Androgen deprivation therapy (ADT) can be safely reduced from 36 months to 18 months in high-risk prostate cancer, according to final results of a randomized phase III trial. However, the statistical design of the study may prevent firm conclusions on the best duration of treatment.
Abdenour Nabid, MD, of Centre Hospitalier Régional Universitaire in Sherbrooke, Quebec, presented results (abstract 5008) of the PCS IV trial at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago. The trial included 630 patients randomized to 36 months (310 patients) or 18 months (320 patients) of ADT (bicalutamide plus goserelin); all patients received radiation therapy, and the median follow-up in the study was 9.4 years.
Patients all had high-risk disease, and were well matched between the groups, with a median age of 71 years. The median prostate-specific antigen (PSA) level in the 36-month patients was 16.4 ng/mL, and in the 18-month patients it was 15.4 ng/mL; the median Gleason score was 8 in both groups. In the full cohort, 24.1% had T3–T4 disease, 44.3% had a PSA level above 20 ng/mL, and 59.7% had a Gleason score above 7.
The overall survival (OS) was similar between the two groups. At 5 years, the 36-month patients had an OS rate of 90.9%, and the 18-month patients had an OS rate of 86.1%. At 10 years, these rates were 62.4% and 62.0%, respectively. The hazard ratio (HR) for OS was 1.024 (95% CI, 0.813–1.289; P = .8411); a multivariate analysis confirmed this, with an HR of 1.01 (95% CI, 0.80–1.27; P = .9431).
A quality of life analysis favored the 18-month ADT duration. This was clinically significant and covered multiple aspects.
Disease-specific survival was also similar. At 10 years, the HR was 0.948 (95% CI, 0.582–1.546; P = .830). Biochemical failure at 10 years was more likely in the 18-month group, at 31.0% compared with 24.8%, for an HR in favor of the longer duration of 0.714 (95% CI, 0.532–0.952; P = .024). Disease-free survival was similar, with an HR of 0.835 (95% CI, 0.683–1.020; P = .0768).
“In localized high-risk prostate cancer treated with radiation therapy and ADT, ADT duration can be safely reduced from 36 to 18 months,” Nabid concluded, adding that 18 months could represent a threshold effect beyond which little extra benefit is derived. “Eighteen months of ADT represents a new standard of care.”
That conclusion, though, may be somewhat premature. Susan Halabi, PhD, of Duke University Medical Center in Durham, North Carolina, was the discussant for the session, and she pointed out that a non-significant test result from a superiority comparison cannot be used to establish similarity between the treatments. “The optimal duration of ADT for high-risk localized prostate cancer is not known, and remains a clinically important question.”