Risk of Biochemical Failure in Patients With High-Risk Prostate Cancer Treated Definitively or Postoperatively With Intensity Modulated Radiation Therapy

Abstract

Current treatments for high risk prostate cancer include surgery and definitive radiation. Many patients treated with prostatectomy require adjuvant radiation for high risk pathologic features, or salvage radiation after biochemical failure. No randomized trials comparing these modalities have been completed. Here we present outcomes of patients with high risk prostate cancer treated with definitive radiation or post-operative radiation in the adjuvant or salvage setting using intensity modulated radiation therapy (IMRT). One hundred eighty-one patients with National Comprehensive Cancer Network high risk prostate cancer treated with IMRT at our institution between 2006 and 2010 were included. One hundred fifty-four patients were treated definitively (prostate doses ranging 7020-7920 cGy, 180 cGy daily fractions), and 27 were treated post-operatively; 12 adjuvantly for high-risk pathologic features, and 15 as salvage treatment following biochemical failure (prostate bed doses 6480-6660 cGy). Pelvic lymph nodes were treated in 105 patients with high risk of lymph node involvement at diagnosis as determined by the Kattan Nomogram. Rates of concurrent or adjuvant androgen deprivation therapy (ADT) were 59% (definitive cohort) and 52% (post-operative cohort). Overall survival (OS) and freedom from biochemical failure (defined by 2 consecutive PSA rises to >1.5 ng/mL) were determined using Kaplan-Meier analysis, and hazard ratios were determined by Cox Proportional hazards model. The mean age at diagnosis was 59.8 years (post-operative), and 65.6 years (definitive cohort) (range, 46-85.4 years). With a median follow-up of 43 months (5.1 months-15.4 years), 3- and 5-year OS was 96% and 88% for the post-operative cohort, and 92% and 83% for the definitive cohort, respectively. Overall survival for the two groups was not statistically different. Patients treated with post-operative as opposed to definitive IMRT were significantly more likely to experience biochemical failure with a hazard ratio of 6.4 (p = 0.006). Biochemical failure was not different with ADT (p = 0.12). Many patients with preoperative high risk prostate cancer require adjuvant or salvage RT after surgery. In our cohort, patients with high risk prostate cancer treated with postoperative IMRT following prostatectomy had a statistically higher risk of biochemical failure compared to those treated with definitive IMRT. Possible referral bias of highest risk post-operative patients was not accounted for, but we plan to expand the analysis to include all high risk patients treated with up-front prostatectomy at our institution.