A Breakthrough Study in Prostate Cancer

BY MARK SCHOLZ, MD

Ten years ago everyone agreed that surgery was the “Gold Standard” to which every other kind of treatment should be compared.  Now as we approach 2013, you rarely encounter the Gold Standard argument to bolster surgery as the preferred treatment approach.  What has led to the change in perspective and why has it taken so long for this change to come about?

Good Science Finally Leads to a Clear Answer

The primary cause for the changed perspective about surgery is the result of a well-performed scientific study published this year by Dr. Timothy Wilt in the New England Journal of Medicine.  The study has been a long time coming.  It was first conceived way back in the early 1990s when Dr. Wilt and others designed a definitive trial to test whether or not radical prostate surgery improves survival compared to observation. Even back then, researchers knew that prostate cancer can often behave benignly and were questioning the benefits of radical surgery.  Therefore, between 1994 and 2002 over five-thousand men were invited to participate in a study comparing immediate surgery with no treatment.  To make the comparison totally fair, individuals volunteering for the study had to be willing to have either surgery or observation based on the flip of a coin.  Most of the more than five thousand men who were invited to participate in the study refused. Ultimately, however, 731 men agreed to participate.

Modest Benefits for “Bad” Cancer, No Benefit for “Good” Cancer

At the start of the study the average age of the men participating was 67 and the median PSA was 7.8. After ten years the difference in prostate cancer mortality was essentially the same in both groups, i.e., within the expected range of statistical variation: 5.8% died in the surgery group and 8.4% died in the observation group.  However, subgroup analysis of the 251 men in the study who started off with PSA levels above 10 showed a modest improvement in survival for the men undergoing surgery: 5.5% died in the surgery group and 12.8% died in the observation group.

Validation of the Right Way to Look at Prostate Cancer

This picture of how different types of prostate cancer behave over long periods of time (having a high PSA for example versus having a low PSA) has been slowly forming in the minds of the prostate cancer experts over the years.  Dr. Anthony V. D’Amico, MD, PhD, Professor of Radiation Oncology at Harvard Medical School, is credited with developing the modern staging system that divides men into Low, Intermediate and High-Risk categories (At the PCRI we call them Shades of Blue, i.e., Sky, Teal and Azure).  Dr. Wilt’s study conclusively validates the fact that favorable prostate cancer—termed Low-Risk—can be safely monitored without immediate treatment, whereas men with High-Risk disease derive a modest benefit from immediate treatment.  His study also reported an intermediate outcome for the men with Intermediate-Risk disease: After 10 years, men in the Intermediate category showed no improvement in cancer survival with surgery.  However, there was a 10% lower incidence of metastases in the men with Intermediate-Risk who had surgery.   

Conclusion

Dr. Wilt’s study is an important breakthrough because it is the first modern, large, long-term, prospective, randomized study comparing treatment versus no treatment in men with relatively early-stage disease, i.e. diagnosed via PSA screening.  This study provides critically important scientific confirmation validating the policy of withholding radical treatment in men with Low-Risk disease.  The study also validates the predictive accuracy of the D’Amico staging system which functions by dividing men into Low, Intermediate and High-Risk categories.  Lastly, Dr. Wilt’s study provides a quantifiable measure of the degree of benefit associated with immediate surgery in men with Intermediate-Risk and High-Risk disease.  Using this information, individuals with High-Risk disease can better understand the rather modest survival advantages of surgery, and weigh them against the probable deleterious side effects, enabling them to determine for themselves whether or not they want to proceed with radical treatment.