Clinical Summary: 

• Design/Context: This investigational approach combines intraprostatic adenoviral gene therapy with standard radiotherapy in intermediate- and high-risk prostate cancer.
• Key Points: The therapy delivers a replication-deficient adenovirus directly into the prostate to generate local cytotoxic effects and promote immune-mediated antitumor activity.
• Clinical Relevance: This strategy aims to improve long-term outcomes after radiotherapy while minimizing systemic toxicity and reducing recurrence risk.

Mark Garzotto, MD, Oregon Health & Science University, Portland, Oregon, discusses a novel intratumoral adenoviral therapy combined with radiotherapy for patients with intermediate- and high-risk prostate cancer. 

The strategy is designed to enhance radiation sensitivity while stimulating systemic immune responses that may improve long-term disease control.

Dr Gatzotto presented these results at the 2026 American Urological Association (AUA) Annual Meeting in Washington, District of Columbia.

Transcript: 

Good morning, my name is Dr Mark Garzotto. I’m a urologic oncologist at Oregon Health & Science University where I’m a professor of urology and radiation medicine. I’m also a urologist at the Portland VA Medical Center.

In our study, we attempted to try to improve the results of radiation for men with intermediate- and high-risk prostate cancer, which is a very common scenario in clinical practice. Approximately 65,000 men per year are treated with radiotherapy in these clinical scenarios however, the difficulty, or the challenge that arises, is that we know with long-term follow-up 30% or more of these patients will recur. When they recur, we subsequently have to deal with the potential negative consequences of salvage therapies such as hormonal therapy, local treatments including removal of the prostate, as well as re-irradiation.

We tried to improve the upfront results of radiation and do that through sensitizing the radiation and also stimulating the immune system with a novel agent. This agent, known as aglatimagene, is a replication-deficient adenovirus that inserts an enzyme into the tumor cells, which converts a prodrug called valacyclovir into a cytotoxic nucleotide. When this nucleotide is incorporated into the DNA of the tumor cells, it prevents them from replicating and this results in cell death. Once the cells die, within the tumor microenvironment there’s also an immune response that is elicited, which helps not only remove the tumor cells, but also works to promote immune surveillance throughout the body because these T cells, after leaving the prostate gland, circulate throughout the body and work to prevent the cancer from recurring distantly. At least, that is what the preliminary data show for this agent.

A lot of questions that we get are about delivery of the agent, because it is unique, it’s a novel approach. It’s actually an intratumoral injection, the agent gets injected directly into the prostate and this has several advantages. It ensures that the agent is delivered into the prostate at very high concentrations, but it also limits the systemic toxicity or systemic effects that a systemic agent would have. The injections occur in either a urologist’s or radiation oncologist’s office typically, and what it entails is approaching the prostate using ultrasound guidance. This can be done using standard techniques that are already in use in most every urology practice and in many radiation oncology practices. 

Using ultrasound, we use a small spinal needle to inject the agent into the prostate. The prostate gets injected in 4 quadrants, and it’s a total of 2 mL that are injected into the prostate, so half of a milliliter per quadrant. There are 3 injections, which is pretty typical for an effective vaccine strategy, which we feel this models. The first injection occurs about 2 weeks before initiation of standard-of-care radiotherapy, the second injection occurs within a few days of initiation of radiotherapy, and the third injection occurs two weeks after initiation of radiation therapy.

The first injection is typically done in combination with either fiducial seed placement or a rectal spacer, so the patient is already in the office for that visit. This treatment requires just 2 additional visits for this treatment.

Source: 

Garzotto M, Sylvester J, Wheeler T, et al. Extended follow-up shows accumulating benefit for patients treated with aglatimagene besadenovec (CAN-2409)+ prodrug in combination with standard of care external beam radiation (EBRT) in men with localized prostate cancer: Update from a randomized placebo-controlled phase 3 clinical trial. J Urol. Published online: May 1, 2026. doi:10.1097/01.JU.0001192572.07890.f8.01