Proton therapy (PT) is an advanced form of radiation therapy that exploits the physical properties of the Bragg peak to deliver highly conformal dose distributions while minimizing radiation exposure to surrounding normal tissues. This precision is particularly relevant in prostate cancer, where critical organs at risk, including the rectum, bladder, bowel, and penile bulb, are in close proximity to the target. This review summarizes the evolution of PT techniques for prostate cancer, from early passively scattered proton therapy (PSPT) to contemporary intensity-modulated proton therapy (IMPT), and evaluates their dosimetric and clinical implications across multiple treatment settings. Dosimetric studies consistently demonstrate that PT, particularly IMPT, reduces integral dose and improves normal tissue sparing compared with photon-based modalities (XRT) such as intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), especially in low- to intermediate-dose regions. These advantages are most pronounced for complex target volumes, including pelvic nodal irradiation and focal intraprostatic boosting. Clinical outcomes data for prostate only treatment indicate excellent disease control with low rates of high grade gastrointestinal and genitourinary toxicity. Emerging evidence suggests potential benefits of PT in reducing specific rectal symptoms and lowering the risk of secondary malignancies. For high-risk prostate cancer requiring pelvic irradiation, prospective and registry-based studies demonstrate favorable toxicity profiles with IMPT, supporting its use in extended treatment fields. In the postoperative setting, PT offers dosimetric improvements, though clinical benefits over XRT remain less clearly defined. Additionally, these advancements in technology have allowed for more precise hypofractionated treatment, including proton stereotactic body radiation therapy, without significant increases in genitourinary or gastrointestinal toxicity. Finally, ultra-high dose rate FLASH PT may further enhance the therapeutic ratio. Overall, modern PT represents a highly precise and evolving modality in prostate cancer management, with the potential to optimize oncologic outcomes while preserving long-term quality of life. Further randomized and cost effectiveness studies are needed to fully define its role relative to advanced photon techniques.
Frontiers in oncology. 2026 Apr 17*** epublish ***
Irini Yacoub, Joshua Khalil, Shouyi Wei, Kristin Hsieh, Arpit M Chhabra, Keyur J Mehta, Caroline Oska, Lifei Zhu, Jehee Isabelle Choi, Charles B Simone
New York Proton Center, New York, NY, United States., Department of Biological Science, University of California San Diego, La Jolla, CA, United States., Department of Radiation Oncology, Montefiore Einstein Cancer Center, New York, NY, United States.