Long-term results of post-prostatectomy radiotherapy: A large institutional experience

INTRODUCTION AND OBJECTIVES: Randomized trials and consensus statements support the consideration of adjuvant radiation therapy (RT) following prostatectomy for adverse pathologic features (pT3 or positive margins) although its use remains low. Whether early salvage RT is as effective as immediate adjuvant therapy remains unknown. METHODS: A retrospective single institutional analysis of 728 post-prostatectomy patients receiving RT between 1993 and 2012 was performed. Early salvage RT was defined as radiation received for a biochemical recurrence with postoperative PSA ≤ 0.5ng/ml. A Cox regression multivariable analysis (MVA) was used to identify clinical and treatment-related risk factors associated with biochemical recurrencefree survival, freedom from salvage androgen deprivation therapy (ADT), distant metastasis (DM), and overall survival (OS). RESULTS: 187 patients were treated with adjuvant RT for adverse pathologic features, while 541 patients received salvage RT (184 of whom received early salvage and had initial pT3 disease and/or positive margins). Median follow-up from surgery was 7.0 and 8.9 years in the adjuvant and salvage cohorts, respectively. Median time from surgery to adjuvant RT was 4.5 months, and median time to first detectable PSA in the salvage cohort was 1.98 years (Range 0.014-15.4 years). In MVA, higher Gleason score, pT-stage, seminal vesicle involvement, and shorter interval between surgery and first detectable PSA were associated with increased risk of biochemical failure, DM, and subsequent need for ADT. Younger age (P<0.0001), lower pre-op PSA (p=0.005), and longer interval between surgery and first detectable PSA (P=0.007) were associated with increased OS. When compared to early salvage, adjuvant RT was associated with significantly improved 10-year freedom from biochemical failure (73.9% vs 59.5%, HR 0.60 (95%CI: 0.4-0.9), P=0.01); however there were no statistically significant differences in terms of 10-yr freedom from ADT (91.2% vs 83.2%, HR 0.67 (95%CI: 0.36-1.2), P=0.2), DM (95.8% vs 91.8%, HR 0.86 (95%CI: 0.3-2.2), P=0.8), and OS (97.8% vs 95.2%, HR 1.7 (95%CI: 0.6-4.6), P=0.3). CONCLUSIONS: Postoperative RT confers excellent long-term disease control, a finding validated by the long follow-up in this series. Adjuvant RT is associated with reduced risk of PSA recurrence though not DM, OS, or need for subsequent ADT when compared to early salvage. Rational optimal timing of postoperative RT awaits report of the results of large ongoing randomized trials.