Higher-dose radiation therapy does not raise toxicity in prostate cancer

Boston-Increasing the radiation dose for better local control of prostate cancer does not increase long-term toxicity, according to data from a randomized clinical trial.

This study, reported at the American Society of Clinical Oncology annual meeting in Chicago, also revealed substantial deviation between clinically assessed symptoms and patient-reported symptoms, suggesting that adaptation over time changes patient perception of symptoms and their impact on quality of life.

The findings came from an American College of Radiology-sponsored trial involving 393 men with localized prostate cancer treated with a combination of photon and proton radiation. This trial was designed to examine the benefits and risks of a total radiation dose of 79.2 Gy compared to a conventional 70.2-Gy dose.

In the initial study, the higher dose significantly improved biochemical relapse-free survival after 5.5 years of follow-up: 81.4% for the 79.2-Gy cohort compared with 61.4% for the 70.2-Gy group (p<.001), as reported in JAMA (2005; 294:1233-9). Physician-assessed morbidity demonstrated no significant differences between the treatment arms. However, some concern about long-term treatment-related morbidity persisted because of the recognized insensitivity of physician-assessed versus patient-reported adverse effects.

To assess the long-term treatment effects, investigators contacted the original study participants to determine their perception of symptoms 8 years or longer after completion of treatment. Dr. Talcott reported data on 248 patients who had returned questionnaires.

The primary finding was that the two treatment groups did not differ significantly with respect to any of the symptoms assessed. Using a scale of 0 to 100 to rate severity of symptoms after radiation therapy, patients in the 79.2-Gy group ranked their urinary incontinence, urinary obstruction or irritation, bowel problems and sexual dysfunction at 10.1, 24.3, 7.7, and 67.9 on average, compared with averages of 10.9, 23.2, 7.5, and 67.7, respectively, for the 70.2-Gy group. Overall, average symptom scores were 10.5, 23.7, 7.6, and 67.8, respectively. Dr. Talcott suggested two possible explanations for the lack of additional morbidity with the higher radiation dose.

"Part of it may be that patients don't see [an adverse effect] as a symptom; they see it as the new 'normal'," he said. "Also, it could be that use of proton radiation might have a mitigating effect on treatment-related toxicity."

Comparison of clinically assessed symptoms and patient-reported symptoms supported the concept that an adaptive process may occur over time. For example, among patients rated as having normal bowel function, all but one agreed that they had normal function. However, 80% of patients with intermediate bowel symptoms also rated their bowel function as normal, as did 40% of patients with clinically rated poor bowel function. Almost 50% of patients with poor bowel function considered their problems intermediate in severity.