Dear Colleagues,

Bladder cancer is one of the most frequently diagnosed neoplasms, and there were nearly 600,000 new cases and 220,000 deaths from it, suggesting that controversial treatments have some problems in bladder cancer. Although radiotherapy combined with chemotherapy has been shown to offer a survival benefit comparable to that of radical cystectomy (RC) with chemotherapy in muscle-invasive bladder cancer (MIBC), RC has still been the main treatment in MIBC. There are some reasons why RC remains the main treatment for it. First of all, the success rate of radiotherapy is insufficient, although it is comparable to RCs. Secondly, adverse effects such as radiation cystitis and proctitis are sometimes critical. Finally, RC after radiotherapy is more invasive because the risk of complications is higher compared to primary cystectomy. Thus, identifying a key target to overcome radioresistance and predict prognosis is warranted. Recent evidence suggested that the signaling of sex steroid hormonal receptors, including androgen, was strongly involved in the carcinogenesis and progression of bladder cancer. More recently, it has been shown that modification of these signaling pathways has the potential to enhance the sensitivity of radiotherapy. Specifically, this signaling was highly associated with DNA repair genes. Moreover, some molecules related to hypoxia and immune activation have the potential to enhance the sensitivity to radiation in bladder cancer. Additionally, the radio sensitivity might depend on molecular subtypes (basal, luminal, and p53-like luminal) in MIBC.   Therefore, we believe that exploring the novel target and summarizing the recent evidence helps MIBC patients select appropriate treatment and contributes to their prognostic improvement.