Ten year outcomes of moderately hypofractionated salvage post prostatectomy radiotherapy and external validation of a contemporary multivariable nomogram for biochemical failure

Abstract

PURPOSE: Although there is high level evidence supporting moderately hypofractionated radiotherapy for definitive prostate treatment, there is less evidence for its use in the post prostatectomy setting. We externally validated a contemporary nomogram predicting biochemical failure (BF) after salvage radiotherapy (SRT) and report long term disease control outcomes for hypofractionated SRT to the prostate bed.

METHODS AND MATERIALS: A retrospective review was performed for 112 patients treated with hypofractionated SRT (52.5Gy/20 fractions using 3D conformal radiotherapy) for pT2-4R0-1N0/XM0 prostate adenocarcinoma, with post-operative PSA greater than 0.1ng/mL or rising. Freedom from biochemical failure (FFBF), distant metastasis (DM), cancer specific mortality (CSM) and overall survival (OS) were analysed from commencement of radiotherapy. Cox regression was performed on FFBF to account for covariates. BF was defined as a PSA ?0.4 ng/mL and rising after SRT. Early SRT was defined as SRT commencing at a pre-SRT PSA of ?0.2 ng/mL.

RESULTS: Median follow up was 10.0 years (interquartile range 9.3-10.7 years), median pre-SRT PSA was 0.4 ng/mL and ADT was used in 14% of patients. Five/ten year FFBF, DM, CSM and OS was 68%/51%, 7%/16%, 5%/11%, and 90%/75%. FFBF for early SRT compared to late SRT was 81% vs 66% at five years and 68% vs 49% at ten years. On multivariable analysis, pre-SRT PSA, ISUP grade group, SVI, and ADT use were associated with FFBF. The nomogram c-index was 0.67, and it overestimated FFBF by 10/15% at five/ten years, with confidence intervals overlapping the line of unity.

CONCLUSION: Hypofractionated SRT provides long term disease control outcomes comparable to conventionally fractionated radiotherapy. Early SRT provides improved disease control, with two thirds of patients with pre-SRT PSA of ?0.2 ng/mL being free of BF at 10 years. We performed the first external validation of the Tendulkar salvage nomogram which showed a robust model performance.