High-dose salvage intensity-modulated radiotherapy with or without androgen deprivation after radical prostatectomy for rising or persisting prostate-specific antigen: 5-year results

Abstract

Background: Long-term results with salvage radiotherapy (SRT) for a biochemical recurrence after radical prostatectomy (RP) are poor. It has been suggested that radiotherapy doses >70 Gy might result in improved outcome.

Objective: To report on the late toxicity profile and outcome of patients treated with high-dose salvage intensity-modulated radiotherapy (HD-SIMRT) with or without androgen deprivation (AD).

Design, setting, and participants: Between 1999 and 2008, 136 patients were referred for HD-SIMRT with or without AD. The median follow-up was 5 yr. Indications for HD-SIMRT were persisting prostate-specific antigen (PSA) or a rising PSA following RP. All patients were irradiated at a single, tertiary, academic centre. AD was initiated on the basis of seminal vesicle invasion, preprostatectomy PSA >20 ng/ml, Gleason score ≥ 4+3 (n=43), or personal preference of the referring urologist (n=54).

Intervention: A median 76-Gy dose was prescribed to the RP bed using intensity-modulated radiotherapy (IMRT) in all patients. AD consisted of a luteinising hormone-releasing hormone analogue for 6 mo.

Measurements: Univariate and multivariate analyses were used to examine the influence of patient- and treatment-related factors on late toxicity, biochemical relapse-free survival (bRFS), and clinical relapse-free survival (cRFS).

Results and limitations: The 5-yr actuarial bRFS and cRFS were 56% and 86%, respectively. On multivariate analysis, the presence of perineural invasion at RP (hazard ratio [HR]: 6.19, p=0.001) and an increasing pre-SRT PSA (PSA 0.5 ng/ml: HR: 1; PSA 1-1.5 ng/ml: HR: 1.60, p=0.30; and PSA >1 ng/ml: HR: 2.70, p=0.02) were independent factors for a decreased bRFS. The addition of AD improved bRFS (HR: 0.33, p=0.005). On multivariate analysis, none of the variables was a predictor of cRFS. The 5-yr risk of grade 2-3 toxicity was 22% and 8% for genitourinary and gastrointestinal symptoms, respectively.

Conclusions: IMRT allows for safe dose escalation to 76Gy with good bRFS.