DEATH PENALTY for serial or GBH rape.
  20. I believe in a DEATH PENALTY for serial, terrorist, mass or for pleasure murder.
  21. I believe in a DEATH PENALTY for serial gross child abuse including sexual.
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Getting Prostate Gland Test results

Getting Prostate Gland Test results

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Getting Prostate Gland Test results

It usually takes around two weeks to get all the results.
These can give an indication of how far the cancer has spread and how quickly it might be growing.

If your PSA (Prostate Specific Antogen) test shows that you have a high PSA level for your age, this could be a sign of prostate cancer, but it can also be caused by other things.

If your DRE (Digital Rectal Examination) shows that your prostate is larger than expected this could be a sign of an enlarged prostate. A prostate with hard, bumpy areas may suggest prostate cancer.
If your biopsy shows there is cancer present, the results are used to work out your Gleason score.
This can give an idea of how likely the cancer is to spread.
The results of any scans you might have had will help to stage your cancer to show how far the cancer might have spread.
Contents:
Gleason score
Staging
Localised prostate cancer
Locally advanced prostate cancer
Advanced prostate cancer
What happens next?
Rare types of prostate cancer
Questions to ask your doctor or nurse
Gleason grade
If there are prostate cancer cells in your biopsy samples, they are given a Gleason grade. This tells you how aggressive the cancer is – which means how likely it is to grow and spread outside the prostate.

When cancer cells are looked at under the microscope, they have different patterns, depending on how quickly they are likely to grow. The pattern is given a grade from 1 to 5. This is called the Gleason grade. If a grade is given, it will usually be 3 or higher, as grade 1 and 2 are not cancer.

Gleason score
There may be more than one grade of cancer in the biopsy samples. An overall Gleason score is worked out by adding together two Gleason grades.

The first is the most common grade in all the samples. The second is the highest grade of what’s left. When the most common and the highest grade are added together, the total is called the Gleason score.

For example, if the biopsy samples show that:

most of the cancer seen is grade 3 and
the highest grade of any other cancer seen is grade 4, then
the Gleason score will be 7 (3+4).
Because grade 1 and 2 are not cancer, the combined Gleason score is normally 6 or higher. So your Gleason score can normally only be between 6 (3+3) and 10 (5+5).

Some men will only be told their total Gleason score and not given their Gleason grades.

What does the Gleason score mean?

The higher the Gleason score, the more aggressive the cancer and the more likely it is to spread.

3+3 – All of the cancer cells found in the biopsy look likely to grow slowly.
3+4 – Most of the cancer cells found in the biopsy look likely to grow slowly. There were some cancer cells that look more likely to grow at a more moderate rate.
4+3 – Most of the cancer cells found in the biopsy look likely to grow at a moderate rate. There were some cancer cells that look likely to grow slowly.
4+4 – All of the cancer cells found in the biopsy look likely to grow at a moderately quick rate.
4+5 – Most of the cancer cells found in the biopsy look likely to grow at a moderately quick rate. There were some cancer cells that are likely to grow more quickly.
5+4 – Most of the cancer cells found in the biopsy look likely to grow quickly.
5+5 – All of the cancer cells found in the biopsy look likely to grow quickly.
Your doctor or nurse will talk you through what your results mean.

Back to contents

Staging
Staging is a way of recording how far the cancer has spread. The most common method is the TNM (Tumour Nodes Metastases) system.

The T stage measures the tumour.
The N stage measures whether the cancer has spread to the lymph nodes.
The M stage measures whether the cancer has spread (metastasised) to other parts of the body.
T Stage

The T stage shows how far the cancer has spread in and around the prostate. This is measured by a DRE. You may also have an MRI scan to confirm your T stage.

T1 prostate cancer
The cancer can’t be felt or seen on scans, and can only be seen under a microscope – localised prostate cancer.

T1 prostate cancer
T1 prostate cancer

T2 prostate cancer
The cancer can be felt or seen on scans, but it is contained within the prostate – localised prostate cancer.

T2 Prostate Cancer
T2 Prostate Cancer

T3 prostate cancer
The cancer can be felt or seen breaking through the capsule of the prostate – locally advanced prostate cancer.

T3a The cancer has broken through the capsule of the prostate but has not spread to the seminal vesicles (which produce some of the fluid in semen).
T3b The cancer has spread to the seminal vesicles.
T3 Prostate Cancer
T3 Prostate Cancer

T4 prostate cancer
The tumour has spread to nearby organs, such as the neck of the bladder, back passage, pelvic wall or lymph nodes – locally advanced prostate cancer.

T4 Prostate CancerN Stage

T4 Prostate Cancer

The N stage shows whether the cancer has spread to the nearby lymph nodes. The lymph nodes in the groin are a common place for prostate cancer to spread to. They are looked at with an MRI or CT scan.

You may be offered one of these scans if you’re thinking about having a treatment such as radiotherapy or surgery and there is a risk that your cancer might have spread to your lymph nodes.

NX The lymph nodes were not measured.
N0 No cancer cells can be seen in the lymph nodes.
N1 The lymph nodes contain cancer cells.
If your scans suggest that your cancer has spread to the lymph nodes (N1), it may either be treated as locally advanced or advanced prostate cancer. This may depend on several things, such as how far it has spread (M stage).

M Stage

The M stage shows whether the cancer has spread (metastasised) to other parts of the body, such as the bones. This is measured using a bone scan.

Your doctor may offer you a bone scan if they think your cancer may have spread.

MX The spread of the cancer was not measured.
M0 The cancer has not spread to other parts of the body.
M1 The cancer has spread to other parts of the body.
If you have a bone scan and the results show that your cancer has spread to other parts of the body (M1), you will be diagnosed with advanced prostate cancer.

