Comparison of genetic mutations in bladder cancers that arose following radiotherapy for prostate cancer with those in primary bladder cancers.

Radiotherapy (RT) for prostate cancer increases the risk of bladder cancer. The genomic landscape of bladder cancer following RT for prostate cancer and its differentiation from bladder cancers that develop without a history of pelvic RT remains unclear. We examined gene mutations in bladder cancers that developed following RT and those that developed without prior RT. Fourteen patients who developed primary bladder cancer following brachytherapy were categorized into radiation-associated bladder tumor (RA-BT) group, whereas 33 patients diagnosed with primary bladder cancer without a history of pelvic RT were classified into the bladder tumor (BT) group. The frequency of TERT promoter mutations was 35.7% and 63.6% in the RA-BT and BT groups, respectively (p = 0.112). Among the other characteristic mutations, FGFR3 and TP53 were frequently observed in both groups (FGFR3: RA-BT vs. BT, 14.3 vs. 42.4%; TP53: RA-BT vs. BT, 50 vs. 33.3%). Rare mutations in bladder cancer were more frequently observed in the RA-BT group, including ADGRB3 (28.6%), CBL (21.4%), TGM7 (21.4%), and BTK (14.3%). There were significantly more C → T substitutions in the RA-BT group than in the BT group. In our study, the genetic mutations in the RA-BT group had distinct features from those in the BT group.