Androgen receptor splice variant expression and prostate cancer recurrence after salvage therapy

Radiotherapy (RT) with or without androgen deprivation therapy (ADT) is standard salvage therapy for men with local or biochemical recurrence of prostate cancer after prostatectomy, but there is an unmet need for biomarkers to identify potential non-responders. We hypothesized that androgen receptor splice variants (ARVs) are detectable in primary prostate cancer and may modulate response to salvage RT+ADT. We identified a retrospective cohort of prostate cancer patients treated with prostatectomy followed by salvage RT + ADT, and we performed targeted RNA-seq of archival formalin-fixed paraffin-embedded prostatectomy samples to comprehensively characterize the landscape of ARVs. Overall design: We performed targeted RNA-seq using a custom library of >3000 primers spanning all AR exons and introns. 43 prostatectomy samples from the salvage RT+ADT patient cohort were sequenced. 6 additional prostatectomy specimens from a separate cohort of localized prostate cancer patients and 7 tumor samples from another cohort of metastatic prostate cancer patients were also sequenced using the same methodology.