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Localised prostate cancer
Localised prostate cancer is cancer that is contained within the prostate gland. It is also called early or organ-confined prostate cancer.

Prostate cancer can behave in different ways. Many localised cancers are not aggressive and will not cause any problems in your lifetime. However, some cancers may grow more quickly and spread to other parts of the body.

The tests you have had can give your doctor and idea of how the cancer will behave and what treatments may be suitable for you.

What is the chance my cancer will spread?

Doctors often divide localised prostate cancers into risk groups. This is the risk of the cancer coming back after treatment. This is used to help decide which treatment options are suitable for you.

Low risk

your PSA level is 10ng/ml or less, and
your Gleason score is 6 or less, and
the stage of your cancer is T1 to T2a
Medium risk

your PSA level is between 10 and 20ng/ml, or
your Gleason score is 7, or
the stage of your cancer is T2b or T2c
High risk

your PSA level is 20 ng/ml or higher, or
your Gleason score is 8 or higher, or
the stage of your cancer is T3 or T4.
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Locally advanced prostate cancer
Locally advanced prostate cancer is cancer that is breaking through the capsule of the prostate, or has spread to the area just outside the prostate. This can include the seminal vesicles, lymph nodes, neck of the bladder or back passage.

Different doctors sometimes use the term “locally advanced prostate cancer” in slightly different ways, so ask your doctor or nurse what it means in your case.

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Advanced prostate cancer
Advanced prostate cancer is cancer that has spread from the prostate gland to other parts of the body. It is also called ‘metastatic’ prostate cancer. It develops when tiny prostate cancer cells move from the prostate to other parts of the body through the blood stream or lymphatic system.

Prostate cancer can spread to any part of the body but it most commonly spreads to the bones and the lymph nodes.

Advanced prostate cancer can cause symptoms, which may be the first sign that something is wrong for some men. Symptoms will depend on where the cancer has spread to, but can include bone pain or problems passing urine. Not all men diagnosed with advanced prostate cancer will have symptoms.

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What happens next?
The results will give your multi-disciplinary team (MDT) an idea of how your cancer is behaving and the most suitable treatment options for you.

If you are not sure whether your prostate cancer is localised, locally advanced or advanced, speak to your doctor or nurse. They can explain your test results and talk to you about your treatment options. Or you can call our Specialist Nurses. You can also request a second opinion from another specialist by talking to your GP.

It can be hard to take everything in, especially when you’ve just been diagnosed with prostate cancer. You might find it useful to have someone with you at the consultation, or to make notes so that you can read them in your own time. There is also support available.

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Rare types of prostate cancer
As well as giving the Gleason score, a biopsy also looks at the type of cancer cells. For most men who are diagnosed, the type of prostate cancer is adenocarcinoma, or acinar adenocarcinoma. You might see this written on your pathology report. There are other types of prostate cancer, which are very rare. These include:

small cell prostate cancer (neuroendocrine prostate cancer)
large cell prostate cancer (neuroendocrine prostate cancer)
ductal prostate cancer (ductal adenocarcinoma)
mucinous prostate cancer (mucinous adenocarcinoma)
signet ring cell prostate cancer
basal cell prostate cancer (adenoid cystic prostate cancer)
prostate sarcomas, such as leiomyosarcoma.
If you are diagnosed with one of these rare kinds of prostate cancer, you can read more here. Speak to your doctor or nurse about what it means and about the treatments available to you.

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Questions to ask your doctor or nurse
What is my PSA level?
Will I need a biopsy? What type of biopsy will I have?
What are the risks and side effects of having a biopsy?
What are my Gleason grades and Gleason score?
Will I need an MRI, CT or bone scan?
What is the stage of my cancer? What does this mean?
What treatments are suitable for me?

To view the original of this article CLICK HERE
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Regards,
Greg_L-W.
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 Please Be Sure To
& Link to my My Blogs
To Spread The Facts World Wide To Give Others HOPE
I Have Been Fighting Cancer since 1997 & I’M STILL HERE!
I Have Cancer, Cancer Does NOT Have Me
I just want to say sorry for copping out at times and leaving Lee and friends to cope!
Any help and support YOU can give her will be hugely welcome.
I do make a lousy patient!

.
If YOU want to follow my fight against Cancer from when it started and I first presented with symptoms in 1998 see The TAB at the Header of this Blog. called >DIARY of Cancer ….< just click and it will give you a long list of the main events in chronological order, many linked to specific blog postings.
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Thoughts, articles and comments will be in chronological order in the main blog and can be tracked in the >ARCHIVE< in the Left Sidebar.
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You may find the TABS >MEDICAL LINKS< and also >CANCER LINKS< of help, also many of the links in articles and >HOT LINKS< in the Sidebar.
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YOU are welcome to call me, minded that I am NOT medically trained, if you believe I can help in ANY way. .

