The co-authors of Invasion of the Prostate Snatchers, blog alternate posts weekly. We invite you to post your comments.

Tuesday, March 25, 2014

Shades of Blue, Trying to Simplify a Complex Situation


How can one disease be so vast?  Actually, it really isn’t one disease; there are hundreds of variations: Prostate cancer can be slow or fast growing, responsive or unresponsive to treatment, metastasizing early or not metastasizing at all.  In fact, selecting treatment for prostate cancer would be simpler if these extreme “either-or” types of examples I just cited were common. In reality, most men’s cases are not so extreme, they lie somewhere in the middle.  Selecting the best treatment, one that matches each variety of prostate cancer, is a really big challenge. Therefore, the process begins by trying to understand the disease as well as we can.

Characterizing the Disease
People often assume that differences in the way cancer behaves—life threatening vs. benign—comes from observing the same illness at different time points.  What’s often misunderstood is that distinct varieties of prostate cancer also exist. It’s not all one disease. This doesn’t mean that the stage of disease is unimportant. It’s just not the whole picture.  Patients frequently ask, “Am I stage A, B, C, or D?” without realizing the lettering system is just a description of what the surgeon feels during his finger exam. PSA and the Gleason grade are just as important as the stage of the disease. What can be confusing is that no single element comprehensively defines the disease. For example, one man with a higher PSA may do well while another man whose PSA is low may do poorly.

A Widely-Accepted Classification System
Therefore, a classification system to help predict cancer aggressiveness requires a “grid” that incorporates multiple prognostic elements—the letter-stage, PSA, Gleason and scan results.  Dr. Anthony D’Amico from Harvard is credited with developing the modern system that uses PSA, Gleason and stage to divide newly-diagnosed prostate cancer into low, intermediate and high-risk categories.

Building on the D’Amico system, and to further highlight the differences between categories, the Prostate Cancer Research Institute (PCRI) has named the risk categories with different Shades of Blue* and expanded the grid to include two more categories: men with disease relapsed after treatment with a rising PSA and men with metastatic disease or disease that has become resistant to hormonal therapy.

The Five Shades of Blue:  

Sky for low-risk
Teal for intermediate-risk
Azure for high-risk
Indigo for PSA-relapsed disease after treatment
Royal for men with metastases or hormone resistance

Does the system separate men into distinct categories?  Yes. For example, in a study published by Dr. Timothy Wilt in the New England Journal of Medicine, 731 men volunteered between 1994 and 2002 either to have immediate surgery or observation alone.  The subsequent outcome showed higher cancer mortality with in men in a higher-risk (Azure) category compared to Sky or Teal. It also showed an 8% improvement in ten-year survival rates for men in the Azure category when they underwent surgery (rather than observation).  Surgically-treated, intermediate-risk men (Teal) showed a 10% reduction in the incidence of metastases compared to the men who did not have surgery. Men in the low-risk category (Sky) showed no difference in mortality or metastases with or without treatment. Dr. Wilt’s study, therefore, went beyond merely validating the predictive ability of the D’Amico staging system. The study also provided a measure of the degree of benefit associated with doing surgery.

General Treatment Recommendations

While there are no absolute rules for treatment, as a starting point, here are some general guidelines:

Sky (low-risk): observation or monitoring with active surveillance

Teal (intermediate-risk): monotherapy, limiting treatment to a single therapy such as IMRT or surgery or brachytherapy

Azure (high-risk) combination therapy with IMRT, brachytherapy and hormone blockade

Indigo (relapsed-disease): Treatment intensity tailored to the location in the body of the relapsed disease and to the PSA doubling time rate

Royal (advanced-disease): Multimodality immunotherapy, hormonal therapy, chemotherapy and radiation sequentially or in combination

The message is that before treatment can be selected what we are treating needs to be accurately defined.  The starting point, therefore, is to begin with dividing prostate cancer into five broad categories or Shades of Blue.  By doing this, the number of treatment options can be narrowed down and finding the right treatment becomes easier.   

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