Staging for Prostate Cancer. We will be discussing our old friend, the TNM staging system, T for tumor size, N for lymph node involvement, and M for presence of metastases. Remember, Prostate Cancer Is Staged Based on the TNM System and the Gleason Score, and these tests can help us when necessary. Bone scans to help us assess if prostate cancer has spread the bones. CT or CAT scans to help us assess if prostate cancer has spread the lymph nodes, and MRIs to help us assess if prostate cancer has broken through the prostate capsule. The whole purpose of cancer staging is to determine how advanced the cancer is, because that helps us predict disease course, or prognosis and treatment options. Cancer staging helps us evaluate the invasiveness of the cancer, the TNM system tells us about the characteristics of the tumor within the origin, or primary tumor in the prostate. Whether its in nearby lymph nodes, and whether it's in any distant tissues. The T stage for prostate cancer is special, because of the T1c designation. T1c refers to a small prostate cancer that is detected by PSA screening. It cannot be felt by a digital rectal exam. A T2 cancer can be felt by digital rectal exam, and it is confined to the prostate. A T3 cancer is invading through capsule. A T4 cancer is when that invading tumor is invading into the rectum, or bladder specifically. Node Status, cancer staging is first done based on clinical and imaging assessments. If a CT scan is not performed, we don't know the node status and the clinical stage is the Nx. If a CT scan is performed, and no lymph nodes are seen, the patient stage is clinical stage, and zero or no regional lymph nodes. If regional lymph nodes are seen on the CT scan, the patient is staged at clinical stage and one. I remind you that the CT scan does not tell us whether the lymph nodes are cancer or not, simply that they are enlarged. However, because they are enlarged on the CT scan, the patient is still staged as end one disease. The M for metastases staging, again, tells us whether cancer is detected on clinical imaging. Mx means it was not assessed, for example, a bone scan was not done. M1 says that we have found metastases, or evidence that suggests metastases somewhere. M1a refers to lymph nodes that are beyond the pelvis. M1b is disease in the bones, and M1c is disease in other sites, for example, the liver or lungs. That gives us the TNM system, but prostate cancer is also assessed by grade. To understand prostate grading, we have to understand what a pathologist sees when they look under the microscope. This is an example of normal prostate architecture at low power under the microscope. It consists of glands where PSA is secreted into, surrounded by areas of tissue that is referred to as trauma. A normal prostate consists of large glands that are lined with a layer that is two cells thick. Here is an example of prostatic inflammatory atrophy, or PIA. What you see is that the glands are still large, but they have started to involute a little bit, and there is associated inflammation in the stroma next to it. Prostatic Intraepithelial Neoplasia, or PIN, is considered a precursor lesion to cancer. On the left, you see a normal gland consisting of the lining of the gland that is two cell layers thick. In the example of PIN on the right, you can see multiple cell layers growing into the gland itself. The lining of the gland itself is still intact. So, you see normal stroma in both the picture in the left, and the picture in the right. The difference between NORMAL and PIN is that the gland is filling up with abnormal cells in the example of PIN. We will see that what happens with cancer is that the abnormal cells start to invade into the stromal layer, and the glands themselves change. Dr. Gleason was a famous pathologist who developed a scoring system for changes in the prostate, as it became more and more dedifferentiated. He designed the system that scored what he was looking at under the microscope from 1 to 5. Pattern one was small uniform glands that were well differentiated. Pattern two was more stroma between these small glands with the appearance of more disorganization. Pattern three demonstrated that these glands were starting to break down, and have infiltration into the struma. Pattern four demonstrated irregular masses of these glands, so that you started to lose the glandular formation. And Pattern five was simply sheets of anaplastic cells with very few glands at all. These describe the patterns to get the score we actually have to do more than that. The first thing that the pathologist does it look down at the slide that was taken in biopsy, or taken at the time of prostatectomy and look for the most dominant pattern of a