Posted by: Greg Lance-Watkins

tel: 01594 – 528 337
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Women Can Help Men Spot Prostate Cancer

Women Can Help Men Spot Prostate Cancer
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How women can help men spot symptoms of prostate cancer

How to spot the symptoms of prostate cancer
As male patients are being given false hope on prostate cancer, Louisa Peacock outlines how wives and girlfriends can help their male partners spot the disease.
How to spot the symptoms of prostate cancer
How to spot the symptoms of prostate cancer Photo: Wellcome Collection
Louisa Peacock By Louisa Peacock2:01PM BST 11 Apr 2014
Prostate cancer is very tricky to spot, according to the charity Prostate Cancer UK. In some cases, the symptoms may develop over a number of years. In other patients, by the time symptoms become noticeable, prostate cancer has already spread to their bones.
Most men with early prostate cancer do not have symptoms, the charity points out.
However, there are some warning signs for men, and as a recent study showed, because men routinely risk their health by failing to go and see the doctor, their partners can often encourage them to go and get symptoms checked before it’s too late.
Symptoms to look out for:
– Having to get up in the night several times to empty your bladder, which you wouldn’t normally do
– Having trouble starting to urinate
Related Articles
Half of prostate cancer cases may be missed 14 Jun 2013
Anger over NHS ‘U-turn’ on prostate cancer drugs 28 Jan 2014
Men with prostate cancer ‘falsely’ told it is not aggressive 11 Apr 2014
Why do men still need women to make them visit the doctor? 05 Nov 2012
UK men ‘losers in European prostate cancer lottery’ 07 Mar 2013

– Feeling as though the bladder isn’t emptying properly
– Dribbling after urinating

In the above video from Prostate Cancer UK, John Robertson, a prostate cancer specialist nurse, explains that the symptoms may be linked to bladder problems, or an enlarged prostate. In some cases, they can be due to prostate cancer and it’s best to get this checked by a GP.

Fear of the doctor
A recent study by the National Pharmacy Association showed that nearly nine in 10 men don’t like to trouble a doctor unless they have a “serious problem”. This reticence has largely been attributed to men’s fear of the doctor, (white coat syndrome) and male machismo.
Partners, wives or girlfriends of men should encourage their loved one to get checked if they notice any unusual bathroom habits.
Historically, women have usually been the custodians of health in the family. Mums, grandmothers, sisters, aunts – have typically been the ones to make their men visit health professionals and sort any kind of ill health out proactively.
Women can help men quell the irrational fear of going to the doctor, so they can seek help before it’s too late.
Where prostate cancer has already spread to the bones, the symptoms can include long standing pain in one area, such as the back or pelvic bones.
However, Mr Robertson points out this could be a sign of another illness, such as arthritis.
Blood in semen or in urine could indicate prostate or urine infection, or prostate cancer, he adds. Either way, you’re advised to check it out.
To view the original article CLICK HERE
If you are unsure and want some advice on prostate cancer, talk to a specialist nurse at the Prostate Cancer UK charity on 0800 074 8383 or visit the website at prostatecanceruk.org
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Regards,
Greg_L-W.
.
 Please Be Sure To
& Link to my My Blogs
To Spread The Facts World Wide To Give Others HOPE
I Have Been Fighting Cancer since 1997 & I’M STILL HERE!
I Have Cancer, Cancer Does NOT Have Me
I just want to say sorry for copping out at times and leaving Lee and friends to cope!
Any help and support YOU can give her will be hugely welcome.
I do make a lousy patient!

.
If YOU want to follow my fight against Cancer from when it started and I first presented with symptoms in 1998 see The TAB at the Header of this Blog. called >DIARY of Cancer ….< just click and it will give you a long list of the main events in chronological order, many linked to specific blog postings.
.
Thoughts, articles and comments will be in chronological order in the main blog and can be tracked in the >ARCHIVE< in the Left Sidebar.
.
You may find the TABS >MEDICAL LINKS< and also >CANCER LINKS< of help, also many of the links in articles and >HOT LINKS< in the Sidebar.
.
YOU are welcome to call me, minded that I am NOT medically trained, if you believe I can help in ANY way. .

Posted by: Greg Lance-Watkins

tel: 01594 – 528 337
Accuracy & Copyright Statement: CLICK HERE
Summary, archive, facts & comments on UKIP: http://UKIP-vs-EUkip.com
DO MAKE USE of LINKS & >Right Side Bar< & The Top Bar >PAGES<
Also:
Details & Links: http://GregLanceWatkins.com
UKIP Its ASSOCIATES & DETAILS: CLICK HERE
Views I almost Totally Share: CLICK HERE
General Stuff archive: http://gl-w.blogspot.com
General Stuff ongoing: http://gl-w.com
Health Blog. Archive: http://GregLW.blogspot.com
Health Blog. Ongoing: http:GregLW.com

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Degaralix Joins The Armoury For Metastasised Prostate Cancer

Degaralix Joins The Armoury For Metastasised Prostate Cancer

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NICE approves drug for advanced prostate cancer for use on the NHS
15 Apr 2014
A drug which could improve the quality of life for men whose prostate cancer has spread to the spine has today (15 April 2014) been approved to be made available on the NHS in England and Wales by the National Institute for Health and Care Excellence (NICE).The drug, degarelix, is a form of hormone therapy which is delivered by injection. NICE has recommended that the drug be made available to men with prostate cancer which has metastasised to the spine and who are showing signs or symptoms of spinal cord compression. Men who have been diagnosed with advanced prostate cancer may experience pain as a result of the disease spreading throughout the body. If this spread affects the spine, there is a risk of spinal cord compression which can cause problems such as back pain and other symptoms in the legs, bladder or bowel. Reducing the body’s production of testosterone can help keep a man’s prostate cancer under control for some time, however some hormone therapies can cause initial testosterone surges which could lead to flare ups of these existing problems. Degarelix can rapidly suppress testosterone production, but has a lower risk of these testosterone surges compared to other similar treatments.

Degarelix has already been approved for use in this way on the NHS in Scotland by the Scottish Medicines Consortium.

Mikis Euripides, Director of Policy at Prostate Cancer UK said:

“Men whose prostate cancer has spread to the spine are often at risk of even further damage through spinal cord compression and if left untreated this could be crippling. We fought to make this drug available and so this decision is good news which could help dramatically improve the quality of life of those men. However, whilst we welcome this positive outcome, the ruling will affect far fewer men than those currently in limbo waiting to hear whether NICE will deny them access to the life-extending drug enzalutamide.

