Novel neoadjuvant therapy paradigms for bladder cancer: results from the National Cancer Center Institute Forum.

Objective: To bridge gaps in translational science and develop the concepts for 2 novel biomarker-driven clinical trials: one in the presurgical setting and the other in the setting of bladder preservation with chemoradiation.

Methods And Materials: The National Cancer Institute sponsored a forum, "Novel Neoadjuvant Therapy for Bladder Cancer," which brought leading clinical and laboratory-based scientists together with the advocacy community.

Results: The group designed a neoadjuvant clinical trial to compare the clinical efficacy of the two frontline chemotherapy regimens (gemcitabine plus cisplatin versus MVAC) and the ability of a gene expression profiling-based algorithm (CoXEN) to predict complete pathological response. The trial was recently opened under the leadership of the Southwest Oncology Group (SWOG, S1314), receiving support for the biomarker studies from the NCI's BISQFP resource. A second clinical trial was planned that will examine the relationship between expression of the DNA repair protein MRE11 and complete response in patients treated with concurrent 5-fluorouracil/mitomycin C plus radiation.

Conclusion: The meeting provided a unique opportunity to launch a collective effort to establish molecular-based therapies for muscle-invasive urothelial cancer. The goal is to use this framework to develop comparable trials with immunotherapy in non-muscle invasive cancers and to exploit the neoadjuvant platform to develop targeted therapy in muscle-invasive disease.