The Timing Of Salvage Postprostatectomy Radiation Therapy: Waiting For The Psa To Climb Above 0.2 May Compromise Outcome

Recent American Society for Radiation Oncology/American Urological Association guidelines state that the effectiveness of salvage postprostatectomy radiation therapy (SRT) is greatest when administered at lower levels of prostate-specific antigen (PSA) with a recommendation to start before PSA exceeds 1.0. However no guidelines are given as to what level this should be, and with ultrasensitive assays men are aware of a rising PSA at levels below 0.1. The aim of this study was to review the time to biochemical failure for prostate cancer patients receiving SRT based on index PSA (iPSA) level prior to initiating treatment. Patients referred to our institution for consideration of SRT for a rising PSA following surgery were accrued into a prospective database. Baseline demographic data and tumor and treatment factors were collected including patient age, pathologic T and N stage, margin status, Gleason score, LVSI, ECE, PSA nadir postsurgery, use of androgen deprivation therapy (ADT), months from surgery to SRT, and iPSA prior to commencement of SRT. Study endpoint was time to biochemical failure (defined as post RT nadir +0.2, commencing hormone therapy, or physician’s judgement of a biochemical failure). Analysis of time to biochemical failure was performed using the Kaplan Meier method. Multivariate analysis was performed using Cox Proportional Hazards Model. One hundred ninety-four patients received salvage intensity modulated radiation therapy to a mean dose of 69.7 Gy between January 2008 and December 2013 given in 34 fractions. At analysis, median follow-up was 32 months. For patients with an iPSA of <0.1 (n=34), ≥0.1 to <0.2 (n=63), and ≥0.2 (n=97), rates of biochemical failure at 5 years were 22.4%, 33.4%, and 49.7%, respectively. Compared to the iPSA <0.1 group, the hazard ratios for biochemical failure at 5 years for an iPSA ≥0.1 to <0.2 was 2.2 (95% CI 0.7-6.7, P=.16), and iPSA ≥0.2 was 3.9 (95% CI 1.4-10.9, P=.01). Factors predicting time to biochemical failure included Gleason score, LVSI, ECE, and iPSA. After adjusting for known prognostic factors on multivariate analysis, iPSA, use of ADT, and Gleason Score 8 to 10 were all significant (P=.01). The presence of a positive margin was borderline significant in the multivariate analysis with a hazard ratio of 0.5 (P=.052) compared with a negative margin. Increasing iPSA levels are associated with an increasing risk of biochemical failure even after adjusting for known prognostic factors. Waiting for a PSA to rise above 0.2 may significantly compromise biochemical control.