We will continue to campaign to ensure that men with prostate cancer have access to the best treatments, not least enzalutamide.”

To view the original of this article CLICK HERE
.
Regards,
Greg_L-W.
.
 Please Be Sure To
& Link to my My Blogs
To Spread The Facts World Wide To Give Others HOPE
I Have Been Fighting Cancer since 1997 & I’M STILL HERE!
I Have Cancer, Cancer Does NOT Have Me
I just want to say sorry for copping out at times and leaving Lee and friends to cope!
Any help and support YOU can give her will be hugely welcome.
I do make a lousy patient!

.
If YOU want to follow my fight against Cancer from when it started and I first presented with symptoms in 1998 see The TAB at the Header of this Blog. called >DIARY of Cancer ….< just click and it will give you a long list of the main events in chronological order, many linked to specific blog postings.
.
Thoughts, articles and comments will be in chronological order in the main blog and can be tracked in the >ARCHIVE< in the Left Sidebar.
.
You may find the TABS >MEDICAL LINKS< and also >CANCER LINKS< of help, also many of the links in articles and >HOT LINKS< in the Sidebar.
.
YOU are welcome to call me, minded that I am NOT medically trained, if you believe I can help in ANY way. .

Posted by: Greg Lance-Watkins

tel: 01594 – 528 337
Accuracy & Copyright Statement: CLICK HERE
Summary, archive, facts & comments on UKIP: http://UKIP-vs-EUkip.com
DO MAKE USE of LINKS & >Right Side Bar< & The Top Bar >PAGES<
Also:
Details & Links: http://GregLanceWatkins.com
UKIP Its ASSOCIATES & DETAILS: CLICK HERE
Views I almost Totally Share: CLICK HERE
General Stuff archive: http://gl-w.blogspot.com
General Stuff ongoing: http://gl-w.com
Health Blog. Archive: http://GregLW.blogspot.com
Health Blog. Ongoing: http:GregLW.com

TWITTER: Greg_LW

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PROSTATE CANCER, Treat? Cut? or Ignore?

PROSTATE CANCER, Treat? Cut? or Ignore?
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To Treat or Not to Treat Prostate Cancer: That Is the Question

January 18, 2012

By Durado Brooks, MD, MPH

Imagine being told by your doctor, “You have cancer.”  Then imagine that their next words are “… but we probably don’t need to do anything about it.”  Many people would immediately start looking for another doctor. But hold on just a moment.
Last month the National Institutes of Health (NIH) brought together experts from around the world for a summit to examine the state of our scientific knowledge on “active surveillance” as a management strategy for prostate cancer. For those of you who are unfamiliar with the term, active surveillance essentially means monitoring the cancer closely and delaying active treatment (surgery or radiation, for instance) until there are signs it is needed; the delay may be months, years, or forever. This summit pointed out that while there is still much we need to learn about this once-controversial approach, there is a wealth of data supporting the potential value of active surveillance for a large number of the 240,000 men in the United States who are diagnosed with prostate cancer each year. 
Not treating cancer?
To most individuals, the idea of having cancer and choosing not to treat it smacks of fatalism, or just giving up. In order to understand why this is not the case, it is important to appreciate that all prostate cancers are not created equal. 
There are many prostate cancers that can be singled out as likely to be slow growing and posing a low risk to the affected man;  these can be identified by looking at a man’s PSA level (prostate specific antigen; a protein made by the prostate gland and measured in the blood), Gleason score (a numerical representation of how a man’s tumor looks under the microscope), and other factors (size of the tumor, how much of the prostate gland is invaded by cancer, etc.). The vast majority of men with these low-risk tumors will end up dying of something other than prostate cancer, and few of these men would ever experience any harm from their cancer if it went untreated (or if it was never found in the first place).  
It’s estimated that as many as half of the prostate cancers diagnosed each year in the US fit into this low-risk category. However, to most people the term “low-risk cancer” sounds like an oxymoron.  This quandary prompted a number of summit speakers to question whether this type of tumor should even be called “cancer,” or if the scientific community should come up with a new, less frightening term to describe these slow growing prostate lesions.  
For most men who are told that they have prostate cancer the first question is, “How soon can we get rid of it?” In the US, 90% of these men move very rapidly to what is viewed as definitive therapy, usually prostatectomy (surgical removal of the prostate gland) or killing the cancer cells with radiation treatment. These treatments come with the risk of side effects and complications, most commonly damage to bladder or bowel function, and sexual difficulties.  A recent report from the US Preventive Services Task Force estimates that 1 or more of these complications occur in up to 30 of every 100 men treated for prostate cancer; the same report indicates that 1 of every 200 men who undergo surgical removal of their prostate dies within 30 days of their surgery.  These numbers point to why it’s so important to explore alternative approaches to managing this disease.

Watchful waiting and active surveillance

Prostate cancer is primarily a disease of older men, and many men diagnosed with the disease already have multiple health problems (and in some cases a limited life expectancy).  Given these circumstances it has long been the practice of doctors who treat prostate cancer to weigh these factors and to recommend to some men that, as opposed to beginning treatment shortly after diagnosis, they be observed by their doctors and begin treatment only if they develop symptoms that suggest that their cancer is getting worse.  This approach is known as “watchful waiting.”

Over time, evidence emerged that most men who were observed in this fashion did well for a number of years.  This information, combined with the growing number of low-risk tumors being diagnosed as a result of having widespread PSA screening for prostate cancer, raised the question as to whether younger, healthy men might also benefit from a delayed treatment approach. 

