AIM: Evidence supporting radiotherapy for prostate cancer 'insufficient'

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A U.S. government-sponsored review of trials comparing radiotherapy with no treatment or other forms of radiotherapy has concluded that there is insufficient evidence that patients with localized prostate cancer will benefit from radiation therapy, according to a study published online June 6 in the Annals of Internal Medicine.

Prostate cancer remains the most common non-skin cancer among U.S. men, resulting in roughly 192,000 diagnoses and 27,000 deaths in 2009. In 2008, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review of treatment options, which concluded that therapies varied both in effectiveness and adverse effects.

The present study was an updated meta-analysis, commissioned by AHRQ and the Centers for Medicare & Medicaid Services (CMS) and completed by researchers at the Institute of Clinical Research and Health Policy Studies at Tufts University School of Medicine in Boston. Overall, 75 studies comparing the effects of radiotherapies against one another and against no treatment were included in the review, including 10 randomized, controlled trials and 65 nonrandomized comparative studies.

Only studies in which 80 percent or more of participants had localized prostate cancer were included. The strength of all studies was evaluated as high, moderate or insufficient.

The authors concluded that the evidence of benefit of radiotherapy to localized prostate cancer survival was insufficient. Nearly all cross-treatment comparisons of dose and radiotherapy method were likewise deemed insufficient.

“This updated review showed unclear effectiveness of radiation treatments compared with no treatment or no initial treatment of localized prostate cancer on patient survival,” explained Raveendhara R. Bannuru, MD, and co-authors from Tufts University School of Medicine. “Similarly, evidence was insufficient to determine whether certain forms of radiation treatment were more effective than others."

No randomized, controlled trials directly evaluated radiotherapy against no treatment. One of four retrospective studies found a statistically significant improvement among patients treated with brachytherapy versus those monitored but not initially treated with radiotherapy.

Three retrospective studies comparing radiotherapy with no therapy indicated that treatment impaired bowel or urinary function. Another study found a significantly higher rate of secondary cancers among patients treated with external-beam radiation therapy (EBRT) than among those who did not undergo radiation.

Based on 14 studies (including three randomized, controlled trials), Bannuru and colleagues concluded that moderate evidence suggested that higher doses of EBRT were associated with increased long-term biochemical control compared with lower EBRT doses. No significant differences in urinary or bowel toxicities were observed between the two dose ranges.

The authors also considered that brachytherapy may yield higher rates of urinary toxicity than EBRT.

“[C]urrently available evidence is insufficient to draw definitive conclusions about the effectiveness of radiation treatments for localized prostate cancer compared with no treatment or no initial treatment. Despite the addition of new studies, these conclusions remain largely similar to those from the 2008 review,” wrote Bannuru et al.

The authors considered discrepancies in the design and measured outcomes of studies as making a summary of the evidence “challenging.” Individually tailored treatments, variations in disease stages and the administration of androgen deprivation therapy (ADT) likewise confounded the authors’ results.

Bannuru and co-authors put some future stock in two ongoing trials (one in Canada, the other in the UK) comparing radiation therapy and other treatments with active surveillance.