No difference in toxicity observed between proton radiotherapy, IMRT

Yu JB. J Natl Cancer Inst. 2012;doi:10.1093/JNCI/djs639.

  • HemOnc Today, February 25, 2013

Proton radiotherapy is approximately 70% more expensive than intensity-modulated radiotherapy, but researchers found no difference in toxicity between the two prostate cancer treatments, according to results of a retrospective study.

IMRT is considered the standard form of radiotherapy for patients with prostate cancer. Proton radiotherapy is an emerging treatment option, but researchers possess limited knowledge of the clinical benefits or potential adverse events associated with this approach, according to background information in the study.

In the current investigation, researchers compared the patterns of use, cost and early toxicity of IMRT vs. proton radiotherapy among Medicare beneficiaries with prostate cancer.

James B. Yu, MD, assistant professor of therapeutic radiology at Yale University School of Medicine, and colleagues performed a retrospective study on all Medicare beneficiaries aged at least 66 years who received proton radiotherapy or IMRT for prostate cancer during 2008 and/or 2009.

To assess toxicity, researchers matched each proton radiotherapy patient with two IMRT patients with similar clinical and sociodemographic characteristics. Receipt of proton radiotherapy or IMRT, Medicare reimbursement for each treatment and early genitourinary, gastrointestinal and other toxicities served as the main outcome measures.

Of the 27,647 men identified by Yu and colleagues, 553 (2%) underwent proton radiotherapy and 27,094 (98%) underwent IMRT. Patients who received proton radiotherapy were younger, healthier and from more affluent areas than patients treated with IMRT, study results showed.

The median Medicare reimbursement for proton radiotherapy was $32,428 vs. $18,575 for IMRT.

At 6 months, proton radiotherapy was associated with significant reduction in genitourinary toxicity (5.9% vs. 9.5%; OR=0.6; 95% CI, 0.38-0.96), study results showed. However, at 12 months post-treatment, there was no difference in genitourinary toxicity (18.8% vs. 17.5%; OR=1.08; 95% CI, 0.76-1.54).

Researchers observed no statistically significant difference in gastrointestinal or other toxicity at 6 or 12 months after treatment.

“This study represents the most robust comparison of early toxicity for proton radiotherapy vs. IMRT for prostate cancer to date,” Yu and colleagues wrote. “In a national sample of Medicare beneficiaries, [proton radiotherapy] was rare and expensive and associated with only a modest and transient reduction in genitourinary toxicity.”

Continued longitudinal study on the effectiveness of proton radiotherapy compared with IMRT is needed, Yu and colleagues concluded.

In an accompanying editorial, Justin E. Bekelman, MD, assistant professor of radiation oncology in the department of radiation oncology at the Hospital of the University of Pennsylvania, and Stephen M. Hahn, MD, chair and Henry K. Pancoast professor of radiation oncology at the University of Pennsylvania School of Medicine, called the study by Yu and colleagues an example of “careful observational comparative effectiveness research,” but they still urged caution.

“Without studies to validate the surrogacy of claims-based endpoints, outcome misclassification could lead to false-negative or false-positive results,” Bekelman and Hahn said.

In another editorial, Theodore S. Lawrence, MD, PhD, professor of radiation oncology at the University of Michigan, and Mary Feng, MD, assistant professor of radiation oncology at the University of Michigan, said although it is unlikely that proton therapy will be superior to IMRT photons for prostate cancer, protons may be superior for lung cancers when combined with chemotherapy.

“However, this is a hypothesis that must be tested,” Lawrence and Feng wrote. “Declaring that proton therapy is new, awarding it high reimbursements and stating that it has theoretical dosimetric advantages over photons is not acceptable. We need prospective clinical trials directly comparing protons to IMRT photons.”

Disclosure: Bekelman, Feng, Hahn, Lawrence and Yu report no relevant financial disclosures.

Perspective

Derek Raghavan

  • The article by Yu and colleagues addresses an important topic — namely, an attempt to work out whether proton radiotherapy (PRT) is truly superior to IMRT. Of course, before discussing this study, we shouldn't forget that Schulz and Kagan have questioned whether IMRT is truly superior to conventional external beam therapy for prostate cancer when one looks at the big picture of cost and efficacy.

    I applaud anyone who takes the trouble to try to ask questions about the true utility of PRT for prostate cancer. After decades of PRT development, we still don't know the answer, which really is a disgrace, reflecting poorly on the proton beam "industry" and its early developers. The data that Yu et al have produced, which seriously question whether there are 12-month toxicity-related benefits from PRT, are important and thought provoking. However, retrospective, post-hoc analyses of large, cleaned data sets represent a very poor surrogate for real, level 1, randomized clinical trial data. There are many variables of case and treatment selection bias that can creep into such analyses, as acknowledged by Yu and colleagues, and we must be careful not to confuse this analysis with real-time data.

    This study also raises questions about clinical common sense in the United States. Did anyone notice how many patients received either IMRT or PRT when they were over the age of 85 years? What about the discrepancy between whites and African Americans, and rich vs. poor? It's hard to be proud of our system when so many inequities are still present. I wonder when we will get past the analysis paralysis and actually do something about these issues as a health care system. Watching the shenanigans in Congress and the Senate these past weeks, I doubt that it will be soon.

    • Derek Raghavan, MD, PhD, FACP, FRACP, FASCO
    • HemOnc Today Editorial Board member