Men with clinically localized prostate cancer (PCa) treated with high-dose radiation do not experience more long-term toxicities than those treated with standard-dose radiation, according to a recent study.

A team led by James A. Talcott, MD, of the Center for Outcomes Research in Charlestown, Mass., which is part of Massachusetts General Hospital in Boston, studied 280 surviving participants in the Proton Radiation Oncology Group (PROG) 9509, a randomized trial comparing standard-dose (70.2 Gy) and high-dose (79.2 Gy) radiation treatment for clinically localized PCa.

The high-dose therapy was a combination of x-ray and proton radiation. Proton therapy decreases the radiation delivered to non-targeted adjacent tissue compared with x-ray radiation, although the radiation target volume contains some normal tissue. 

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Previously, PROG 9509 showed that patients receiving high-dose radiation had a significantly improved 10-year estimated biochemical recurrence rate compared with the standard-dose group (17% vs. 32%).

For the new study, researchers gave subjects self-administered questionnaires that included the four prostate cancer symptom indices (PCSI) to assess urinary incontinence, urinary obstruction and irritation, bowel problems, and sexual dysfunction. At the time of survey completion, participants had a median age of 76 years. Each PCSI scale item was scored on a scale of 0 (no reported symptoms) to 100 (maximum possible dysfunction).

At a median of 9.4 years after treatment, patients in both groups showed no significant differences in mean scale scores for all toxicity categories, 
Dr. Talcott’s group reported in the Journal of the American Medical Association (2010;303:1046-1053). The mean scores for the standard- and high-dose groups were 10.6 and 9.7, respectively, for urinary incontinence, 23.3 and 24.6 for urinary obstruction and irritation, 7.7 and 7.9 for bowel problems, and 68.2 and 65.9 for sexual dysfunction. 

Patients in the standard-dose group, who had a greater likelihood of biochemical progression, were significantly less confident that their prostate cancer was under control.

“While these results need to be confirmed,” said Dr. Talcott, Associate Professor of Medicine at Harvard Medical School in Boston, “it’s looking as if we should tell patients that treatment side effects probably will bother them less than they originally fear because they are likely to adjust and experience less distress over time. We may also need to rethink our standard measures of treatment outcomes, which assume that the impact of symptoms on patients’ quality of life does not change over time.”

The investigators offered potential explanations for their findings. One possibility, they noted in their report, is that an efficacious increased radiation dose does not increase long-term toxicity to adjacent normal tissues if given using techniques (such as proton beam) that minimize dose to nearby critical tissues.

“In this sense, our results may be taken as validating this technology and confirm the similar physician-reported short- and long-term toxicity for standard-dose and high-dose patients initially reported,” they wrote.

Another possibility is that patients treated with high-dose radiation may have experienced increased toxicity earlier in their course that resolved during the approximately 10 years of follow-up. With regard to sexual dysfunction, the investigators pointed out that this increases progressively in the age group of men included in the study whether or not they have had radiation treatment. Thus, “it may not be possible to detect a further increment [in sexual dysfunction] due to the extra radiation dose against the increasing background dysfunction.” 

Additionally, it may be that men who had high-dose treatment did experience greater treatment-related toxicity “but have adapted to their condition over time and no longer notice or report it.” Moreover, “highly motivated men may be more satisfied with the outcome of a technologically novel therapy that, in many cases, they actively researched and sought. Proton beam is undoubtedly one such therapy,” the authors noted. n