Clinical and genetic determinants of toxicity and quality-of-life (QOL) outcomes for SBRT in Asian prostate cancer.

Abstract

95 Background: There is limited data on clinical and patient-reported quality of life (PRO-QOL) outcomes after stereotactic body radiotherapy (SBRT) in Asian men with localised prostate cancer. Demographic differences with regard to PRO-QOL outcomes may be due to variation in germline genetics. We therefore conduct a single-institution prospective phase II trial of prostate SBRT in Asian men with intermediate-risk prostate cancers (IR-PCa). Additionally, we investigated association of dosimetric and genetic factors with outcomes. Methods: Patients with biopsy-proven NCCN-defined IR-PCa were recruited. SBRT was delivered at 36.25 Gy/5fr using a Linac-based RapidArc technique. Adverse events (AEs) were assessed with CTCAEv4.0 and IPSS; PRO-QOL assessed using the EPIC instrument at baseline, 1 and 2-year post-SBRT. Germline genetics were profiled by whole exome sequencing (30X). Results: 65 patients were recruited over the period of 2014-2016 (median follow-up = 30 mo). We observed 4 acute ≥G2 gastrointestinal (GI) events (3 fecal urgency, 1 diarrhea). Longitudinal assessment of acute genitourinary (GU) events by IPSS showed worsened symptoms that peaked at 1 wk post-SBRT (44.6% vs 6.2% at 1 mo for men reporting scale upgrade). There was no significant association between acute GU effects (by IPSS) and dosimetric parameters of the irradiated urethra and bladder. PRO-QOL scores demonstrated minimal change over time across all domains; however, sexual bother in the top 50th percentile subgroup at baseline indicated ≥20% worsening of scores for 10/32 (31%) at 12 mo and 5/12 (42%) at 24 mo; which was not associated with Dosemax to the penile bulb (P = 0.1). We observed a high frequency of germline mutations in DNA repair genes (N = 10; 15.4%), including two BRCA2 stop-gain and frameshift mutations. In particular, BRCA2 mutations were detected in 2 of 4 cases with ≥G2 GI effects, independent of rectal dose. Conclusions: While prostate SBRT is well tolerated in our Asian cohort, there appears to be demographic differences in sexual bother compared to Caucasian cohorts. Interestingly, we observed a higher than expected prevalence for germline mutations in DNA repair genes, which may predict treatment response. Clinical trial information: NCT02313298.