Letter to the JAMA Editor

Radiation Therapy Modalities for Prostate Cancer

August 1, 2012

NAPT supports this AUGUST 1st Letter to the JAMA editor responding to an article about prostate cancer. Proton therapy remains a viable treatment option for patients seeking  to minimize side effects and morbidity resulting in better quality of life outcomes. 

To the Editor:
Dr Sheets and colleagues1 used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to retrospectively compare surrogate outcomes (claims) for patients with non–metastatic prostate cancer treated with 3 radiation modalities—conformal radiation therapy, IMRT, and proton therapy—advances expected to improve disease control and toxicity outcomes through improved radiation dose distribution.

The authors characterized the SEER-Medicare data as " . . . a large population-based sample and are therefore more likely to reflect results from treatments widely available in the community . . . ." More than 12 000 geographically distributed patients receiving IMRT and conformal radiation therapy were included, and that statement might be correct for these therapies. However, there are significant limitations of the SEER-Medicare database in the evaluation of proton therapy. Only 684 patients receiving proton therapy were identified, and the authors failed to disclose that all were treated at a single institution, Loma Linda University Medical Center—the only proton facility treating patients with prostate cancer and submitting data to the SEER registry during the timeframe of the study. Although the thors performed a propensity score adjustment, that is insufficient to eliminate single institution bias—particularly with respect to radiation dose, a key predictor for both disease control and toxicity, and surrogate outcomes (eg, proactive surveillance with assessments such as colonoscopy).

From 2002-2007, patients from Loma Linda were treated with aggressive protocols with dose-escalated radiotherapy (doses of 79.20 Gy to 82 Gy, later proven beneficial for biochemical freedom from prostate cancer) and up
to 30% of patients receiving proton therapy also received doses of 45 to 50 Gy with photons (x-rays). 2 Typical community conformal radiation therapy and IMRT practice during this time involved significantly lower radiation doses at
or below 75 Gy to avoid toxicity.

In addition, the authors failed to account for the significant discrepancy between toxicity rates for proton therapy implied by outcome surrogates (ie, claims for colonoscopy procedures) and the published grade 3gastrointestinal and genitourinary complication rates of 2% or less for patients treated with up to 80 CGE (cobalt Gy equivalent) reported from Loma Linda and other proton facilities.2,3 Community practice at the time did not involve routine prospective
toxicity tracking with colonoscopy.

Therefore, the conclusion that proton therapy is more toxic and no more effective than IMRT in the treatment of prostate cancer should not be drawn unless similar doses and optimized surveillance techniques for both modalities are compared.

Nancy P. Mendenhall, MD
Steven Schild, MD
Jerry Slater, MD

Author Affiliations: University of Florida Proton Therapy Institute, Jacksonville, Florida (Dr Mendenhall;; Mayo Clinic, Rochester, Minnesota (Dr Schild); and Loma Linda University Medical Center, Loma Linda, California (Dr Slater).

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors are members of the Medical Leadership of the Proton Therapy Consortium, a nonprofit corporation whosemission is to ensure that patients have access to proton therapy.

1. 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(15):1611-1620.
2. Slater JD, Rossi CJ Jr, Yonemoto LT, et al. Proton therapy for prostate cancer: the initial Loma Linda University experience. Int J Radiat Oncol Biol Phys. 2004; 59(2):348-352.
3. 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 BiolPhys. 2012;82(1):213-221.


> Send mail to with questions or comments about this web site.