by Charles Bankhead

There is still not enough evidence to show that radiation therapy for localized prostate cancer is better than surveillance, according to a report prepared for the Centers for Medicare and Medicaid Services (CMS).

Only retrospective analyses have compared irradiation with no treatment or no initial treatment. Data comparing the relative efficacy of different types of radiation therapy also are insufficient to permit definitive conclusions regarding efficacy, safety, and toxicity, according to the report from investigators at Tufts University in Boston.

“Definitive benefits of radiation treatments compared to no treatment or no initial treatment for localized prostate cancer could not be determined because available data were insufficient to make this determination,” Stanley Ip, MD, and co-authors wrote.

“Many of the findings reported in this review were inconsistent for each of the outcomes of interest,” they said in the report. “The studies reviewed showed substantial heterogeneity.”

Many of the deficiencies in the data stem from clinical trials’ attempt to provide individualized or tailored therapy to each patient.

“This makes it difficult, if not impossible, to assess the comparative efficacies between two forms of radiation treatments,” the authors wrote.

How CMS plans to use the report remains unclear. A spokesperson told MedPage Today that the report is for “informational purposes only.” No additional discussions or actions have been announced, he said.

The findings are consistent with those of a 2007 review conducted by a research group in Minnesota. Authors of the earlier report concluded that “limitations in the body of evidence” and patient-related factors hampered attempts to determine the relative risks and benefits of different types of radiation therapy.

The Tufts researchers were tasked with three questions:

* What are the benefits and harms of radiation therapy for clinically localized prostate cancer compared with no treatment or no initial treatment in terms of clinical outcomes?
* What are the benefits and harms of different forms of radiation therapy for clinically localized prostate cancer?
* How do specific patient characteristics affect the outcomes of thee different forms of radiation therapy?

The search for answers picked up where the Minnesota study left off. Ip and colleagues conducted a literature review to identify relevant studies published January 2007 through December 2009. They included randomized and nonrandomized comparative clinical studies and excluded single-cohort studies; evaluations of adjuvant, salvage, or postprostatectomy radiation therapy; and studies of androgen deprivation therapy.

The review encompassed two broad categories of radiation therapy: external beam radiation therapy (including intensity-modulated radiotherapy, conformational radiation, stereotactic body radiation, and proton beam) and brachytherapy (permanent seed implantation and high-dose temporary brachytherapy). The investigators also included studies of combinations of radiation therapy.

Comparators of interest were no treatment or no initial treatment and alternate forms of radiation therapy. Principal outcomes examined were overall and prostate cancer-specific survival, metastatic- and progression-free survival, freedom from biochemical (PSA) failure, quality of life, bowel and urinary toxicities, and sexual dysfunction. The investigators limited the analysis to reported outcomes for T1 or T2 disease.

The review yielded about 1,300 citations, which reviewers culled down to 62 relevant studies. From those studies, Ip and colleagues concluded that comparisons of different types of external-beam radiation therapy had yielded moderate-strength evidence with regard to freedom from biochemical failure and genitourinary/gastrointestinal toxicity. They defined moderate evidence as two or more B-quality studies that yielded similar results.

For all other comparisons, including observation or active surveillance, the authors found the evidence insufficient to judge the effects on outcomes of interest and definitively answer the three questions.

Any evaluation of the report should recognize distinctions between what the Tufts researchers did not say, as well as what they did, commented Anthony Zietman, MD, Massachusetts General Hospital and Harvard, who did not participate in the study.

“They’ve concluded not that radiation therapy is ineffective, because there is plenty of evidence that radiation eradicates prostate cancer, or that radiation does not have any side effects, because everyone knows that it does,” said Zietman, who is a clinical spokesperson for the American Society of Radiation Oncology.

“As I see it, they have concluded that there is no comparative effect. It is really tough to say whether one kind of radiation is any better than any other kind of radiation.

“Beyond that, the question they didn’t seem to address was whether radiation is better, the same, or worse than surgery. All of the treatments for prostate cancer suffer from the same problem. They’ve really only been compared with themselves. What CMS and Medicare want to see is comparative effectiveness data, and it doesn’t exist right now.”

Charles Bankhead is a MedPage Today staff writer.

Originally published in MedPage Today. Visit MedPageToday.com for more prostate cancer news.