Managing the cancer in these men evolved from simple observation to more intensive follow up, including repeated PSA tests and regular biopsies of the prostate gland, treating the cancer only if it begins to grow or spread. This approach has become known as “active surveillance” (differentiating it from the more passive watchful waiting).  Research studies were undertaken to find out about the impact of both of these approaches on the long-term outcomes of men with prostate cancer, and speakers at the NIH summit described findings from a number of such studies.


‘A viable option’ for low-risk patients
In one of these studies, the Prostate Cancer Intervention vs. Observation Trial (PIVOT), men diagnosed with low-risk prostate cancer were given the option of prostatectomy or observation; these men were then tracked over time. PIVOT used a traditional watchful waiting approach: men were simply observed and treatment was begun only if symptoms developed or if the man requested it.  After approximately 10 years of follow up the risk of dying from prostate cancer was small (less than 10%), and was essentially the same whether a man chose surgery or observation.  The risk of death from any cause, including both prostate cancer and other diseases (referred to as “all cause mortality”) was also about the same between these groups. 
A number of other studies have been carried out to look at outcomes of active surveillance, using observation combined with repeat PSA tests and prostate biopsies to look for whether the cancer was spreading or getting worse. These studies, some of which have been underway for 15 years or more, have found that only a small proportion of men diagnosed with low-risk disease will show signs of significant cancer progression. 
Like PIVOT, most active surveillance studies have found low rates of death from prostate cancer among men with low-risk disease. They have also found similar rates of all cause mortality in men who choose active surveillance when compared to men who got immediate treatment. In addition, men who choose an observational approach (active surveillance or watchful waiting) avoid or delay the side effects associated with surgery or radiation. Based on the strength of the accumulated evidence the NIH expert panel concluded that “active surveillance has emerged as a viable option that should be offered to all low-risk patients.”

Bottom line
So why do 9 out of 10 men with prostate cancer in the US end up being treated shortly after they’re diagnosed? It turns out that many prostate cancer patients have never heard of active surveillance or watchful waiting, and are never told that observation is an option they could consider for their cancer. In other cases active surveillance is discussed as a potential management option but is presented in an unfavorable manner (i.e., “we can treat your cancer or we can just do nothing”). 
Even in circumstances where active surveillance is discussed in a fair, objective manner there are a number of other factors that may influence the likelihood of men choosing and sticking with this option.  These include whether or not their physician supports their choice, support from family and friends, and the patients’ personal perceptions of and experience with cancer (whether they themselves have had other types of cancer in the past, or observed friends or family go through cancer treatment).
So if you or someone close to you has been diagnosed with prostate cancer – slow down! After getting past the shock, start asking some questions. Find out all that you can about the tumor, and determine whether the cancer fits into the low-risk category. Be sure to explore all treatment options, including active surveillance. In some cases of prostate cancer “no treatment” may turn out to be the best treatment.

Ti view the original article CLICK HERE

The NIH expert panel draft report can be accessed at http://consensus.nih.gov/2011/prostate.htm.

Brooks is director of prostate and colorectal cancers for the American Cancer Society.

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 Please Be Sure To
My Blogs
To Spread The Facts World Wide To Give Others HOPE
I Have Been Fighting Cancer since 1997 & I’M STILL HERE!
I Have Cancer, Cancer Does NOT Have Me
I just want to say sorry for copping out at times and leaving Lee and friends to cope!
Any help and support YOU can give her will be hugely welcome.
I do make a lousy patient!

.
If YOU want to follow my fight against Cancer from when it started and I first presented with symptoms see The TAB just below the Header of this Blog. called >DIARY of Cancer< just click and it will give you a long list of the main events in chronological order.
.
Thoughts and comments will be in chronological order in the main blog and can be tracked in the >ARCHIVE< in the Right Sidebar.

You may find the TABS >MEDICAL LINKS< and also >CANCER LINKS< of help.
.
YOU are welcome to call me if you believe I can help in ANY way.
.

Posted by: Greg Lance-Watkins
tel: 01594 – 528 337
DO MAKE USE of LINKS & >Right Side Bar< Also:
General Stuff: http://gl-w.blogspot.com  
  TWITTER: Greg_L
  
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PROSTATE CANCER – Can Cancer Ever Be Ignored?

PROSTATE CANCER – Can Cancer Ever Be Ignored? 

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Can Cancer Ever Be Ignored?

  • As chief medical and scientific officer of the American Cancer SocietyOtis Webb Brawley — who is also a professor of oncology and epidemiology at Emory University — is the public face of the cancer establishment. He operates in a world of similarly high-achieving, multiple-credentialed, respectable professionals, where insults tend to be delivered, stiletto-style, in scientific language that lay people aren’t meant to understand. So it can be more than a little jarring to hear, for example, James Mohler, chairman of the urology department and associate director of the Roswell Park Cancer Institute in Buffalo, say of his friend: “I have known Otis for over 20 years. He doesn’t come off as being ignorant or stupid, but when it comes to prostate-cancer screening, he must not be as intelligent as he seems.” Or Skip Lockwood, the head of Zero, a prostate-cancer patient advocacy group, charge that Brawley is more concerned about saving men’s sex lives than about saving the men themselves.
David Walter Banks/Luceo
Dr. Otis Brawley has been an outspoken skeptic of routine P.S.A. testing.

Brawley has become the target of these attacks because of his blunt and very public skepticism about the routine use of the prostate-specific antigen, or P.S.A., test to screen men for early prostate cancer. “I’m not against prostate-cancer screening,” Brawley says. “I’m against lying to men. I’m against exaggerating the evidence to get men to get screened. We should tell people what we know, what we don’t know and what we simply believe.”

