JAMA: Proton therapy for prostate cancer may not live up to hype
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Treatment of localized prostate cancer with intensity-modulated radiation therapy (IMRT) may provide improved disease control with less morbidity than conformal radiation therapy, according to an analysis published April 17 in the Journal of the American Medical Association. However, proton therapy did not appear to provide additional benefits for these patients.

Treatment of localized prostate cancer is a “first quartile” priority topic on the Institute of Medicine’s top 100 topics for comparative effectiveness research. More than 200,000 men in the U.S. are diagnosed annually with prostate cancer, and newer treatments with unproven clinical benefits such as IMRT and proton therapy have escalated the price of treatment.

Ronald C. Chen, MD, MPH, of the department of radiation oncology at University of North Carolina Hospitals in Chapel Hill, and colleagues sought to determine the comparative morbidity of disease control of IMRT, proton therapy and conformal radiation therapy for primary prostate cancer treatment.

The researchers analyzed Surveillance, Epidemiology, and End Results (SEER)-Medicare data and focused on 15,963 men who underwent radiation treatment within one year of a prostate cancer diagnosis between 2000 and 2007.

The primary outcomes were gastrointestinal morbidity, urinary incontinence, nonincontinence urinary morbidity, sexual dysfunction and hip fractures. Chen and colleagues used receipt of additional cancer therapy after radiation therapy as an indicator of disease recurrence.

IMRT vs. conformal therapy utilization increased from 0.15 percent in 2000 to 95.9 percent in 2008.

Men who underwent IMRT were less likely to be diagnosed with gastrointestinal morbidity than those treated with conformal therapy, at 13.4 vs. 14.7 per 100-person years, respectively. Patients in the IMRT cohort also were less likely to be diagnosed with a hip fracture. IMRT-treated patients were less likely than conformal therapy-treated patients to undergo additional cancer therapy at 2.5 per 100 person-years for IMRT vs. 3.1 for conformal therapy.

Chen and colleagues offered two explanations for the reduced likelihood of gastrointestinal morbidity and hip fracture in the IMRT-treated cohort. IMRT may enable physicians to deliver minimized doses to the bowel and femoral head. However, “another possibility is an improvement in physician understanding of and attention to organ dose guidelines, which may have paralleled the adoption of IMRT, resulting in better treatment plans that may have also been achievable with conformal radiation therapy.”

Erectile dysfunction diagnosis was more likely in the IMRT group, at 5.9 per 100 person-years, vs. 5.3 in the conformal group. That may be because researchers have not yet determined the relevant anatomic structures associated with radiation-induced erectile dysfunction.

The researchers did not find significant differences between proton therapy and IMRT-treated patients in urinary nonincontinence or incontinence diagnoses or procedures, erectile dysfunction or procedures or hip fractures. However, patients treated with proton therapy were more likely to be diagnosed with gastrointestinal morbidity and undergo gastrointestinal procedures. Chen and colleagues suggested that proton therapy is more vulnerable to organ movement, which may lead to an unintentional higher dose to the rectum compared with IMRT.

They concluded, “Overall, our results do not clearly demonstrate a clinical benefit to support the recent increase in proton therapy use for prostate cancer… With the recent rapid increases in the number of proton facilities, comparative data are needed.”

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