tumor. This is assigned the primary grade, one through five. The pathologist then looks for the second most common pattern, and assigns a one through five grade again. The Gleason score then becomes the sum of the primary and secondary grade. For example, three plus four equals seven, or four plus three equals seven. If there is a small component of a third, and generally more aggressive pattern, the pathologists will assign a tertiary grade to the cancer. For example, they will call it three plus four with tertiary pattern five. Lets take a closer look at this. Here is a pathologic slide showing Gleason pattern 3 cancer. You see small glands, and the small glands have lost the two cell layers. There is always only one cell layer. This is an important diagnostic criteria for cancer. There is only one cell layer in each of the glands. Gleason pattern four demonstrates that these small glands have started to fuse. You can still see circular patterns, but you can see that they are smeared. The arrow points this out. Gleason pattern five demonstrates no gland architecture, you just see sheets of cells. The Gleason's score is associated with risk of recurrence for patients, and is an important part of prostate cancer staging and grading. Over the last five to ten years, pathologists have essentially only reported cancers as 3+3 or higher. This has led to confusion with patients, because their best score, which actually correlates with Gleason pattern six, is actually associated with very low risk of recurrence. But they say, doctor, why is my score six out of ten, why isn't it one out of ten? Doctor Epstein from John Hopkins and his colleagues from around the country had started to score prostate cancers on a scale of one to five, correlating with the Gleason patterns shown here, 3 + 3 = 1, 3 + 4 = 2, 4 + 3 = 3, 4 + 4 = 5 and higher scores equal to The Hopkins/Epstein system of 5. This scoring system will be used more and more in the coming years. Overall, staging for prostate cancer requires thinking about the TNM system, tumor nodes metastasis system, as well as the grade. Once you have the TNM system and the grade, you can assign a stage, stage 1, stage 2, stage 3 or stage 4. Unfortunately, classic tumor staging for prostate cancer has not kept up with the times. Here you see an example of a staging table that includes the TNM system, but also a grading system that's not even used anymore because we now use the Gleason grade. Modern staging requires understanding the size of the tumor, T1, T2, T3, T4, the nodes, as well as the metastatic profile of the patients. We will discuss the various treatments for prostate cancer. Based on stage and grade, as we talk about local and advance treatment. Patients often ask their position, what are the chances might cancer has spread based on what you know about my cancer? The Partin Tables use clinical features of prostate cancer, Gleason score, serum PSA and clinical stage to predict whether the tumor will be confined to the prostate. The tables are based on the accumulated experience of urologist's performing radical prostatectomy. At the Brady Urological Institute at Johns Hopkins, for decades, urologists around the world have relied on the tables for counseling patients pre-operatively and for surgical planning. For example, if the Partin Table suggests that the cancer has escaped the prostate, the patient and the physician may decide that surgery is not their best option. These tables are available for anyone's use at Urology.jhu.edu. Here are a couple examples of how the Partin tables work. If the patient has a PSA of zero to four, has a Gleason 6 tumor, and is clinical stage T1c, their chances of having an organ confined cancer at the time of surgery are 92%. The chances of that cancer having invaded into the seminal vesicles, a poor prognostic sign is 1%, and the chances having a lymph node involve is almost 0. This would suggest to a patient, that if he has his prostate out, he will be cured of his cancer, and that surgery is potentially a good idea. If a patient has a PSA that's higher at seven, a aggressive tumor, Gleason 8 and has a T2a lesion palpable on rectal exam, his chance of having an organ confined cancer are only 45%. There's a 39% chance that the cancer will have broken through the prostate, and an 11% chance that the seminal vesicle is involved. There's a 4% chance that surgeon would find cancer in a lymph node. These numbers do not suggest that surgery should not be done. However, they do suggest to a patient and a physician that the patient may need more therapy after surgery. For example, adjuvant radiation therapy, if it turns out that a seminal vesicle was involved, or a lymph node was involved at the time of surgery.
