Where Does Intensity-Modulated Proton Therapy Fit in Prostate Cancer?

Intensity-modulated proton therapy (IMPT) allows radiation oncologists to limit the dose to organs surrounding the prostate. That property may be particularly relevant for patients with prostate cancer who require pelvic nodal irradiation. At the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting, investigators from Baptist Health Herbert Wertheim Cancer Institute (WCI) reported disease control outcomes among 404 patients with intermediate- to very high–risk localized prostate cancer treated with IMPT between 2018 and December 2023. With a median follow-up of more than 4 years, recurrences were rare in intermediate-risk disease and somewhat more frequent in high- and very high–risk disease.

CancerNetwork® spoke with Marcio A. Fagundes, MD, vice chair of Radiation Oncology, director of International Outreach, and a radiation oncologist at Baptist Health Herbert WCI in Miami, Florida, who presented the findings.

Fagundes began by describing disease control across risk groups and the role of pelvic nodal irradiation in higher-risk patients. He then discussed how androgen deprivation therapy (ADT) is used alongside radiation and how proton therapy and rectal spacers can reduce toxicity. Next, he explained which clinical scenarios most strongly justify choosing proton therapy over photon-based approaches such as stereotactic body radiotherapy (SBRT). He concluded by outlining a planned multi-institutional study focused on quality-of-life end points.

CancerNetwork: How did biochemical relapse-free survival and overall disease control compare across the intermediate-, high-, and very high–risk cohorts in your study of IMPT?

Fagundes: When we talk about biochemical disease control, we are talking about patients with prostate cancer whom we treat and whose prostate-specific antigen [PSA] goes down and does not come back up. Biochemical recurrence is defined as a rise in PSA that may be caused by recurrence of cancer. In a patient who is treated successfully, we expect the PSA to remain low. In patients with favorable intermediate- or unfavorable intermediate-risk disease, the results are generally better, with a better than 90% chance of remaining free of disease recurrence. In patients with high-risk or very high–risk disease, the recurrence risk may be in the range of 10% to 20%.

This is not a comparative study against patients who did not receive protons. This study reports on WCI’s experience treating patients with prostate cancer with proton therapy between 2018 and December 2023. This is the first report of the initial 404 patients, all of whom were treated with proton therapy.

What is interesting is that among patients with high-risk and very high–risk disease, a substantial number, the majority, also received pelvic nodal radiation as part of their treatment. That is because these patients have an increased risk of cancer spreading to the lymph nodes. Proton therapy can treat the pelvic lymph nodes without really increasing the risk of adverse effects [AEs] like diarrhea. The treatment is safer in that sense, and we are giving the same effective dose as you would with conventional radiation, which is intensity-modulated photon radiation.

How is ADT used alongside radiation across these risk groups?

When we talk about systemic treatments, or additional treatments other than the radiation delivered with protons, we are talking about ADT, which is blocking testosterone. In patients with unfavorable intermediate-risk disease, there are data showing that adding 6 months of ADT improves the chances that the patient will never have a recurrence.

In patients with high-risk disease, studies are now trying to use [fewer] than 18 to 24 months of ADT. But most patients currently still receive 18 to 24 months of testosterone blockade along with radiation for high- or very high–risk disease. Adding testosterone blockade improves the chances of patients never having a recurrence.

Given the sharp distal dose falloff of proton beams, what AEs do you expect to avoid, and how are rectal spacers used to reduce doses to the rectum?

Proton therapy has a unique property: the beam goes in and stops at a depth in the body that we can control. With proton therapy, we are decreasing the exposure of the intestines and bladder, for example, to doses of radiation that you do not really need to deliver. You can reduce the dose with proton therapy, and we do expect that AEs will be reduced. In this report, we focused on disease control, but in the next report I am working on, we are comparing AEs in patients treated with vs without a rectal spacer.

What is a rectal spacer? It is a device that we inject between the rectum and the prostate to push the rectum away from the prostate. That decreases the amount of radiation the rectum receives and makes the radiation treatment safer. Most patients are candidates for a rectal spacer. Some patients may have tumors infiltrating the capsule of the prostate, right where the rectum is, and these patients are not candidates for rectal spacer placement.

For most patients, though, the radiation dose is lower because we move the rectum away, and the treatment is safer. Patients virtually never have AEs like irritation of the rectum, called proctitis, which could cause rectal bleeding similar to a hemorrhoid. That goes away, but we can prevent it by using a rectal spacer.

For multidisciplinary tumor boards weighing IMPT against advanced photon-based modalities such as ultrahypofractionated SBRT or volumetric modulated arc therapy, what scenarios in intermediate- to very high–risk disease provide the strongest justification for prioritizing proton therapy?

Prioritizing proton therapy is most justified, or easiest to demonstrate, when we are treating the pelvic lymph nodes. Current practice guidelines determine that we have to include the lymph nodes up to the iliac bifurcation, which is usually at the L4 or L5 level. That includes a significant extent of the pelvis; virtually the entire pelvic nodal chain is included. Proton therapy will decrease doses to the bowel and minimize AEs. That is the justification for using it.

SBRT involves only 5 sessions, given every other day, for example. It is primarily recommended for low- and intermediate-risk prostate cancer, not for patients in whom we are treating the pelvic nodes. When you are treating pelvic nodes, doing 5 fractions is still a developing paradigm. We are primarily treating patients with low- and intermediate-risk disease in 5 sessions, not those who need pelvic lymph node treatment.

What study is needed next to define the true benefit of IMPT?

One of the studies we are looking into, which would become a multi-institutional study, examines which end points make the most sense to measure when we treat the pelvic lymph nodes with proton therapy compared with conventional radiation. Is it chronic diarrhea? Is it changes in bowel habits that would bother a patient’s quality of life?

Ultimately, we have to look at quality of life because we are not just treating the cancer; we are treating the patient. We have to cure and eliminate the cancer but, at the same time, do our best not to change patients’ quality of life from where it was before they started treatment. We are looking at any increased frequency of diarrhea, irregular bowel movements, and urgency to have a bowel movement.

All these factors matter, and I believe proton therapy is a tool that could reduce the risk of these changes. That is what we are looking for: to eradicate the cancer without changing patients’ quality of life.

References

Fagundes MA, Hassan H, Rodrigues M-A, et al. Intensity modulated proton therapy (IMPT) for localized prostate cancer: disease control outcomes in intermediate to very-high risk patients. Presented at: 2026 ASTRO Annual Meeting; September 26-30, 2026; Boston, MA. Abstract PQA 06.