Results of Randomized Trial of Proton and Photon Radiation in Breast Cancer Presented at ASTRO 2025

The first randomized phase III trial comparing proton- and photon-based radiation therapy for breast cancer found that patients reported equally strong quality of life after either treatment. While outcomes were similar, patients treated with proton therapy were more likely to say they would recommend it or choose it again.

The Radiotherapy Comparative Effectiveness (RadComp) trial enrolled 1,239 patients across 32 U.S. centers, making it the largest head-to-head comparison of photon and proton therapy for any cancer. Results were presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

“Patients should feel reassured that they can receive high-quality care with either photon or proton therapy,” said Shannon MacDonald, MD, FASTRO, clinical chair of the trial and medical director at the Southwest Florida Proton Center. “More than a thousand patients in our trial have now shown that, with contemporary treatments, we can deliver curative radiation in a way that preserves multiple aspects of quality of life.”

Patients completed validated questionnaires before, during, and after radiation. Both groups reported equally high physical, social, emotional, and functional well-being, including cosmetic satisfaction.

One difference emerged: patients receiving proton therapy were more likely to report no shortness of breath. However, the effect did not remain statistically significant after adjustment for multiple comparisons. “This finding may still be hypothesis-generating and could warrant future investigations,” Dr. MacDonald noted.

Photon therapy, the standard treatment, uses X-rays to kill residual cancer cells but can expose the heart and lungs to small amounts of radiation. Proton therapy, by contrast, deposits most of its energy directly at the tumor, potentially sparing nearby organs. Access, however, is limited by higher costs and the need for specialized centers.

“Radiation oncologists have debated whether photon or proton therapy is the better choice for treating breast cancer, and there has been little high-quality evidence to guide those decisions,” Dr. MacDonald said.“Quality-of-life research often gets overlooked, but patient-reported outcomes are an essential endpoint for modern trials,” Dr. MacDonald emphasized. “They help us see how well our patients are living after treatment and can also reflect other important outcomes.”