Making Sense of the TNM Staging System

BY RALPH BLUM

In my last Blog I described the Gleason grading system, which urologists use to establish the aggressiveness of your cancer based on the pathologist’s analysis of your biopsy. If you are requesting copies of all your medical records (as you should) you may come across a tumor  staging code called the Tumor Node Metastasis (TNM) staging system.  This code is used to describe to doctors information about whether your prostate cancer is localized, regional, or advanced.

The letter “T” in the TNM system refers to the tumor.  Your doctor “stages” the tumor based on how big the tumor nodule feels when he does a digital rectal examination.  For example, information about size, on whether it is in one or both sides of the prostate, and on whether it has gone outside the prostate is communicated by the four categories—T1, T2, T3, and T4.

Subtypes of T1 (T1, T1a, T1b, T1c) or T2 (T2, T2a, T2b, T2c) refer to localized cancer, meaning the cancer has not spread beyond the prostate. Any of the T3 subtypes (T3a, T3b) refer to regional cancer, which means that the cancer extends just outside the prostate and may have gone into the seminal vesicles. T4 has only one category, and refers to cancer that has spread to the bladder and/or to other adjacent areas of the pelvis.

The “N” in the TNM code refers to whether the cancer has spread to the lymph nodes in the pelvis. N0 means it has not spread to the pelvic nodes; N1 indicates that it has spread. If the cancer has spread to the pelvic nodes, it is more likely to move beyond the nodes and into other parts of the body, making it harder to treat.

The “M” in the TNM staging system refers to whether the tumor has spread or metastasized beyond the lymph nodes in the pelvis. M0 means zero metastasis. M1a means the cancer has spread into the lymph nodes beyond the pelvic area. M1b refers to cancer that has spread to the bones. M1c means the cancer has spread beyond the lymph nodes and bones to other parts of the body.

At the initial staging of the cancer, your urologist first performs a digital rectal examination to determine the presence and status of the tumor. If he determines that the cancer is at a very low level perhaps he will not order further tests. But if he suspects that the cancer may have spread outside the prostate gland, he will order a CT scan, an MRI, or bone scan. Cautious or conservative doctors are likely to order all three of these imaging tests regardless of their findings in the DRE. So don’t assume that you may have advanced cancer just because your doctor sends you for a CT scan or MRI.

I realize that all this information is somewhat confusing (It begins to sound like loony runaway variations on the British Secret Service MI5, MI6, SIS and Lord knows what else). However, the fact remains that, by grouping your PSA level, Gleason grade, and TNM stage, your urologist can determine your prostate cancer’s risk level and advise you on your best treatment options.

Bottom line, the more you know the better.  Yours is really the decision that counts so you have to understand what is going on.  You can obtain more information about staging on the PCRI's blue community website at www.pcribc.org.

Whew, It’s Over!

BY MARK SCHOLZ

I just passed my annual stress test—the Prostate Cancer Research Institute (PCRI) conference. Lots of work, but certainly worth it--we had over 700 attendees from 41 states and 9 countries.  I was proud of all the 20 speakers, and particularly grateful for the contribution of Mark Moyad, MD who did a stellar job moderating.  Dr. Moyad and I reviewed some of the conference highlights on Sunday morning. They include reports on the following:

1. PET scans improve prostate imaging according to Dr. Dusing from Kansas City University and Dr. Kwon from the Mayo Clinic.

2. National Comprehensive Cancer Network (NCCN) guidelines recommend Active Surveillance for Low-Risk prostate cancer according to Dr. Klotz from the University of Toronto.

3. Multiple new chemotherapy combinations and agents—Carboplatin, Avastin, Xeloda, Custersin and Jevtana—are active against advanced prostate cancer according to Dr. Scholz.

4. Ipilimumab, an new immune treatment from Bristol Myers Squibb can induce dramatic remissions in advanced prostate cancer according to Dr. Kwon from Mayo Clinic.

5. A variety of very promising new agents—MDV-3100, TAK-700, XL-184—are in late stage trials.  Provenge, another new agent that works by stimulating the immune system is already FDA approved according to Charles Drake from Johns Hopkins.

The PCRI also announced at the conference, the launch of the Prostate Cancer Blue Community (PCBC); a web based prostate cancer community that is overseen by the PCRI helpline.  The PCBC has discussion forums about the conference and the different types of prostate cancer that we have broken down into Shades of Blue so that men can connect with other men in their same category of prostate cancer. The PCBC can be accessed at www.pcribc.org.

