Genomic Features of Muscle-invasive Bladder Cancer Arising After Prostate Radiotherapy

Muscle-invasive bladder cancer (MIBC) is a rare but serious event following definitive radiation for prostate cancer. Radiation-associated MIBC (RA-MIBC) can be difficult to manage given the challenges of delivering definitive therapy to a previously irradiated pelvis. The genomic landscape of RA-MIBC and whether it is distinct from non-RA-MIBC are unknown.

We identified unique mutational properties that likely contribute to the distinct biological and clinical features of RA-MIBC. Patient summary: Bladder cancer is a rare but serious diagnosis following radiation for prostate cancer. We characterized genetic features of bladder tumors arising after prostate radiotherapy, and identify similarities with and differences from bladder tumors from patients without previous radiation.

To define mutational features of RA-MIBC and compare the genomic landscape of RA-MIBC with that of non-RA-MIBC. Design, setting, and participants: We identified patients from our institution who received radiotherapy for prostate cancer and subsequently developed MIBC. Outcome measurements and statistical analysis: We performed whole exome sequencing of bladder tumors from RA-MIBC patients. Tumor genetic alterations including mutations, copy number alterations, and mutational signatures were identified and were compared with genetic features of non-RA-MIBC. We used the Kaplan-Meier method to estimate recurrence-free (RFS) and overall (OS) survival.