Every year more than 200,000 men in the United States are diagnosed with prostate cancer. In 2010 it is estimated that there were 217,000 new cases but only 32,000 cancer-related deaths. Since most men who get this disease are elderly, many die with, rather than of, the disease. Coincidental with improvements in screening (primarily the PSA blood test) and treatment the death rate is somewhat lower than it was twenty years ago.
However, for many if not most men, it may not matter whether their cancer gets diagnosed and treated when it is in a very early stage because it grows so slowly. Why then do most men who develop prostate cancer get aggressive treatment such as radical surgery or high-dose radiation if the death rate is so low? Until now the answer has been that we do not know who will die if untreated and who will live. All that is about to change.
In the past there have been prognostic markers which predicted prognosis. The PSA blood test can predict prognosis in newly diagnosed cases. A PSA over 20 at the time of diagnosis, or a rapidly rising test prior to the diagnosis, is a bad sign. The Gleason score, a measure of how angry looking the cancer is under the microscope, is also a predictor of bad outcome. However, neither a low PSA nor favorable Gleason score has been used to predict who did not need to be treated because they were not considered reliable enough for that purpose.
What is new, then? Since the sequencing of the human genome was completed several years ago researchers have been looking at cancers for clues as to how genetic mutations (acquired changes in the genetic makeup of the tumor) factor into the aggressiveness of cancer. This has been well worked out for breast cancer, where two commercially available tests on the tumor itself can predict who needs chemotherapy and how the patient is likely to do overall. Some progress has been made in this regard in colon cancer as well, and lesser degrees of progress have been made in several other cancers.
Only recently have several groups of investigators reported on breakthroughs in prostate cancer. Dr. DePinho and colleagues at Dana Farber Cancer Institute at Harvard have identified a metabolic pathway in prostate tumors that is controlled by a certain gene called SMAD4. This had led them to develop a gene test for prostate cancer that should be highly predictive of outcome in patients whose tumors are tested. At the moment this test has not been sufficiently validated for general use but investigators in this field believe that this scientific approach has huge potential. At almost the same time Dr. Cuzick and colleagues in London announced that they had identified several mutated genes in prostate cancer which would predict outcome. They have devised what they call the CCP (cell cycle progression) score, which, when combined with pre-treatment PSA accurately predicts outcome. This test is also not commercially available yet.
Why worry about this? The treatment for prostate cancer is quite morbid. Radical prostatectomy in the most experienced hands still results in a very high rate of post-operative impotence and a somewhat lower rate of urinary incontinence. Radiation therapy does not have quite the same complication rate but is not harmless either. If tens of thousands of men every year could be spared treatment the quality of their lives would improve and health care costs would fall.
Prostate cancer is unique among cancers in that many men so afflicted can live out their life expectancy free from symptoms without treatment. We are currently treating nearly everyone so that a subset of patients can live longer. When we can identify that subset ahead of time a large number of men will be spared this difficult treatment.