Predicting Complete Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

Simple Summary Bladder cancer is the second most common urologic malignancy. Current standard of care for muscle-invasive bladder cancer is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy. There is an unmet need to predict which patients will benefit from neoadjuvant chemotherapy as treatment results in toxicities associated with therapy as well as delays to radical cystectomy. This review summarizes several predictors of complete response to neoadjuvant chemotherapy as well as current clinical trials to aid urologists and oncologists treating bladder cancer. Muscle-invasive bladder cancer is a life-threatening disease best managed with multimodal therapy. Neoadjuvant chemotherapy prior to cystectomy significantly improves survival with the greatest benefit noted in patients with a complete pathologic response noted at cystectomy. While radical cystectomy is currently an important part of the treatment plan, surgical morbidity remains high. Accurate prediction of complete responses to chemotherapy would enable avoiding the morbidity of radical cystectomy. Multiple clinical, pathologic, molecular, and radiographic predictors have been evaluated. Clinical and standard pathologic findings have not been found to be accurate predictors of complete response. To date, tumor genomic findings have been the most promising and have led to multiple clinical trials to evaluate if bladder preservation is possible in select patients. Radiomics has shown initial promise with larger validation series needed. These predictors can be further characterized as treatment specific and non-treatment specific. With the potential changing landscape of neoadjuvant therapy prior to radical cystectomy and the limitations of individual predictors of a complete response, a panel of several biomarkers may enhance patient selection for bladder preservation. The aim of this review is to summarize predictors of complete response to neoadjuvant chemotherapy.