Oncolytic virus therapy for nonmuscle-invasive bladder cancer: current status and future directions.

Purpose of review: Nonmuscle-invasive bladder cancer (NMIBC) patients with BCG-unresponsive disease have limited treatment options beyond radical cystectomy. With ongoing BCG shortages and the urgent need for bladder-preserving alternatives, this review examines the emerging role of oncolytic virus therapy as a novel intravesical treatment approach for this challenging patient population.

Recent findings: Multiple oncolytic viral platforms have entered clinical trials for NMIBC treatment, demonstrating promising efficacy and safety profiles. Cretostimogene grenadenorepvec has shown exceptional results in a phase 3 trial, achieving 74.5% complete response rates with durable responses exceeding 27 months in BCG-unresponsive carcinoma in situ. Combination therapy with pembrolizumab further enhanced efficacy, with a 57.1% complete response rate at 12 months and no progression to muscle-invasive disease. Other viral platforms, including herpes simplex, coxsackie, and measles viruses, have demonstrated preliminary antitumor activity with favorable safety profiles. These agents utilize three mechanisms of action: selective viral replication, direct oncolysis, and immune system activation.

Summary: Oncolytic virus therapy represents a paradigm shift toward an effective bladder-preserving treatment for BCG-unresponsive NMIBC. With phase 3 data supporting regulatory approval pathways, these therapies are poised to become new standards of care, offering hope for improved outcomes while avoiding radical surgery.