Think About Surgery for High-Risk Prostate Cancer, Concludes Study

Nick Mulcahy

October 01, 2010

October 1, 2010 — Radical prostatectomy should be a treatment option for men with high-risk prostate cancer, according to a study presented yesterday at the 84th Annual Meeting of the North Central Section of the American Urological Association, held in Chicago, Illinois.

In a retrospective analysis of the 1238 men who underwent surgery and the 344 treated with external-beam radiation plus hormone therapy, the cancer-specific survival rate was 92%.

Median follow-up for the men treated with surgery was 10.2 years, and for those treated with external-beam radiation plus hormone therapy was 6 years.

"Our results do not suggest that surgery is for all men with high-risk prostate cancer, but it should be discussed as a treatment option," said lead author Stephen Boorjian, MD, a urologist at the Mayo Clinic in Rochester, Minnesota.

"The optimal treatment for high-risk disease continues to be debated," added Dr. Boorjian. However, surgery has not been favored, even by urologists, he told Medscape Medical News.

"The bias for the nonsurgical treatment of high-risk prostate cancer is multidisciplinary," said Dr. Boorjian, adding that he is unaware of any "pathologic basis" for this "therapeutic nihilism."

Another prostate cancer expert interviewed by Medscape Medical News believes there is an optimal treatment for high-risk prostate cancer.

Mark Scholz, MD, a medical oncologist at the Prostate Cancer Research Institute in Los Angeles, California, advises men with high-risk disease to have "state-of-the-art [intensity-modulated radiation therapy] with at least 7800 rads, along with hormone blockade for at least 18 months."

"Men with high-risk disease who elect to undergo surgery all too often have positive margins and need radiation anyway. Why should the poor souls be subjected to both surgery and radiation?" he asked.

Hormone Therapy for the "Weak and Feeble"?

The new study was a collaboration by investigators from the Mayo Clinic and those from the Fox Chase Cancer Center in Philadelphia, Pennsylvania. The former provided data on surgery patients and the latter provided data on radiation patients.

High-risk disease was defined according to National Comprehensive Cancer Network criteria: a prostate-specific antigen (PSA) score of 20 or higher, a biopsy Gleason score of 8 to 10, and a clinical stage of T3 or greater.

Of the 1847 patients with aggressive prostate cancer involved in the study from 1988 to 2004, 1238 underwent surgery and 609 were treated with radiation therapy. Of the 609 receiving external-beam radiation therapy, 344 also received androgen-deprivation therapy (for an average of 22.8 months).

Researchers analyzed their cancer-specific and overall survival rates. Although the cancer-specific survival rate was equal for the 2 groups of patients, the overall survival rates were not.

The overall survival rate was 77% for surgery, and was significantly better (P < .001) than radiation plus hormone therapy (67%) or radiation alone (52%).

In a press statement, Dr. Boorjian discussed the overall survival differences and the role of hormone therapy.

"Patients with radiation and hormone therapy were 50% more likely to die than patients who had surgery," he said. "This was true even after controlling for patient age, comorbidities, and features of the tumors. These results suggest that the use of hormone therapy in patients who received radiation therapy may have had adverse health consequences."

But when asked if hormone therapy adversely affected overall survival, Dr. Scholz, who was not involved in this study, objected strenuously.

"No. Absolutely not!," he said. "The difference is due to subjective differences between the 2 groups. Uncontrolled-for factors are always operative in the retrospective selection of men for surgery vs radiation. Healthier, stronger men get surgery, while weaker, more feeble men get radiation. This is always seen in these retrospective comparisons."

Dr. Scholz defended the use of hormone therapy in general for prostate cancer.

"There is no convincing evidence that hormone blockade shortens life or causes excess heart attacks if weight gain is attended to and blood sugar levels are kept in check," he said. "Hormone blockade extends life in randomized trials, both disease-specific and overall survival. The only studies that show shorter survival are retrospective comparisons in large insurance databases that can't control for the selection biases of physicians who reserve hormone blockade for the 'weak and feeble'," he explained.

Dr. Boorjian admitted that further study is needed to determine if hormone therapy was a factor in the differences seen in overall survival.

Notable Study

Dr. Boorjian also emphasized a number of strengths of the study.

First, compared with past studies that have looked at surgery and radiation, it has a large number of patients, and they are exclusively high-risk patients. Previous studies that have compared the 2 modalities have been for "all comers," with low numbers of high-risk patients, observed Dr. Boorjian. Also, there is longer-term follow-up in this study than in past efforts.

Funding for the study was provided by the National Cancer Institute. The authors have disclosed no relevant financial relationships.

84th Annual Meeting of the North Central Section of the American Urological Association. Abstract 19. Presented September 30, 2010

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