Prostate Cancer Staging and Grading

What does "staging" mean in reference to prostate cancer?

The "stage" of prostate cancer is defined as the estimation of the size and location of the cancer at the current time. More specifically, it references how extensive the cancer is within the prostate and if it has spread to tissues around the prostate or to other parts of the body. The stage of the cancer is the most important deciding factor in which treatment will be used.

How is the "stage" determined?

The usual initial staging studies include the ultrasound and pathology reports from the initial biopsy, the rectal examination, and often a bone scan. On occasion, a CAT scan (computerized axial tomography) or MRI (magnetic resonance imaging) will be done of the pelvic and abdominal areas, in addition to a chest X-ray.

What is the difference between "clinical stage" and "pathological stage"?

The terms "clinical stage" and "pathologic stage" are both used when referring to the stage of prostate cancer. The clinical stage is the stage estimated by the physician before any surgery is done. The pathologic stage is the true extent of the cancer as found by the pathologist in the prostate specimen after removal of the prostate and lymph nodes. One obvious dilemma is the fact that clinical stage and pathological stage do not always agree. That is, the cancer can be more or less extensive than estimated by the pre-operative examinations and tests. If no surgery is done on the prostate or lymph nodes, the clinical stage is the only stage that is obtained.

What are the stages called?

Two commonly used staging systems exist: ABCD and TNM. The ABCD is older and provides a broader description of the cancer than TNM. The TNM system describes the prostate (T), the lymph nodes (N), and evidence of metastatic disease (distant spread) (M) separately.

ABCD - With ABCD, the cancer is denoted by one letter followed by one number; for example, A1, B2, and so on.

TNM - With the TNM, the prostate is described by the "T," the lymph nodes by the "N" and distant spread by the "M." Each letter is followed by a describing number; for example, T2N0M0.

Stage A Prostate cancer at this stage cannot be felt and has no symptoms. The cancer is only in the prostate and is unsuspected. This stage of cancer is found when surgery is done for other reasons, such as for BPH (benign prostatic hyperplasia). All of these cancers are N0M0, meaning no extension of cancer or positive lymph nodes are suspected.
Stage A1 or T1a This cancer is not suspected by the urologist but can be found by the pathologist on prostate tissue removed for what was thought to be benign prostate enlargement. These cancers involve less than 5 percent of the prostate tissue removed (commonly referred to as "focal"). Usually, the cancer cells found are low-grade (discussed below).
Stage A2 or T1b This cancer is not suspected by the urologist but can be found by the pathologist on prostate tissue removed for what was thought to be benign prostate enlargement. These cancers involve more than 5 percent of the prostate tissue removed. The cancer cells found are either low or high grade (discussed below).
Stage B The cancer is limited to the prostate alone. That is, the cancer has not extended, grown or spread outside the prostate. All these cancers are N0M0, meaning no extension of cancer or positive lymph nodes are suspected.
Stage B0 or T1c Tumor is not felt on rectal examination. Biopsy is done only because of elevated PSA.
Stage B1 or T2a The cancer can be felt on rectal examination but involves only one side of the prostate and is less than 1.5 cm (3/5 of one inch) in size.
Stage B1 or T2b The cancer involves more than half of one lobe, but not both lobes of prostate.
Stage B2 or T2c The cancer involves both sides of the prostate.
Stage C or T3/4 Cancer cells have spread outside the covering (capsule) of the prostate to tissues around the prostate. The other glands that produce semen (seminal vesicles) may have cancer in them. All of these cancers are N0M0, meaning no extension of cancer or positive lymph nodes are suspected.
Stage C1 or T3a Cancer extends beyond prostate capsule on one side only.
Stage C1 or T3b Cancer extends beyond prostate capsule on both sides.
Stage C2 or T3c Cancer extends into one or both seminal vesicles (gland nearby prostate).
Stage C2 or T4a Cancer extends into bladder or rectum or sphincter (muscles that give urinary control).
Stage C2 or T4b Cancer extends into other pelvic structures, such as the muscles of the pelvic floor.
Stage C Cancers A denotes extension beyond capsule (C1/T3a if on one side, C1/T3b if on both sides)
B denotes bladder neck involvement (C2 or T4a)
C denotes seminal vesicle involvement (C2 or T3c)
D denotes sphincter involvement (C2 or T4a)
Stage D or N greater than 0 or M greater than 0 Cancer cells have spread (metastasized) to lymph nodes or to organs and tissues far away from the prostate. N0 mean no lymph node spread or metastases. M0 means no spread to other areas of body away from the prostate.
Stage D1 or N1 Spread to a single pelvic lymph node, less than 2 cm (4/5 of inch) in greatest dimension.
Stage D1 or N2 Spread to a single pelvic lymph node, more than 2 cm (4/5 of inch) but less than 5 cm (two inches) in greatest dimension, or to multiple lymph nodes all less than 5 cm.
Stage D1 or N3 Spread to any pelvic lymph node, greater than 5 cm (two inches) in greatest dimension.
Stage D2 or M1 Cancer cells have spread to lymph nodes far from the prostate or to any other parts of the body outside the pelvic region, such as the bone, liver or lungs.

