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Harvard Commentaries
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Reviewed by the Faculty of Harvard Medical School


Determining the Severity of Prostate Cancer


September 23, 2014

Prostate Cancer
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Features
Determining the Severity of Prostate Cancer
Determining the Severity of Prostate Cancer
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Doctors use three pieces of information to decide when a prostate biopsy is needed to confirm a diagnosis of prostate cancer.
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2011-09-03

Reviewed by the Faculty of Harvard Medical School

Determining the Severity of Prostate Cancer

Doctors use three pieces of information to decide when a prostate biopsy is needed to confirm a diagnosis of prostate cancer:

  • The results of a digital rectal exam (DRE)
  • A blood PSA (prostate-specific antigen) level
  • The results of a transrectal ultrasound (TRUS)

PSA is a protein produced by the prostate. Men with cancerous prostates tend to have higher blood PSA levels than men with healthy prostates. But since all prostate cells, noncancerous (benign) and cancerous (malignant), produce PSA, the test produces many false-positive and false-negative results.

When a biopsy is needed, most often the recommended procedure is a transrectal core biopsy.

Ways To Detect Prostate Cancer

To evaluate prostate cancer, doctors consider three factors:

  • The anatomic stage of the disease
  • The microscopic grade
  • The biologic evidence of its likely behavior

Anatomic Stage
Prostate cancer usually begins in one area of the gland and then spreads. It usually first spreads within the prostate, often very slowly. Those cancers that are destined to grow more quickly will next move toward the outside surface of the prostate (called the capsule). Next, it may spread further -- to the seminal vesicles and neighboring tissues. Finally, the prostate cancer may reach the lymph nodes and bones. The disease requires different treatment based on its location.

The major anatomic system for evaluating prostate cancer is called the TNM system. It is based on the size of the tumor and whether it has remained confined to one place or spread to lymph nodes and/or distant sites.

T represents the size and amount of local spread of the primary tumor. Very small cancers are called T1. Stages T3 and T4 are large cancers that have extended beyond the outer capsule of the prostate.

N represents the number and extent of spread to lymph nodes. N0 indicates no lymph node involvement. N1 through N4 correlate with the extent of the spread to the lymph nodes.

M is an indication of whether the cancer has spread to distant places (called metastases), such as the bones or lungs. M0 means no metastases. M1 means the cancer has spread to distant places.

Anatomic staging is crucial to planning treatment. The prognosis for men with prostate tumors confined to the prostate gland (stages T1 and T2) is better than in men with more advanced cancers. Men with early, organ-confined disease also have the option of surgery as a potential cure. Men with more extensive disease cannot be cured by surgery alone. They will usually need hormonal therapy, perhaps combined with radiation therapy.

Microscopic Grade
A prostate biopsy establishes the diagnosis of cancer. The biopsy also provides valuable information.

When a urologist performs a transrectal biopsy, at least 6 -- and often 12 to 20 -- tissue specimens are obtained. Pathologists examine each specimen (they call them cores). The fewer cores that have cancer cells, the better the outlook. In general, when at least two cores are positive and one of them contains at least 50% cancer cells, there is an increased risk that the tumor has spread to the outer surface of the gland (the capsule) and beyond.

Pathologists diagnose cancer by examining biopsy specimens under a microscope. But they also evaluate how malignant the cells look:

  • Well-differentiated cells look the closest to normal
  • Poorly differentiated cells have a wilder, more malignant appearance
  • Moderately differentiated cells lie between the extremes

In general, specimens with well-differentiated cancers have the best prognosis and poorly differentiated ones have the worst.

Prostate cancers also are classified using the Gleason grading system. The Gleason system combines two features of how prostate cancer appears under the microscope and grades each from 1 to 5 (5 is the worst):

  • Are the cells well or poorly differentiated or somewhere in between? Well differentiated cells get a 1. Very poorly differentiated cells get a 5.
  • Do groups of cancer cells still have a structure that is reasonably close to normal or are the cancer cells in balls that have obliterated the normal structure of the prostate gland? Close to normal gets a 1. Sheets of cancer cells with no normal structure get a 5.

Each feature is given a score. The lowest possible score is 2, which indicates a cancer that would likely be very slow growing and not need any treatment. The highest score is 10. This indicates a very aggressive cancer with a poor prognosis if not treated.

Scientists are working hard to develop better systems, but until they succeed, the Gleason score will remain the best guide to a tumor’s likely behavior.

Biological behavior
Anatomic staging and microscopic grading are valuable ways to predict how prostate cancer will behave, but they are imperfect. 

The blood PSA level helps predict how a man’s prostate cancer will behave. In general:

  • Men with PSAs below 10 ng/mL have the best outlook
  • Men with levels between 10 and 20 ng/mL have an intermediate prognosis
  • Men with PSAs above 20 are at high risk

The rate at which PSA levels rise over time is called the PSA velocity. A PSA rise of more than 2 nanograms per milliliter the year before a cancer was diagnosed also suggests that the prostate cancer is more aggressive.

Newer biologic markers are being studied. The most promising rely on identifying the genetic abnormalities that fuel the growth of malignant cells. These tests are still experimental.

 

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