General Commentary to the “Management of Biochemical Recurrence after Primary Localized Therapy for Prostate Cancer” by Darwish O. M. and Raj G. V.

General commentary to the " Management of biochemical recurrence after primary localized therapy for prostate cancer " TO THE EDITOR: In a recently published review on management of patients with biochemical failure (BF) following primary definitive therapy for localized prostate cancer (PCa), Darwish and Raj (2012) stated that following radical prostatectomy (RP) patients who are at high risk for recurrence after radiation therapy (RT), based upon a salvage nomogram, should be spared from this treatment modality justifying it by a range of toxicities it causes. Additionally, in the algorithm for management of BF after primary therapy they suggested that patients with a short prostate-specific antigen (PSA) doubling time (PSA-DT) and PSA > 10 ng/mL should not be offered salvage RT at all. Do these recommendations provide the optimal use of salvage RT following RP? Unfortunately, we feel that they do not. While we agree with the authors that patients with higher PSA at the time of radiation (RT), short PSA-DT, high Gleason score, and other " bad " prognostic characteristics do generally worse than patients without those features, it does not mean that salvage therapy should categorically not be discussed and potentially offered to patients at high risk of recurrence. As a matter of fact, in the study that was cited in the manuscript (Stephenson et al., 2007), select patients with some " bad " prognostic features did remarkably well after salvage RT. The 6-year progression-free estimate in patients with PSA-DT ≤ 10 months and GS 8–10 with low PSA was 41%. When looking at PSA-DT, in particular those with the shortest doubling time may be at the greatest risk for PCa-specific mortality (PCSM). Therefore, although salvage RT may be less likely to prevent recurrence in this group in the ones who are salvaged with RT the benefit may be profound. This is supported by the analysis from Trock et al. (2008) who found, in a retrospective analysis of 635 patients with BF after RP, that there was an increase in PCa-specific survival after salvage RT in patients with short PSA-DT ≤ 6 months only and not in those with a longer PSA-DT. Ina similar retrospective analysis of 432 patients with BF after RP, the beneficial effect of salvage RT on all-cause survival was more prominent in patients with PSA-DT ≤ 6 months than in patients with PSA-DT > 6 months, with adjusted hazard ratios of 0.35 (95% CI 0.17–0.72, …