The P.S.A. test, which was approved by the U.S. Food and Drug Administration in 1986, has become an annual ritual for millions of middle-aged men who assume that finding prostate cancer early will prevent death. By 2008, nearly half of men over 50 reported that they were screened in the previous 12 months. Despite the seeming logic of the P.S.A. test, the evidence that it saves lives is far from conclusive, and Brawley is not the only one questioning it. A growing cadre of doctors, epidemiologists, patients and cancer biologists are rethinking its value. And the most recent studies, while not ending the debate, indicate that routine P.S.A. testing appears not to reduce the number of deaths, and if it does, the benefit is exceedingly modest.

Patients and their doctors are now faced with radically polarized views about the logic of routine testing. On one side are physicians like Mohler, who argue that the test can reduce a man’s chances of dying of prostate cancer, plain and simple. This side of the debate is passionate, backed by the persuasive conviction of men who have survived prostate cancer and well financed by the multibillion-dollar industry that has grown up around the testing and treatment of the disease.

The other camp makes a less emotionally satisfying argument: on balance, scientific studies do not support the claim that screening healthy men saves lives. Screening, Brawley and others argue, can lead healthy men into a cascade of further testing and treatments that end up injuring or even killing them. As Richard Ablin, who discovered a prostate-specific antigen, put it in an Op-Ed in The New York Times, using the P.S.A. test to screen for cancer has been “a public health disaster.”

So what should a man do when his doctor suggests a routine P.S.A. test? The U.S. Preventive Services Task Force, a panel of independent experts that evaluates the latest scientific evidence on preventive tests and treatments, is charged with making recommendations in just such situations. It already recommends against routine screening for men over 75. According to an internal document, in 2009 the task force conducted an in-depth analysis of data and seemed poised to give routine P.S.A. testing a “D” rating — “D” as in don’t do it — for any man of any age. But this was around the time that the task force stated that routine mammography for women ages 40 to 50 was not necessary for every woman.

That recommendation caused a public uproar, and Ned Calonge, the task-force chairman at the time, sent the P.S.A. recommendation back for review. One year later, in November 2010, just before midterm elections, the task force was again set to review its recommendation when Calonge canceled the meeting. He says that word leaked out that if the November meeting was held, it could jeopardize the task force’s financing. Kenneth Lin, the researcher who led the review, quit his job in protest, and now, nearly two years after its initial finding, it remains uncertain when the task force will release its rating for P.S.A. screening.

Cancer screening is a growing field; existing tests are becoming more sensitive, and new tests are constantly developed. We now have CT scanning for lung cancer, and there is also a blood test marketed by Johnson & Johnson known as a “liquid biopsy,” which searches for stray cancer cells in the bloodstream. More testing inevitably brings more treatment, because the urge to correct every cellular anomaly, no matter how small or potentially harmless, is practically irresistible. But if there is one lesson from the P.S.A. test, it is that more information and intervention do not always lead to less suffering.
 
The popularity of the P.S.A. test as the main weapon against prostate cancer is due in large measure to the earnest and passionate advocacy of William Catalona, a urologist from Northwestern University Feinberg School of Medicine. During his residency training at Johns Hopkins Hospital in the mid-1970s, Catalona set up a clinic for late-stage prostate-cancer patients. Back then, the only tool for finding prostate cancer was a digital rectal exam — actually feeling the prostate through the rectal wall. By the time many tumors could be detected, the cancer was already advanced, and removing the prostate surgically did not offer a reliable cure.

Catalona grew close to many of the men he treated, as well as to their families. “Prostate cancer is a terrible death,” he said. “They developed bone fractures, they had a lot of pain, they lost weight. They required heavy doses of narcotics.”

Catalona wanted to catch these cancers early, when they might be curable. He noticed that men with more advanced cancers at the time of surgery tended to have the highest P.S.A. levels. Could there be a bright line, a “safe” level of P.S.A. that could distinguish healthy men from those with prostate cancer? After reviewing his own patient records, he decided the cutoff level should be 4 nanograms of P.S.A. per milliliter of blood. He followed up with a study of 1,653 patients. The results, published in 1991 in The New England Journal of Medicine, showed that P.S.A. testing could detect prostate cancer several years earlier than a digital rectal exam.

The test quickly gained powerful support: Gerald Murphy, who held the position at the American Cancer Society now held by Brawley, pushed the society to endorse the test. In 1996, Gen. H. Norman Schwarzkopf, a prostate-cancer survivor, appeared on the cover of Time magazine over the statement “There’s a simple blood test everyone should know about.”

By then, doctors were using the test for routine screening. “P.S.A. testing was so easy,” says H. Gilbert Welch, a professor of medicine at the Dartmouth Institute (full disclosure: one author of this article is an instructor at Dartmouth). Doctors were predisposed to use the test for several reasons. First and foremost, there was the perception that early detection could save lives. It was also easy to administer. “It was a blood test,” Welch says. “You didn’t need equipment. . . . You didn’t need to put any scopes up any part of the body. Heck, you didn’t even need to ask the patient if he wanted it; you could just check off the box on a list of tests, like cholesterol, when you did a blood draw.” Today it’s common for doctors to order the P.S.A. test and patients to take it without talking about what it might really mean.

At one time, Otis Brawley, too, assumed that routine screening was the best medical practice. Sitting in his living room in an Atlanta suburb, Brawley recounted his transformation from believer to skeptic.

In 1988, after medical school at the University of Chicago, Brawley landed a prestigious fellowship at the National Cancer Institute in Bethesda, Md. There he came under the tutelage of Barnett Kramer, an oncologist and epidemiologist who went on to become the associate director of the institute’s early detection and community oncology program. Kramer walked Brawley through a short history of screening, beginning with the Pap smear, which has been an unqualified success, significantly cutting cervical-cancer deaths.

