The American Cancer Society estimates that there will be 233,000 new cases and more than 29,000 deaths from prostate cancer in 2014. Although the disease can be serious, most men will not die from it. More than 2.5 million men in the United States who have been diagnosed with prostate cancer at some point are still alive today. The disease can be managed with a variety of treatments, including watchful waiting, chemotherapy, surgery, brachytherapy, and external beam radiation therapy (EBRT) that is delivered with x-rays or protons. “Treatment selection for prostate cancer is dependent on the extent of the disease, the patient’s overall medical condition, and patient preferences,” says Nancy P. Mendenhall, MD. “Ideally, the goal is to find a treatment that will be highly effective and avoid toxicities.”

The Role of Protons

Radiation therapy is used in two-thirds of cancer patients and is most often delivered with EBRT, a radiation therapy that is produced from a source external to the body. The most common source of radiation in EBRT is x-rays (photons). Most x-ray-based EBRT procedures use sophisticated techniques, such as intensity modulated radiation therapy (IMRT), but there is growing interest in protons as a radiation source. “With proton therapy, a lower radiation dose is deposited in normal non-targeted tissues than with x-rays,” explains Dr. Mendenhall. “This has the potential to reduce toxicity, improve quality of life, and decrease risks for second malignancies. Reducing radiation doses to normal tissues may also permit shorter, less expensive treatment schedules, making proton therapy more convenient for patients.”


Recent studies have shown that men with prostate cancer who are treated with proton therapy alone or in combination with x-ray therapy have had excellent outcomes. Despite these reports, many physicians consider the clinical evidence for proton therapy to be insufficient. Some researchers have relied on surrogate data from Medicare claims to develop comparative studies, making findings somewhat controversial. “All treatment options for prostate cancer have varying toxicity profiles,” adds Dr. Mendenhall. “There is great interest among patients, physicians, insurers, and government agencies to determine the relative effectiveness of various treatments for prostate cancer.”

Long-Term Data

Dr. Mendenhall and colleagues conducted a study that was published in the International Journal of Radiation Oncology*Biology*Physics. The analysis tracked 211 patients who participated in one of three prospective trials in which participants were given proton therapy over 8 weeks. “This treatment interval is shorter than what is typical with IMRT, which may last 9 weeks or longer,” notes Dr. Mendenhall. The study sought to establish benchmark outcomes for proton therapy in low-, intermediate-, and high-risk prostate cancer patients.

In the analysis, researchers used standardized data-gathering methods for both physician- and patient-reported outcomes. The 5-year overall survival rates for low-, intermediate-, and high-risk patients were 93%, 88%, and 86%, respectively (Figure 1). The cancer-free survival rate was 99% for low- and intermediate-risk patients and 76% for high-risk patients (Figure 2). In addition, the rates of serious gastrointestinal and urologic complications from proton therapy were just 1.4% and 5.3%, respectively, for all patients. Study participants receiving proton therapy also reported good urologic and bowel function outcomes.

“Our findings show that the vast majority of men are living free of prostate cancer and have an excellent quality of life at 5 years after having proton therapy,” says Dr. Mendenhall. The data were strongest for those with early- and intermediate-risk prostate cancer but still respectable for men with high-risk disease. These results compare favorably with findings from other intensity modulated radiation therapy studies. In particular, for men with intermediate-risk prostate cancer, the disease control rate has been reported to be between 70% and 85%.

More to Come

The study by Dr. Mendenhall and colleagues adds to the growing body of evidence supporting the role of proton therapy as an effective and efficient treatment option for prostate cancer. “Proton therapy should be considered in the prostate cancer treatment armamentarium because it is highly effective and has minimal toxicity for patients,” says Dr. Mendenhall. “We also observed excellent patient-reported outcomes for bowel and urinary function as well as sexual function.”

Dr. Mendenhall cautions that larger numbers of patients and longer follow-up data on proton therapy are needed to confirm the favorable outcomes observed in the investigation. “Our findings are extremely promising, but many factors may have contributed to our results,” she says. “We hope that more data will further support the use of proton therapy as an effective option to cure the disease without compromising quality of life and possibly decrease the cost of care.” She adds that proton therapy is applicable to many other types of cancer, currently under study at proton centers across the country.


Mendenhall NP, Hoppe BS, Nichols RC, et al. Five-year outcomes from 3 prospective trials of image-guided proton therapy for prostate cancer. Int J Radiation Oncol Biol Phys. 2-14;88:596-602.

Mendenhall NP, Li Z, Hoppe BS, et al. Early outcomes from three prospective trials of image-guided proton therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2012;82:213-221.

Hoppe BS, Michalski JM, Mendenhall NP, et al. Comparative effectiveness study of proton therapy versus IMRT for definitive treatment of prostate cancer based on patient-reported outcomes. Int J Radiat Oncol Biol Phys. 2013;87:S346.

Sheets NC, Goldin GH, Meyer AM, et al. Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer. JAMA. 2012;307:1611-1620.