Proton Beam Therapy and Treatment for Localized Prostate Cancer: If You Build It, They Will Come

The number of treatment options for localized prostate cancer continues to expand, amidst growing concern regarding overdiagnosis and overtreatment of low-risk disease.^1-3 Treatment patterns, however, may be driven by availability of novel technologies rather than by clinical indications. We aimed to examine regional treatment choices of men diagnosed as having localized prostate cancer living inside or outside of a defined hospital referral region containing a proton beam cyclotron in California.

We performed a retrospective cross-sectional analysis of men with prostate cancer identified through the California Cancer Registry from 2003 to 2006. Inclusion criteria were low- to intermediate-risk prostate cancer, defined by clinical stage (≤T2c) and well- to moderately differentiated histology (Gleason score ≤7). Patients were grouped according to their hospital referral region (HRR) at time of diagnosis, as defined by the Dartmouth Atlas group (http://www.dartmouthatlas.org).⁴ In brief, HRRs represent regional health care markets for tertiary medical care. Four HRRs extending into neighboring states were excluded.

Our primary predictor was a binary variable signifying whether a man was living in the HRR for San Bernardino, California (SBHRR), where the proton beam facility resides at Loma Linda University. The primary dichotomous outcome was prostate cancer treatment by proton beam therapy vs treatment by other modalities (including active surveillance). Prostate cancer treatment patterns were analyzed by HRR using logistic regression models. All candidate predictors were included in a multivariable model, including age, tumor grade, stage of cancer, race/ethnicity, year of diagnosis, and residence in the SBHRR. Statistical analyses were performed using SAS v9.2 software (SAS Institute Inc). The institutional review board at the University of California, San Francisco, approved the study.

A total of 19 816 patients met inclusion criteria. Mean age and tumor stage were similar for those living in or outside the SBHRR. The SBHRR had the highest rate of proton beam therapy compared with the rest of California (8.5% vs 1.7%; Figure). Mean (SD) proton beam therapy rate was 2.3% (1.4%), and the range of patients treated by HRR was 0 to 142 for this period. Redding HRR showed the next highest rate of proton beam therapy; however, 184 patients were from that HRR, so this rate is based on only 13 patients receiving this treatment.

Patients living in the SBHRR were more likely to be treated with the proton beam therapy than if they lived outside of the SBHRR in univariate analysis (odds ratio [OR], 5.3; 95% CI, 4.3-6.5 [P < .001]). In multivariate analysis controlling for tumor stage, grade, race, year of diagnosis, and age, residence within the SBHRR remained independently predictive of receiving treatment with a proton beam compared with those outside the HRR (OR, 5.5; 95% CI, 4.5-6.8 [P < .001]). Patient age and non-Hispanic white ethnicity remained significantly independently associated with either a lower (age: OR, 0.98; 95% CI, 0.97-0.99 [P < .001]) or a higher (non-Hispanic white: OR, 2.1; 95% CI, 1.7-2.7 [P < .001]) likelihood of receiving proton beam therapy.

No prostate cancer treatment has been proven superior to the others.⁵ There are, however, substantial differences in cost, which are becoming more important to society and are a focus of health care reform in the United States.^6,7 While there are theoretical advantages to proton beam therapy from a radiation physics standpoint, no study yet has demonstrated its superiority to modern photon-based therapy in terms of either oncologic or quality of life outcomes.^8,9 To our knowledge, we show for the first time that the availability of a technology, in this instance a proton beam facility, in one's HRR is associated with a higher likelihood of receiving proton beam therapy compared with those living in an HRR where this technology is not available. A single physician might explain the higher-than-expected rate of proton beam therapy in the Redding, California, HRR, since there are relatively low numbers of overall patients from this area. Interestingly, self-description as non-Hispanic white was also associated significantly with increased odds of receiving proton therapy—hinting at a possible racial disparity requiring further investigation.

There were several limitations: (1) Our prostate cancer risk stratification does not include prostate-specific antigen levels or Gleason scores because these are not included in the CCR. (2) Unmeasured confounding may exist, but the association of living in the SBHRR and receiving proton beam therapy is large. (3) Registry data are limited in clinical detail and may be biased through underreporting. However, there should not be systematic bias as the unreported cases are likely to have the same treatment distribution as the reported cases.

Proton beam therapy has not been shown to be superior to other treatments for prostate cancer and is substantially more expensive.⁷ Caution should be taken when considering implementation of this technology in additional regions, which may lead to greater use of this technology.

Correspondence: Dr Aaronson, Department of Urology, The Kaiser Permanente Medical Group, 280 W MacArthur Blvd, Oakland, CA 94611 (David.S.Aaronson@kp.org).

Author Contributions:Study concept and design: Aaronson, Odisho, Carroll, Dudley, and Cooperberg. Acquisition of data: Aaronson and Cress. Analysis and interpretation of data: Aaronson, Odisho, Hills, Carroll, Dudley, and Cooperberg. Drafting of the manuscript: Aaronson, Hills, and Dudley. Critical revision of the manuscript for important intellectual content: Odisho, Cress, Carroll, Dudley, and Cooperberg. Statistical analysis: Odisho and Hills. Obtained funding: Aaronson. Administrative, technical, and material support: Carroll and Dudley. Study supervision: Cress, Carroll, Dudley, and Cooperberg.

Funding/Support: This study was funded by a University of California, San Francisco, Clinical & Translational Science Resident Research Grant and was additionally supported by grant 1R01HS019356-01 from the National Institutes of Health. The collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. From the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, funding was awarded to the Northern California Cancer Center contract N01-PC-35136, to the University of Southern California under contract N01-PC-35139, and to the Public Health Institute under contract N01-PC-54404. From the Centers for Disease Control and Prevention's National Program of Cancer Registries, funding was awarded to the Public Health Institute under agreement 1U58DP00807-01.

Disclaimer: The ideas and opinions expressed herein are those of the authors and endorsement by the State of California, Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended nor should be inferred.