Landmark Trial Finds Comparable Quality of Life With Proton and Photon Therapy for Breast Cancer

The first randomized trial directly comparing photon- and proton-based radiation therapy for breast cancer has found that patients report similarly strong health-related quality of life with either treatment. While those who received proton therapy were slightly more inclined to recommend or choose it again, overall outcomes related to well-being and satisfaction did not differ significantly between the two groups.

These early results come from the Radiotherapy Comparative Effectiveness (RadComp) trial, the largest head-to-head study of its kind for any cancer, with more than 1,200 patients enrolled across 32 U.S. centers. Findings were presented this week 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.”

Breast cancer remains the most frequently diagnosed cancer among women in the U.S., with over 320,000 cases expected in 2025. For patients with locally advanced disease—where cancer has spread to nearby lymph nodes or chest wall but not beyond—treatment often involves surgery followed by external-beam radiation therapy. Radiation plays a key role in reducing recurrence and extending survival, but questions remain about the best way to deliver it.

Photon therapy, the current standard, uses X-rays to destroy residual cancer cells after surgery. While highly effective, photons can expose nearby organs such as the heart and lungs to low doses of radiation, potentially contributing to cardiac or pulmonary complications over time. Proton therapy, by contrast, uses charged particles that deposit most of their energy at the tumor site and stop there, limiting radiation “spillover” to adjacent organs. Access to proton facilities is still limited, however, and treatment costs remain considerably higher.

The RadComp trial was designed to evaluate whether proton therapy could offer measurable benefits over photons in terms of toxicity, long-term outcomes, and patient experience. The current analysis focused on patient-reported quality of life.

Of the 1,239 patients enrolled, roughly half received proton therapy (624) while the remainder were treated with photons (615). Most participants were around 50 years old, with the majority having undergone mastectomy and receiving treatment for left-sided or bilateral disease. All patients were treated to the internal mammary lymph nodes, a common site of recurrence risk.

Participants completed validated questionnaires before starting treatment, at the conclusion of radiation, and at one and six months afterward. Responses covered physical symptoms, emotional well-being, social functioning, cosmetic outcomes, and treatment satisfaction.

Across nearly all measures, patients in both arms reported equally favorable outcomes. One signal that emerged—fewer reports of shortness of breath among proton-treated patients—did not remain statistically significant after correcting for multiple comparisons. Both groups had very few patients reporting moderate or severe symptoms.

Notably, patients who received proton therapy were more likely to say they would recommend the treatment or choose it again. Dr. MacDonald suggested that this difference may be influenced by perceptions of proton therapy as newer or more advanced technology, rather than by measurable differences in quality of life.

Future analyses from RadComp will address long-term endpoints, including whether proton therapy reduces cardiac events while preserving cancer control. These results are expected in the coming years. For now, the data provide reassurance that both photon and proton therapy remain high-quality options for patients with breast cancer.