Radical prostatectomy viable for locally advanced prostate cancer, according to study

Washington-Radical prostatectomy is worthy of consideration in the management of locally advanced prostate cancer, report the authors of analyses of oncologic outcomes from men enrolled in a large, prospective, multicenter European database.

First author Steven Joniau, MD, a urologist at University Hospital Leuven, Belgium, presented the findings at the AUA annual meeting in Washington. Study data were based on 1,045 men operated on at one of seven high-volume centers between 1987 and 2009. The data were derived from a large, multicenter research project on high-risk prostate cancer (EMPaCT, European Multicenter Prostate cAncer Clinical and Translational research group), which Dr. Joniau leads with co-authors Martin Spahn, MD, Paolo Gontero, MD, and Alberto Briganti, MD.

Mean follow-up after prostatectomy was 71.3 months. The men had a mean preoperative PSA of 28.3 ng/mL, and almost 90% had cT3a disease. Biopsy Gleason score was 2-6 in 39% of men, but 8-10 in about one-fourth of the cohort.

High survival rates observed

Based on Kaplan-Meier estimates, median survival had not yet been reached at 15 years for clinical progression-free survival, cancer-specific survival (CSS), or overall survival (OS); 10-year survival rates for these endpoints were 85.4%, 88.6%, and 72.3%, respectively, and half of the men remained biochemical recurrence free at 10 years.

During a discussion of the paper, Dr. Joniau noted that additional data from the study reported at another AUA session showed patients with only one high-risk factor fared very well, with a 10-year CSS rate exceeding 95%.

"Results of several prospective trials establish the superiority of radiotherapy with neoadjuvant or adjuvant ADT versus RT alone for treating locally advanced prostate cancer," Dr. Joniau said. "However, evidence supporting surgery for these men is mainly derived from limited series of highly selected patients.

"Our data suggest RP can be a valuable alternative to combined RT and ADT for men with locally advanced disease. Interestingly, one-fifth of the men in our cohort were confirmed on pathology to have only localized disease, while more than one-third had specimen-confined disease with negative nodes and margins, and patients with those features did particularly well. However, about two-thirds of patients needed multimodal strategies. Now, further prospective trials should be undertaken to clarify the exact need and order of adjuvant strategies in surgically treated patients with clinical locally advanced prostate cancer."

Analyses were also conducted to identify predictors of poor oncologic outcomes after RP in this population of locally advanced prostate cancer patients treated surgically. In multivariate analysis, advanced pathologic stage was the strongest predictor of a negative CSS outcome. Hazard ratios (HRs) for pT3b and pT4 disease were 9.26 and 14.86, respectively. However, there were wide 95% confidence intervals for HRs, and only pT4, but not pT3b, had independent predictive value for OS with an HR of 2.02.

"As expected, pathological Gleason score 8-10, positive surgical margins, and lymph node invasion also independently predicted a poor outcome for both CSS and OS, while neoadjuvant ADT was a negative risk factor for CSS but not for OS," said Dr. Joniau, calling attention to the high negative impact of positive surgical margin on CSS and OS, since it is a surgeon-related variable.