What’s different in the genomes of radiorecurrent prostate cancer? In this study, targeted DNA and RNA sequencing was performed on 41 biopsy proven locally radiorecurrent prostate cancers (median 7 years after RT) and compared with treatment naive samples from The Cancer Genome Atlas and Decipher GRID. Recurrent tumors were enriched for mutations in DNA repair genes such as RAD51B and BRCA 1 and 2. A much larger proportion of recurrent tumors also had low androgen receptor activity (61% v 9%) and a significantly higher Decipher risk score (median 0.8 v 0.66). Not unexpectedly, a predominance of these recurrent tumors had a PAM50 basal subtype (56% v 20%), which is associated with low AR pathway activity, aggressive behavior, and genomic instability. This could argue for consideration of earlier, more aggressive salvage local therapy and/or biologically informed systemic therapy for radiorecurrent disease. | Neilsen, Int J Radiat Oncol Biol Phys 2025
