Grading and Staging Prostate Cancer

A cancer's grade describes how closely its cells resemble the normal cells of the area in which it began. When prostate cancer is described as low grade, its cells look quite a bit like other prostate cells. They are said to be highly differentiated, which simply means that they retain many of the qualities that make prostate cells different from other cells in the body. Intermediate grade prostate cancers are more abnormal looking than low grade prostate cancers. These cells are said to be moderately differentiated, so, although a pathologist can still recognize them as prostate cells, they appear disorganized and unusual. A high grade prostate cancer cell is poorly differentiated and barely looks like a prostate cancer cell at all. The grade of a particular man's prostate cancer is an important consideration when deciding upon treatment options because we have discovered that high grade cancers are more likely to grow quickly and to spread than low grade cancers. There are two main methods of grading cancer: the general one described above and the Gleason grading system.

The staging of prostate cancer is also highly significant in determining the best options for treatment. A cancer's stage is determined by considering three factors: the size of the tumour, whether the cancer has invaded lymph nodes close to the prostate, and whether there are any distant metastases. There are two main staging systems. The most common is the detailed TMN staging system. Less used is the Whitmore-Jewett staging system.

In both staging and grading, the higher the numbers the worse the news.

THE GLEASON GRADING SYSTEM
This system is named after pathologist Donald Gleason. He graded prostate cancers on a scale of 1 to 5. Grade 1 cancers are the closest to normal cells, and grade 5 cancers are the strangest looking. Grade 3 is the kind of cellular pattern most often found in men diagnosed with prostate cancer.

Grade 1: Cells resemble normal prostate tissue, and they are well differentiated. The tiny glands of the prostate are round, have defined edges, and are packed tightly. The tumour is not expected to grow quickly.

Grade 2: Cells are less normal looking and less well differentiated. The glands are still round but are loosely packed with less distinct edges.

Grade 3: The cells are moderately differentiated. The glands are larger with irregular shapes and spacing. Their edges are badly defined and show infiltration.

Grade 4: The cells are poorly differentiated. Glands are of different sizes and shapes, and they are fused together in masses or chains.

Grade 5: The cells are very strange looking and poorly differentiated. Glands are not really discernable, and the tissue appears composed of solid cellular sheets, single cells, or nests of tumour.

Gleason Score
Because one man often has a number of different grades of cancer evident within his biopsy samples, Gleason develop a scoring system. To determine a prostate patient's Gleason score, a pathologist first decides which two grades of cancer are most evident in that patient's biopsied tissue. These grades are added together to reach his Gleason score, which will be a number between 2 and 10. For example, if cells that follow the grade 3 pattern are most common, but about 10 per cent of the cells follow the grade 1 pattern, a man would have a Gleason score of 4 (dominant pattern 3 + secondary pattern 1 = 4). If the secondary pattern makes up less than 5 per cent of the cancer, it is considered insignificant, so the grade of the dominant (and really only significant) pattern would be added to itself (dominant pattern 3 + dominant pattern 3 = 6).

A Gleason score of 2 to 6 is usually considered low, which means that the cancer cells may be similar to normal prostate cells and have a tendency to grow slowly.

A Gleason score of 7 (3 + 4 or 4 + 3) is considered intermediate-in between in its strangeness and speed of growth.

A Gleason score of 8 to 10 is called high. Usually the cells are very different from prostate cells and grow quickly.

A word of caution: Even low Gleason scores of 5 or 6 may be composed of a Gleason grade 4 or 5 pattern of cells (e.g., 2 + 4 = 6). Research shows that the presence of these poorly differentiated cancer cells (Gleason grade 4 or grade 5) is dangerous. So even low Gleason scores can be worrisome, and a Gleason score of 6 that is composed of mostly poorly differentiated cells (4 + 2) is riskier than the same score composed of moderately differentiated cells (3 + 3).

TNM STAGING
This staging system gives information concerning the cancer's size and extent. How big is the tumour? How far has the cancer spread? The T represents the primary tumour. The N represents the nodes of the lymphatic system (lymph nodes). And the M represents metastasis (or whether there is evidence of the cancer's spread to distant areas).

