INTRODUCTION

When a patient is found to have prostate cancer, his physician must learn many things about the patient and the cancer. Two important pieces of information about that individual's cancer are the STAGE and GRADE. No decisions about treatment can be made until this information is estimated.

STAGING PROSTATE CANCER

The STAGE is defined as the estimation of extent (size and location) of the cancer at the current time. More specifically, how extensive is the cancer within the prostate and if it has spread to tissues around the prostate, or to other parts of the body. The studies vary from patient to patient depending on various factors. The usual initial staging studies include the ultrasound report and pathology report 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, and a chest X-ray. The stage of the cancer is the most important deciding factor in which treatment will be used.

Clinical Stage versus Pathological Stage?

In some instances, physicians will discuss 'clinical stage' and 'pathologic stage'. 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 Staging systems are used?

Two commonly used staging systems exist--ABCD and TNM.

The ABCD is older and is a broad description of the cancer. The TNM system describes the prostate (T), the lymph nodes (N), and evidence of metastatic disease (distant spread) (M) separately.

With ABCD the cancer is denoted by one letter followed by one number A1, B2 etc.

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, T2aN0M0. This may be confusing but ask if you have questions.

--Stage A --

Prostate cancer at this stage cannot be felt and causes no symptoms. The cancer is only in the prostate and was 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 was not suspected by the Urologist but found by the pathologist on prostate tissue removed for what was thought to be benign prostate enlargement. These cancers involve less than 5% 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 was not suspected by the Urologist but found by the pathologist on prostate tissue removed for what was thought to be benign prostate enlargement. These cancers involve more than 5% of the prostate tissue removed. The cancer cells found are either low or high grade (discussed below).

The cancer is limited to the prostate alone. That is, the cancer has not extended or grown or spread outside the prostate. All of these cancers are N0M0 meaning no extension of cancer or positive lymph nodes are suspected.

--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.

A denotes extension beyond capsule (C1/T3a if on one side, C1/T3b if on both sides)

B denotes bladder neck involvment (C2 or T4a)

C denotes seminal vesicle involvment (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.

Another new staging system that is used by some to describe the various aspects of Stage D disease are as follows:

D0 Elevated Acid Phosphatase

D1 Positive pelvic lymph nodes

D1.5 Rising PSA after failed radiation or surgery

D2 Metastatic disease in bone and/or other organs (lung, liver, etc)

D3S Hormonal sensitive prostate cancer

D3I Hormonal insensitive prostate cancer

What is new in Staging?

The stage of one's cancer is one of the most important factors in determining how the cancer might be treated.

A new test to predict spread of cancer is called 'Microvessel Density' or Biostage. This test is done of the biopsy specimen and help predict whether the cancer has spread beyond the prostate.

Another research development that is not yet perfected involves looking for substances or cell parts of prostate cancer in the blood. In other words, we would suspect spread of prostate cancer out of the prostate if cell parts or proteins from the prostate cancer can be found in the blood. We are looking at many substances, but the most researched substance is called RT-PCR, which stands for 'reverse transcriptase - polymerase chain reaction'. Much more testing will be needed before these types of blood tests will determine treatment options.

Other experimental predictors of cancer stage involve looking at the gene, protein and DNA makeup of individual cancer cells. These include p53, bcl-2, OA 519, HER-2/neu, NM 23, p21, NSE, PC 1, E-cad, PD 41, PCNA, Ki67, Rb, bcc, and PSNA. Prostate specific membrane antigen (PSMA), apoptosis (programmed cell death), and neuroendocrine differentiation are also being studied. These are very technical terms and are not meant to confuse you. None of these tests are reliable enough to be used by your physicians as staging tools as of yet.

Other staging tools

PSA (prostate specific antigen) has gained widespread use in the detection and also the 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%. 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.

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GRADING 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. 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 - 5. These two scores are added up to give the total Gleason score which will range from 2 - 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. Some experts believe that if the cancer contains any Gleason 4 or 5 tumor, whatever the total score, the chances for spread outside the prostate are higher.

The older system of grading used only three different grades: well-differentiated, moderately differentiated, and poorly differentiated. It is still used in general discusions about cancer.

Well-differentiated meant the cancer had more resemblence 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.

Other tests to help GRADE prostate cancer

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 chormosome 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.