“Who’s On First?” Making Sense of the Gleason Score

BY RALPH BLUM

When you are diagnosed with prostate cancer, you need to understand the grading system that your doctor will use to recommend specific treatments. The grade indicates how aggressive the prostate cancer is, based on the pathologist’s evaluation of cancer cells taken during a biopsy. While all cancer cells look abnormal to a pathologist, low-grade cancers have cells that often look similar to healthy prostate cells. The more aggressive the cancer, the less the cells look like normal prostate cells.

Invented in 1966 by Dr. Donald Gleason, the Gleason grading system is relied on by pathologists worldwide to determine how severe your prostate cancer is. Here’s how it works:

The Gleason system assigns a grade to each of the two largest areas of cancer in the tissue samples from the biopsy. The lowest number on the Gleason grade scale is 1, and the highest is 5. The pathologist examines the biopsied tissue samples to determine where the cancer is the most prominent (the “primary grade”), and where it is next most prominent (the “secondary grade”). Then he assigns one score to the primary grade and one score to the secondary grade. The final Gleason score is the sum of these two grades. So a total score can range from a 2 (1+1) to a 10 (5+5), depending on how distorted the cancer cells look. Obviously, the lower the Gleason score, the better.

Total scores from 2 to 4 are very low on the cancer aggressive scale and, therefore, indicate that the cancer is slow growing and considered low-risk. Total scores from 5 to 6 are mildly aggressive but the cancer is still considered low-risk. A total score of 7 indicates that the cancer is moderately aggressive and considered intermediate-risk. And total scores from 8 to 10 are considered highly aggressive and the cancer is categorized as high-risk.

Hopefully you are still with me, because here comes the tricky part: In order to get clarity on your Gleason score, you need to get a breakdown of the two numbers that make up the total score—the primary grade first, then the secondary grade. The reason for this is that even when total scores are the same, not all Gleason scores are equal.  For instance, if your Gleason is 3+4=7 and your friend’s is 4+3=7, you are actually in slightly better shape than your friend. Here’s why: When the primary grade is 3, it means that the cancer cells have not deteriorated as far as the cancer cells with a primary grade of 4.

One other caveat: It is often advisable to get a second opinion on your biopsy slides, because not all pathologists are equal either. A pathologist at a world-class reference center, such as Stanford, the Mayo Clinic, or Johns Hopkins, should preferably give the second opinion, and most insurance programs will cover the cost.

Together with your PSA and tumor “staging” (more about this in my next blog), the Gleason Score is your doctor’s best shot at determining your prostate cancer’s risk factor and, therefore, your best indicator of appropriate treatment options.

Playing “Chicken:” Sometimes You Both Lose

BY MARK SCHOLZ

I have never seen a real game of chicken where two cars race head on toward each other to see who will swerve first, i.e., who is chicken. However, we are seeing an actual game of chicken being played out before our eyes on the national stage.

In one car in this are the pharmaceutical companies that are charging mind-boggling prices for their new cancer drugs. FDA approval of a new medicine is like hitting the lottery because the insurance companies are legally obligated to pay for the drug. Recouping the cost of developing a new drug is certainly justifiable. Even so, in my recent blog I cited the example of Zytiga (abiraterone), an effective new pill for prostate cancer that retails for $5,000.00 per month.

The other car in this game is the insurance companies, who, to control costs, have begun imposing artificial restrictions on coverage of Zytiga by insisting that chemotherapy be administered first, before Zytiga can be prescribed. By imposing this artificial restriction the insurance companies are getting involved in making decisions about treatment that historically have been left to the doctor. The insurance company’s rationale is that the studies of Zytiga that led to FDA approval were performed in men after chemotherapy, so in theory we don’t know if Zytiga will work before chemotherapy.  What a travesty!  Any cancer expert—for that matter, anyone with common sense—can tell you that starting treatment earlier works better than waiting until the disease is more advanced. 

I really don’t know how this scary game of chicken is going to end.  No insurance company has endless resources. Yet, thanks to effective research being performed by the pharmaceutical companies, many new (and expensive) drugs are coming on the market. Presently in my daily practice, people who meet the criteria—men who have had previous chemotherapy—and have adequate pharmaceutical insurance, are getting coverage for their Zytiga pills. Also, Johnson and Johnson, the manufacturer of Zytiga has a generous program for drug access for people who can’t afford the drug.  Even so, at some point the costs to society are going to become unsustainable. Just like the game of chicken, if both the parties wait too long to take corrective action, we can anticipate a crash.