Impact of DNA Repair Deficiency in the Evolving Treatment Landscape of Bladder Cancer

This review explores the current landscape of treatments which target the DNA damage response (DDR) in metastatic and muscle-invasive bladder cancer. It emphasizes recent clinical trials which integrate DDR inhibitors with standard chemotherapy and immunotherapy.

Noteworthy findings include the ATLANTIS trial, which demonstrated prolonged progression-free survival (PFS) in DDR biomarker-selected patients using PARP inhibitors as maintenance after standard chemotherapy. Trials such as BAYOU, which combined immunotherapy with PARP inhibition, similarly suggested a potential therapeutic benefit in DDR biomarker-selected patients with bladder cancer. Efforts to develop bladder-sparing treatment regimens based on DDR-associated mutational profiles, such as the RETAIN and HCRN 16–257 trials, have had mixed outcomes to date. There are now ongoing efforts to combine DDR inhibitors with the newest bladder cancer therapies, such as antibody-drug conjugates.

This review highlights the most recent advances in targeting DNA repair deficiency in the evolving treatment landscape of bladder cancer.