But other cancer screening tests had not worked out so well. For example, researchers at the Mayo Lung Project conducted a study between 1971 and 1983 to determine whether frequent chest X-rays could help reduce deaths from lung cancer. Chest X-rays detected lots of suspicious spots and shadows on the lungs and probably led to some cures of early lung cancers, but the study ultimately found no difference in death rates between the patients who were screened and those who were not.

Kramer suggested one probable explanation: diagnosing the spots picked up by X-ray often requires surgery, which carries a small but definite risk. Brawley knew that many spots seen on X-rays are simply old scars or minor abnormalities commonly seen in healthy people. With so many innocent blips detected, complications from lung biopsies and other invasive tests, along with treatment complications, could kill enough patients to negate any benefit from early detection.

Prostate cancer is the second-leading cause of cancer death among men, after lung cancer. In 2009, it was diagnosed in approximately 192,000 men. A small number of tumors are very aggressive, but the majority of prostate tumors are not likely to cause death. They grow very slowly, and only a fraction break out of the prostate, seed new tumors in other parts of the body and kill the patient. The current thinking is that about 30 percent of men in their 40s have prostate cancer, 40 percent of men in their 50s and so on, right up to 70 percent of men in their 80s. Yet only 3 percent of all men die from the disease. In other words, far more men die with prostate cancer than from it, and only a tiny fraction of prostate cancers ever cause symptoms, much less death.

But here is the tricky part: Unless there are symptoms or a finding on a physical exam, doctors generally cannot accurately predict which cancers are destined to be indolent, to sit around for years growing slowly, if at all, and those that will ultimately prove lethal.

In his discussions with Kramer, Brawley saw that these two pieces of information — the fact that a certain number of prostate cancers will never cause harm, and that doctors can’t reliably predict which cancers will be dangerous — had powerful and potentially devastating consequences for men. The first implication was that using the P.S.A. test to screen men who had no symptoms would uncover a huge reservoir of indolent cancers. Most of those cancers that men previously died with — and not from — would now theoretically be detectable. And once detected, the majority of those cancers would be treated.

The most frequent treatment then, as it is now, was the surgical removal of the entire prostate gland. The prostate sits at the base of the penis, wrapped around the urethra, which is the tube that carries urine and semen out of the penis. Trying to separate gland from urethra is a difficult job, and even the best of surgeons can damage the urethra or the bundle of nerves that initiate erections. About half of men who undergo radiation or surgery will have permanent side effects like impotence and incontinence. Up to 1 in 200 men die within 30 days from complications related to the surgery.

“You didn’t have to be brilliant to see that history was repeating itself,” Brawley says. “Doctors were just substituting a blood test for chest X-rays.”

Tim Glynn, a self-described country lawyer from Setauket, N.Y., was 47 in 1997 when he went to his primary-care doctor, troubled by a vague feeling of being down. After his physical exam, Glynn was sent to have his blood drawn. Along with thyroid and cholesterol levels, the doctor ordered a P.S.A. test. A week later, Glynn returned to hear the results. His P.S.A. was elevated. He was told to get a biopsy as soon as possible.
After the biopsy, he walked into a bar in the middle of the afternoon and ordered a martini. A few weeks later, Glynn’s urologist told him the biopsy showed prostate cancer and recommended that he have his prostate removed immediately. Glynn chose to do some homework first.

One of Glynn’s clients happened to be Richard Ablin, the scientist. Ablin told him that not all prostate cancers are alike, and that he could wait; if he developed symptoms, or if his P.S.A. shot up, he could always opt to be treated at that time. (Some doctors recommend “active surveillance,” in which the patient is periodically given P.S.A. testing and biopsies, rather than immediate treatment.) Glynn chose to hold off on surgery.

Kerri Glynn, Tim’s wife of now 39 years, was terrified by her husband’s decision. “I felt as if an ax had fallen,” she says. In her mind it was better to be safe than sorry, and safe meant being treated immediately. “She was a wreck,” Glynn says. “She was scared witless.”

His colleagues were also worried about his decision to forgo treatment. “My business partner was clearly very anxious, and my assistant asked if she should look for a new job,” Glynn recalls. “And there was the fear that if this became public knowledge, there would be clients who wouldn’t want to deal with us because they wouldn’t want to engage a lawyer who was going to be dead the next day. When you see the people around you falling apart, you sort of have to get treated for them, so you can go back to a normal life.”

For many people, not being treated after a diagnosis of cancer is psychologically unbearable. Our view of cancer, says Barnett Kramer, is still shaped by the fact that until relatively recently, cancers were only discovered when they were causing symptoms. Before current treatments were available, such cancers were often fatal. We can now screen for cancers long before they become symptomatic, but it’s still very difficult to imagine that they can safely be left untreated. Brawley says, “I have had patients say, ‘Damn it, I’m an American — you can’t tell me I have cancer and we’re going to watch — you have to treat it.’ ”

Glynn had the surgery. Fourteen years later, he still takes drugs for impotence. It would be more than a year following surgery before he had the energy to play a set of tennis again. “The toll that this took on energy and physicality was like being aged five years,” he says.

