I agree with Drs. Forman and Velasco that the optimal management of patients with an elevated prostate-specific antigen (PSA) level after prostatectomy remains to be determined. The broader issue, however, is optimizing the management of post-prostatectomy patients who are at risk for recurrence. Hence, the dilemma: Should we wait for a chemically apparent recurrence before instituting treatment? Or, should we, on the basis of available information, quantify the risk of recurrence and the possible side effects of therapy and determine whether or not adjuvant radiotherapy is warranted based on the risk/benefit ratio?
The results of Southwest Oncology Group study 8794 (SWOG 8794) comparing observation vs postoperative radiotherapy, particularly with regard to survival differences, should help us resolve this dilemma. Until the results of this study are known, I believe that the best strategy is to individualize postoperative recommendations based on the anticipated risk/benefit ratios of the options of observation vs treatment.
Radical prostatectomy studies have shown that fewer than 60% of patients have disease confined to the prostate and that the incidence of positive margins ranges from 16% to 46%. Gleason grade, capsular and seminal vesicle involvement, and nerve invasion have all been found to predict the risk of recurrence. This risk can be as high as 68% in a patient with both high Gleason score and capsular penetration. These prognostic features support the need for adjuvant therapy.
Selecting the Best Option
The ability of adjuvant postoperative radiotherapy to prevent local recurrence is well documented. Postoperative radiation is widely recognized as an effective strategy, with temporary side effects and minimal toxicity, thus making it a compelling treatment for patients whose likelihood of recurrence ranges from 30% to 70%.[5,6]
At present, it is unclear whether delayed treatment has an adverse effect on outcome, but current nonrandomized studies have detected a difference in favor of the adjuvant postoperative approach. To be sure, this result should be confirmed by large, randomized studies that have sufficient power to detect such a difference.
Observation is a compelling option given the recognized ability of PSA to detect a recurrence and the effective treatment protocol of Drs. Forman and Velasco. I remain hesitant, however, to recommend observation as the only or best option. Careful assessment based on all available information, including age, potency, performance status, and the risks associated with therapy, should guide the practicing physician in the selection of the best alternative.