The radiosensitivity index predicts benefit from HDR brachytherapy in high-risk prostate cancer

Abstract

Purpose or Objective There is a decline in the use of brachytherapy boost for high-risk prostate cancer patients despite an accumulation of clinical data supporting improved outcomes. HDR boost may be a convenient means of overcoming radioresistance that needs further investigation. A clinically validated multigene expression model of tumour radiosensitivity (RSI) was developed by Torres-Roca and colleagues and validated in multiple cohorts and disease types. In this study, the RSI gene signature was validated in two prostate cancer radiotherapy cohorts. Material and Methods A total of 386 D’Amico classified high-risk patients treated from 2008-2014 were identified for this analysis: 218 patients received intensity modulated radiotherapy (IMRT) to the prostate only (60 Gy in 20# or 74 Gy in 37# ) and 168 patients received IMRT (37.5 Gy in 15#) and a high dose rate (HDR) brachytherapy boost (15 Gy). This equates to a BEDα/β 1.5-3Gy of 120 – 180 Gy for IMRT only and 159 – 265 Gy for IMRT and HDR boost. Androgen deprivation was given to all patients with duration ranging from 3-36 months. Biochemical failure was defined as prostate-specific antigen (PSA) rise of ≥2 ng/ml above nadir post radiotherapy. The clinical end-point was progression-free survival (PFS). Gene expression data were generated from diagnostic needle core biopsies using Affymetrix Clariom S arrays. RSI scores were calculated using a published rankbased linear regression algorithm. The RSI score cut-off was the upper quartile to dichotomise patients into radioresistant (RSI-R) and radiosensitive (RSI-S). Kaplan- Meier statistics were used for survival outcomes. Results The mean follow-up for the entire cohort was 55 months (95% CI 56 – 61 months). The upper quartile cut-off for the RSI-R score was 0.41 (range 0.14 – 0.56). The 5-year PFS for radioresistant (RSI-R) vs radiosensitive (RSI-S) patients in the IMRT cohort was 54.9 % vs. 74.9% (p = 0.024). The 5- year PFS for RSI-R vs RSI-S in the HDR boost cohort was 76.2 % vs 71.4% (p = 0.71). Conclusion Our study validates for the first time use of the RSI in prostate cancer patients undergoing definitive (without surgery) radiotherapy. The RSI signature should be explored further to select patients with high-risk prostate cancer who should benefit from dose escalation with a HDR brachytherapy boost.