T Stage TX The primary tumour cannot be assessed. T0 There is no evidence of a primary tumour. T1 The tumour cannot be felt during a digital rectal exam or seen during a transrectal ultrasound. T1a The tumour is found incidentally when physicians are checking for some other problem. It is present in less than 5 % of the tissue removed. T1b The tumour is found incidentally when physicians are checking for some other problem. It is present in greater than 5 % of the tissue removed. T1c The tumour is identified during a biopsy (e.g., performed to investigate a higher than normal PSA level.)

T2 The tumour can be felt during a digital rectal exam or seen during a transrectal ultrasound. It is confined within the prostate. T2a The tumour takes up less than half (less than 50 %) of one lobe of the prostate. T2b The tumour occupies one half (50 %) or more of one lobe of the prostate. T2c The tumour is in both lobes of the prostate. (See the diagram below.)

T2c: The tumour involves both lobes.

T3 The tumour can be felt during a digital rectal exam as it is greater than 6 cm. It extends beyond the prostate's outer skin or capsule. T3a The tumour extends beyond the prostate capsule either on one side (unilaterally) or on both sides (bilaterally) of the prostate. T3b The tumour has invaded the seminal vesicles.

T4 The tumour has invaded or is attached to tissues next to the prostate other than the seminal vesicles. T4a The tumour has spread to the neck of the bladder, to the external sphincter (the muscles that help control urination), or to the rectum. T4b The tumour has spread to the floor or the wall of the pelvis.

N Stage This element of staging refers to whether the cancer has spread to any lymph nodes and to the size of any cancer in the lymph nodes. STAGE T4 WITH CANCER IN REGIONAL LYMPH NODES NX The regional lymph nodes cannot be assessed. NO Cancer has not spread to any lymph nodes. N1 Cancer has spread to one or more of the regional lymph nodes. Sometimes, you might see the designation N2 or N3. Both mean that there is cancer in the regional lymph nodes. N2 is used to indicate that the cancer is larger than 2 centimetres but smaller than 5; N3 is used to indicate that the cancer is larger than 5 centimetres.

M Stage This staging designation gives information about metastases. M0 means that there are no distant metastases; the cancer has not spread beyond the regional lymph nodes. M1 Means that there are distant metastases; the cancer extends beyond the regional lymph nodes (to lymph nodes outside the pelvis) or to the bone or distant organs, e.g., the lungs, liver, or brain. M1a The cancer has spread to non-regional lymph nodes. M1b The cancer has spread to the bone. M1c The cancer has spread to other distant sites. WHITMORE - JEWETT STAGING SYSTEM In the Whitmore-Jewett staging system, which is sometimes called the Jewett staging system, prostate cancer is classified first by letter (A through D), and then by number.

Stage A - The cancer is at an early stage, it is not detectable by digital rectal exam, and there are no clinical symptoms; cancer cells are confined to the prostate gland.

• A1 Cancer cells look very much like normal cells (well differentiated or slightly abnormal), and they are focused in one area.
• A2 Cancer cells are more abnormal (moderately or poorly differentiated), and cancer is in several locations within the prostate.

Stage B - The cancer is confined to the prostate capsule, but it is detectable either by digital rectal exam or by an elevated PSA reading.

• B0 Cancer cells are confined to the prostate and cannot be detected by digital rectal exam; the cancer causes an elevated PSA level.
• B1 There is one area (nodule) of cancer in one lobe of the prostate.
• B2 There is extensive cancer in one lobe of the prostate, or the cancer is in both lobes of the prostate.

Stage C - The cancer has spread outside of the prostate capsule to the area near the prostate gland. Cancer may be in the seminal vesicles, but it has not spread to the lymph nodes or to more distant parts of the body.

• C1 The cancer extends beyond the prostate capsule.
• C2 The cancer extends beyond the prostate capsule and obstructs the bladder or urethra.

Stage D - Refers to metastatic prostate cancer. The cancer has spread to regional lymph nodes or to distant bones, organs, or tissues.

• D1 The cancer has spread only to regional lymph nodes.
• D2 The cancer has spread to distant lymph nodes, bones, organs, or tissues.
• D3 Refers to D2 prostate cancer patients who have relapsed after treatment.