One way to look at Glynn’s story is as a success. His cancer was removed. His impotence is being managed. But Glynn sees it differently, and so do many other men who have been treated for prostate cancer. Darryl Mitteldorf is the executive director of Malecare, a cancer-patient support group. He says it is not uncommon for men to regret their decision to be tested and treated for prostate cancer. “We have men come in very upset, week after week, telling us what they’re not telling their doctors,” he says. One-third of men who are given a P.S.A. test were never asked if they wanted it. Of men who are asked, more than half say their doctor failed to mention possible side effects that result from treatment.
Brawley tells the story of a patient who had surgery and then underwent radiation, which left him with severe damage to both his rectum and ureter. “He had every side effect known to man,” Brawley says. “He had a bag for urine, a bag for stool, he was a terrible mess, in and out of the hospital with infections.” The man died six years after his surgery, from an overwhelming infection. Yet cancer statistics would list such a man as a success story, Brawley says, “because he survived past the five-year mark.” Would an untreated prostate cancer have killed him within six years, too? There is simply no way to know. 
Many doctors suggest that African-American men and those with a family history should be tested as early as age 40, because they are at increased risk of dying of prostate cancer. But Brawley, who is African-American and has declined P.S.A. screening himself, says this recommendation is based on conjecture, and even for men at higher risk, the test may cause more harm than good. Until the proper studies are done, he asserts, “We just don’t know.” 
The dueling narratives of P.S.A. testing boil down to the way each side frames the potential for harm from the disease compared with the collateral damage from the test and subsequent treatment. Mohler says, “P.S.A., when used intelligently to detect prostate cancer early in men after proper education . . . performs pretty well; it actually performs better than a mammogram.” P.S.A. advocates are concerned that statistics play down the value of each life saved. Some also argue that the statistics will validate their view as men are followed beyond 14 years. More important, they worry that if men reject screening, malignant cancers will go undiagnosed. 
David Newman, a director of clinical research at Mount Sinai School of Medicine in Manhattan, looks at it differently and offers a metaphor to illustrate the conundrum posed by P.S.A. screening. 
“Imagine you are one of 100 men in a room,” he says. “Seventeen of you will be diagnosed with prostate cancer, and three are destined to die from it. But nobody knows which ones.” Now imagine there is a man wearing a white coat on the other side of the door. In his hand are 17 pills, one of which will save the life of one of the men with prostate cancer. “You’d probably want to invite him into the room to deliver the pill, wouldn’t you?” Newman says. 
Statistics for the effects of P.S.A. testing are often represented this way — only in terms of possible benefit. But Newman says that to completely convey the P.S.A. screening story, you have to extend the metaphor. After handing out the pills, the man in the white coat randomly shoots one of the 17 men dead. Then he shoots 10 more in the groin, leaving them impotent or incontinent. 
Newman pauses. “Now would you open that door?” He argues that the only way to measure any screening test or treatment accurately is to examine overall mortality. That means researchers must look not just at the number of deaths from the disease but also at the number of deaths caused by treatment.
Many experts agree with Newman, and two large studies of P.S.A. screening, published in The New England Journal of Medicine in 2009, came to the same conclusion: There was no difference between the screened and unscreened groups in overall deaths. One trial, conducted in the United States, showed no reduction in prostate-cancer deaths over a period of up to 10 years when men 55 and older were screened. The other, which was carried out in several European countries, showed that screening reduced mortality from prostate cancer by 20 percent, yet the overall number of deaths in each group was the same. Newman gives one possible reason for this: the benefit of early diagnosis could be offset by complications from diagnostic tests and subsequent treatment.
Each study has been criticized for design and execution issues that might have skewed the results, but the failure to reduce overall mortality reported in the European study is probably no fluke, Newman says. An analysis of six studies of screening involving nearly 400,000 men, published last year in the British medical journal BMJ, found no significant difference in overall mortality when screened men were compared with controls. Philipp Dahm, a professor of urology at the University of Florida College of Medicine and lead investigator for the analysis, says the study shows that P.S.A. screening “does not have a clinically important impact” on overall mortality. Or as Kramer, an author of the U.S. study, crisply puts it, “Men may be trading one cause of death for another.” 
For Brawley, the greatest tragedy of P.S.A. screening is that it has been a distraction from making greater progress in reducing deaths with the one clear helpful thing: distinguishing between the prostate tumors that really need to come out and those that are better left alone. Instead, new types of P.S.A. screening are being promoted. “We live in a time when our failure to define questions properly has delayed our progress and harmed health,” he says. “We keep pursuing son of, son of P.S.A.”
As it stands, each man must decide for himself how he wants to play the odds. “Let’s put this in perspective,” says Welch, whose most recent book is “Overdiagnosed: Making People Sick in the Pursuit of Health.” “The European trial says 50 men have to be treated for a cancer that was never going to bother them to reduce one death. Fifty men. That’s huge. To me, prostate screening feels like an incredibly bad deal.” 
Other men, Welch acknowledges, may arrive at a different conclusion, and he is careful to avoid pushing his own patients in one direction or the other. The answer is ultimately personal, he says, and while studies of groups of people can feel unhelpful if you could be the one in the group with cancer, that is all we have to go on. 

The solution, in Welch’s view, and in that of a growing number of physicians, including Brawley, is to make sure men fully grasp the downstream decisions they may face as a result of screening — the risk of knowing too much. Studies have found that when men are given balanced information about both the cons and pros of P.S.A. testing, they are less likely to opt for screening than men who were merely offered the test. Given this, Brawley asks, how can it be ethical for a doctor not to inform men of the risks — or to fail to even tell a man that the test has been ordered? “If a man understands the risks and benefits and does not want to be screened, that decision should be supported,” he says. “But just saying that gets you in trouble.”

Shannon Brownlee (brownlee@newamerica.net) is acting director of the New America Foundation Health Policy Program and an instructor at Dartmouth Institute for Health Policy and Clinical Practice.
Jeanne Lenzer (jeanne.lenzer@gmail.com) is a freelance journalist and a frequent contributor to the British medical journal BMJ.
Editor: Vera Titunik (v.titunik-MagGroup@nytimes.com)

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