Immunomodulation Plus IMRT in Intermediate and High-Risk Prostate Cancer: Phase III Randomized Trial

How to cite: Sylvester JE. “Immunomodulation Plus IMRT in Intermediate and High-Risk Prostate Cancer: Phase III Randomized Trial.” October 23, 2025. Accessed Oct 2026. https://grandroundsinurology.com/immunomodulation-plus-imrt-in-intermediate-and-high-risk-prostate-cancer-phase-iii-randomized-trial/

Summary

John E. Sylvester, MD, FABS, Radiation Oncologist, Atlantic Urology Specialists, Myrtle Beach, South Carolina, reviews a large phase III randomized trial evaluating the addition of intraprostatic immunomodulation to intensity-modulated radiation therapy (IMRT) for intermediate- and high-risk localized prostate cancer. Dr. Sylvester presents the rationale, mechanism, and clinical outcomes of combining CAN-2409 with standard external beam radiation therapy, with or without short-term androgen deprivation therapy.

CAN-2409 is a replication-defective adenoviral vector carrying the herpes simplex virus thymidine kinase gene. When injected into the prostate and combined with oral valacyclovir, the system induces selective tumor cell death and generates an inflamed tumor microenvironment that promotes systemic immune activation. Radiation further enhances this effect.

The phase III trial enrolled 745 patients across 51 centers in the United States and Puerto Rico, with randomization in a 2:1 ratio to CAN-2409 plus standard-of-care radiation versus placebo plus radiation. Intermediate-risk disease accounted for the majority of enrolled patients, with balanced use of androgen deprivation therapy (ADT) between arms. The median follow-up exceeded 50 months.

Results demonstrate a 30% relative risk reduction in disease recurrence or death among patients receiving CAN-2409. Prostate cancer–specific disease-free survival improved with a 38 percent relative risk reduction. Secondary endpoints favored CAN-2409, including higher rates of prostate-specific antigen (PSA) nadir below 0.2 ng/mL and significantly higher rates of negative prostate biopsy at two years. Overall survival was similar between groups at current follow-up.

Treatment was well tolerated. Transient flu-like symptoms were more common in the CAN-2409 arm, while serious adverse events and treatment discontinuation rates were comparable or numerically lower. Dr. Sylvester positions this immunomodulatory strategy as a meaningful advance in localized prostate cancer, demonstrating disease-free survival improvement not previously achieved with radiation intensification alone.

About the 28th Annual Southwest Prostate Cancer Symposium:

Presented by Program Chairs Nelson N. Stone, MD, Richard G. Stock, MD, and William K. Oh, MD, this conference educated attendees about advances in the management of localized and advanced prostate cancer, with a focus on imaging, technology, and training in the related devices. It included a scientific session, as well as live demonstrations of surgical techniques.