Recurrent cancer

Recurrent disease means that the cancer has come back (recurred) after it has been treated. It may come back in the prostate or in another part of the body.

Are there any other methods for determining staging?

PSA (prostate specific antigen) has gained widespread use in the detection and monitoring of prostate cancer. Although PSA levels can be suggestive of tumor volume and stage, specific values for determining stage does not exist. Guidelines that are often followed suggest that most prostate cancers are confined to the prostate if the PSA is less than 10 ug/ml, particularly if the Gleason grade is less than 7. PSA values greater than 20 are associated with an increased risk of high stage disease. Transrectal ultrasound and computerized axial tomography (CAT scan) is generally thought to be insufficiently accurate for pre-treatment staging of prostate cancer. Magnetic resonance imaging (MRI) of the prostate gland has shown increased staging accuracy since the introduction of a special probe called the "endorectal coil." Its use is still considered investigational and is not used extensively at this point. Its accuracy (or sensitivity) is in the range of 70-75 percent. MRI of the spine, however, is widely accepted as a tool to confirm the presence of cancer in bones that are suspicious on bone scan.

What does "grading" mean in reference to prostate cancer?

The "grade" is defined by the pathologist from the prostate biopsy. The grade gives us an idea of how fast the cancer might be growing or how aggressive it might be. High-grade cancers grow faster and spread earlier than low-grade cancers.

How is the "grade" determined?

Today, cancer specialists usually use the Gleason grading system, named after a pathologist, Dr. Gleason, from the University of Minnesota. Dr. Gleason's system involves looking for different patterns of aggressiveness within the prostate and then giving two scores of 1 to 5. These two scores are added to give the total Gleason score, which will range from 2 to 10. The higher the score, the more aggressive the tumor will be. For example, a typical Gleason graded cancer might be written as Gleason 4+3 = 7, or Gleason 2+2 = 4. Rarely, only one score will be used in some medical reports and this can be confusing. To get the true total Gleason score in these instances, the number needs to be doubled.

The older system of grading used only three different grades: well differentiated, moderately differentiated, and poorly differentiated. It is still used in general discussions about cancer. Well-differentiated meant the cancer had more resemblance to normal prostate tissue and therefore usually did not grow or spread quickly. Poorly differentiated tumors did not resemble normal prostate tissue and usually grew quickly and spread to other tissues earlier. Moderately differentiated were in the middle.

To compare systems we say that:

  • Gleason 2, 3, and 4 are well differentiated
  • Gleason 5, 6, and 7 are moderately differentiated
  • Gleason 8, 9 and 10 are poorly differentiated.

Grade, while important, has less bearing on the treatment decisions than the stage. After the grade and stage are known, other factors also come into play before making any decision about future treatment.

Are there any other methods for determining "grade"?

Another less commonly used grading test looks at the number of chromosomes in the cancer cells or "ploidy" (ploy-dee). The test is called "flow cytometry." Normal human cells have 46 chromosomes. This is referred to as "diploid" (dip-ployed), meaning 23 pairs. When flow cytometry is used to count the chromosomes, we discover that some cancers have an extra chromosome and are called "aneuploid" (an-u-ployed). Anueploid cancers tend to spread more quickly and have a worse prognosis -- but not always. Other tests looking at chromosome abnormalities are being studied in research laboratories around the world.

While "ploidy" and other chromosome tests do give us some information, the stage of one's cancer is still more important in determining treatment options. Just as important, however, are each individual's health, life expectancy and current medical condition.