Stereotactic Body Radiation Therapy for Locally Recurrent Prostatic Carcinoma after Prior Therapeutic Irradiation: Prostate-Specific Antigen Response, Disease-Free Survival, and Toxicity

Abstract

Salvage success with acceptable toxicity has been reported with high dose rate (HDR) brachytherapy in patients with locally recurrent adenocarcinoma of the prostate following prior radiation therapy (RT), though limitations include invasiveness and scarce availability in some regions. We prospectively evaluated PSA response, disease-free survival and toxicity using “HDR-like” prostate stereotactic body radiation therapy (SBRT) local salvage treatment. From 2/09 to 1/18, 50 patients with biopsy-proven local recurrent prostate cancer post-RT were enrolled in this IRB-approved trial and 47 treated. Pre-existing RT toxicity > grade 1 was an exclusion criteria. Median interval to SBRT salvage was 88 months post-RT (range 32-180) and 43/47 patients had prior “conventional fractionation only” RT, the remainder had brachytherapy, SBRT or post-radical prostatectomy plus prostate bed RT. Median recurrence Gleason score was 7 (34% ≥ 8). MRI-defined prostate volume plus any extraprostatic extension comprised the planning target volume (PTV). 34 Gy/5 fractions were given, delivering HDR-like intraprostatic dose escalation (Dmax ≥ 150% of prescribed). Concomitant androgen deprivation therapy (ADT), though not encouraged, was not specifically prohibited. 7/47 treated patients had ADT in addition to salvage SBRT. Toxicities were assessed using CTCAE v. 3.0. A total of 47 treated patients had a median 36-month follow-up (range, 0–96; 34 patients followed ≥ 1 year). Median pre-salvage SBRT baseline PSA of 3.7 ng/mL decreased to 0.1 ng/mL & <0.1 ng/mL by 2 and 5 years, respectively, excluding patients with relapse. Actuarial 2- and 5-year biochemical disease free survival (bDFS) measured 80% & 66%, respectively. Excluding the 7 patients treated with ADT resulted in a 2% decrease in 2-year bDFS, no change in the 5-year bDFS and no change in the 2- and 5-year median PSA result. RT toxicity > grade 1 was limited to the GU domain, with actuarial 19% grade 2+ and 9% grade 3+ rates by 5 years. Limiting the analysis to salvage of “conventional fractionation only” RT failures, grade 3+ GU toxicity incidence decreased to 3%. No acute or chronic GI toxicity > Grade 1 occurred. Post-SBRT salvage bDFS to 5 years is encouraging and appears comparable to published HDR brachytherapy results. The PSA response kinetic appears similar to that seen in de novo patients treated with SBRT; though with early biochemical relapse seen more commonly in this group (≤ 2 years out). Grade ≥ 3 SBRT-induced GU toxicity was rare in post “conventional fractionation only” SBRT salvage cases, appearing more frequently in the small subset treated after other prior RT situations (e.g. – post-brachytherapy). There was no serious GI toxicity in this series. SBRT salvage of post-radiotherapeutic local recurrence appears feasible, with larger patient numbers and longer median follow-up required to confirm this result. With IRB approval, the protocol has been expanded to a sample size n = 100 and the study continues.