The addition of external beam therapy to brachytherapy did not significantly extend PFS among men with intermediate-risk prostate cancer, according to the initial report of a phase 3 study presented at the ASTRO Annual Meeting.
Thus, radiation treatment with brachytherapy alone may provide adequate cancer control for this population, resulting in fewer long-term adverse events, results showed.
“Low-risk prostate cancer can be treated by either surgery, external beam therapy or brachytherapy, equally successfully. In fact, in recent years many investigators and doctors in clinical practice have elected to do active surveillance on patients and hold off on treatment completely until the patient progresses,” Bradley Prestidge, MD, medical director of the Bon Secours Cancer Institute at DePaul Medical Center in Norfolk, Virginia, said during a press conference. “But, patients with intermediate-risk prostate cancer have conventionally received external beam therapy alone or sometimes with hormone therapy, or in combination with brachytherapy, but traditionally not brachytherapy alone.”
Prestidge and colleagues hypothesized that patients with intermediate-risk prostate cancer who received external beam therapy in addition to brachytherapy — or the insertion of radioactive seed implants into a patient’s tissue to limit radiation exposure to surrounding, healthy tissue — would have a 10% improvement in 5-year PFS compared with patients who received brachytherapy alone.
The analysis included data from 579 men (median age, 67 years) with intermediate-risk prostate cancer. Patients had clinical stage T1c (67%) to T2b disease and a Gleason score between 2 and 6 with a PSA between 10 and 20, or a Gleason score of 7 and a PSA less than 10 (89%).
Researchers randomly assigned patients to receive brachytherapy alone (n = 292) or with 45 Gy partial external beam therapy to the pelvic area (n = 287). Brachytherapy used radioactive Iodine-125 or Palladium-103 in 110- or 100-Gy doses for patients who also received external beam therapy, and 146-Gy or 125-Gy doses for patients who received that treatment alone.
PFS served as the study’s primary endpoint. The incidence of short-term acute and long-term late side effects also served as an outcome measure.
Median follow-up was 6.7 years.
Researchers were able to evaluate data from 443 patients at 5-year follow-up.
Sixty-six patients experienced a first failure, 34 of whom were in the combination arm and 32 of whom received brachytherapy alone.
Overall, rates of 5-year PFS were 85% (95% CI, 80-89) among men who underwent external beam therapy plus brachytherapy, and 86% (95% CI, 81-90) among men who received brachytherapy alone (HR = 1.02; P for futility = .0006). Based on these results, the data monitoring committee recommended early release of the findings.
The rates of acute grade 2 or worse toxicity (28% vs. 27%) and acute grade 3 or worse toxicity (8% for both) were comparable in the combination and brachytherapy arms. However, more patients in the combination arm experienced late grade 2 or worse toxicity (53% vs. 37%; P = .0001) and late grade 3 or worse toxicity (12% vs. 7%; P = .039). More patients in the combination arm experienced grade 3 or worse genitourinary toxicity (7% vs. 3%), but rates of grade 3 or worse gastrointestinal toxicity were comparable (3% vs. 2%).
“This means men with intermediate-risk prostate cancer may be quite well managed with brachytherapy alone,” Prestidge said. “That represents a bit of a paradigm shift compared with when the study was originated. It is going to require further analysis to look at subsets, such as more favorable vs. less favorable intermediate risk, to see if heterogeneity in the groups leads to any differences between the two. And, of course, longer follow-up will be even more meaningful.”– by Alexandra Todak
Prestidge BR, et al. Abstract 7. Presented at: ASTRO Annual Meeting; Sept. 25-28, 2016; Boston.
Disclosure: The researchers report no relevant financial disclosures.