Adjuvant treatment following radical cystectomy for muscle-invasive urothelial carcinoma and variant histologies: Is there a role for radiotherapy?

Comprehensive molecular characterisation of muscle-invasive urothelial carcinoma and variant histological subtypes has led to the identification of recurrent driver mutations that are distinct in these aggressive subgroups of bladder cancer. While distant metastasis dominates as a pattern of relapse following radical cystectomy or chemoradiotherapy, loco-regional control rates are also suboptimal with single modality local treatment, and likewise, harbour equivocal implications on the long-term prognosis of patients. The role of adjuvant radiotherapy for optimising disease control within the pelvis is controversial, with limited evidence to support its efficacy. Herein, we present a stepwise review on adjuvant radiotherapy post-cystectomy; first, discussing the evidence to date supporting the concept that adjuvant radiotherapy is effective in targeting occult metastases within the pelvis, and adds to the benefits of adjuvant chemotherapy. Next, we outlined the principles underlying the definition of radiotherapy target volumes. To conclude, we addressed the need for appropriate patient stratification for treatment intensification, based on existing clinical models and novel molecular indices of aggression in muscle-invasive urothelial cancers and variant histological subtypes.