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

Area of Science:

• Oncology
• Virology
• Immunotherapy

Background:

• Nonmuscle-invasive bladder cancer (NMIBC) patients with BCG-unresponsive disease face limited treatment options.
• Radical cystectomy is often the only alternative, highlighting the need for bladder-preserving strategies.
• Ongoing Bacillus Calmette-Guérin (BCG) shortages exacerbate the demand for novel therapies.

Purpose of the Study:

• To review the emerging role of oncolytic virus therapy for BCG-unresponsive NMIBC.
• To examine novel intravesical treatment approaches for this patient population.
• To assess the potential of oncolytic viruses as bladder-preserving alternatives.

Main Methods:

• Review of clinical trials involving oncolytic virus platforms for NMIBC.
• Analysis of efficacy and safety data from phase 3 trials, including cretostimogene grenadenorepvec.
• Examination of combination therapy outcomes and other viral platforms (herpes simplex, coxsackie, measles viruses).

Main Results:

• Multiple oncolytic viral platforms show promising efficacy and safety in NMIBC clinical trials.
• Cretostimogene grenadenorepvec achieved 74.5% complete response rates in BCG-unresponsive carcinoma in situ.
• Combination therapy with pembrolizumab demonstrated a 57.1% complete response rate at 12 months, preventing progression to muscle-invasive disease.

Conclusions:

• Oncolytic virus therapy represents a paradigm shift for bladder-preserving treatment in BCG-unresponsive NMIBC.
• Phase 3 data support regulatory approval, positioning these therapies as potential new standards of care.
• These novel treatments offer hope for improved outcomes and avoidance of radical surgery.