As reported in the Journal of Clinical Oncology by Bolla et al, a 12-year analysis among patients with localized intermediate-risk prostate cancer in the EORTC 22991 trial showed improved event-free and disease-free survival with the addition of 6 months of concomitant and adjuvant androgen suppression to external-beam radiotherapy (EBRT) at 74 or 78 Gy.
As stated by the investigators, “[The trial] showed that 6 months of concomitant and adjuvant androgen suppression improves event-[free] and clinical disease–free survival of intermediate- and high-risk localized prostatic carcinoma, treated by EBRT at 70 to 78 Gy. We report the long-term results in intermediate-risk patients treated with 74 or 78 Gy EBRT, as per current guidelines.”
Study Details
Among 819 patients in the trial randomly assigned to receive EBRT or EBRT plus androgen suppression started on day 1 of EBRT, 481 had intermediate-risk disease and had EBRT planned at 74 Gy (n = 342) or 78 Gy (n = 139). Among the 481 patients, 245 were randomly assigned to EBRT plus androgen suppression (173 at 74 Gy, 72 at 78 Gy) and 236 to EBRT only (169 at 74 Gy, 67 at 78 Gy). The primary endpoint was event-free survival.
Six months of concomitant and adjuvant androgen suppression statistically significantly improves event-free survival and disease-free survival in intermediate-risk prostatic carcinoma, treated by irradiation at 74 or 78 Gy.— Bolla et al
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Key Findings
At a median follow-up of 12.2 years, 92 of 245 patients in the EBRT plus androgen-suppression group vs 132 of 236 in the EBRT group had event-free survival events, most commonly prostate-specific antigen relapse (48.7%) or death (45.1%). Event-free survival at 10 years was 68.1% (95% confidence interval [CI] = 61.6%–73.7%) in the EBRT plus androgen-suppression group vs 49.3% (95% CI = 42.4%–55.8%) in the EBRT group (hazard ratio [HR] = 0.53, 95% CI = 0.41–0.70, P < .001). Results did not differ according to EBRT dose (HRs of 0.54 for 74 Gy and 0.52 for 78 Gy, P = .874 for interaction).
Disease-free survival at 10 years was 76.2% vs 66.0% (HR = 0.67, 95% CI = 0.49–0.90, P = .008; P for interaction of P = .571 for the two EBRT doses). The difference primarily reflected lower incidence of locoregional relapse in the EBRT plus androgen-suppression group; at 10 years, cumulative locoregional relapse occurred in 4.4% vs 9.6% (competing risk-adjusted HR = 0.44, 95% CI = 0.23–0.84, P = .013).
Distant metastases developed in 14 (5.7%) vs 20 (8.5%) of patients, with 10-year distant metastasis–free survival rates of 79.3% vs 72.7% (HR = 0.74, 95% CI = 0.53–1.02, P = .065). Death occurred in 64 (26.1%) vs 76 (32.2%) of patients, with 10-year overall survival rates of 80.0% vs 74.3% (HR = 0.74, 95% CI = 0.53–1.04, P = .082). As stated by the investigators, the lack of significance in the two outcomes was not unexpected, given the relatively small numbers of events (150 and 140, respectively, and that the trial was not powered to detect difference in these endpoints).
Late toxicities included grade ≥ 3 genitourinary toxicity in 7.4% vs 4.3% of patients (P = .174), severe impairment in sexual function in 30.9% vs 22.1% (P = .038), and grade ≥ 3 gastrointestinal toxicity in 1.3% vs 1.3%.
The investigators concluded, “Six months of concomitant and adjuvant androgen suppression statistically significantly improves event-free survival and disease-free survival in intermediate-risk prostatic carcinoma, treated by irradiation at 74 or 78 Gy. The effects on overall survival and distant metastasis–free survival did not reach statistical significance.”
Michel Bolla, MD, of the Department of Radiation Oncology, Grenoble University Hospital, France, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Ligue Nationale contre le Cancer (France), Kom op tegen Kanker (Stand up to Cancer), the Flemish cancer society (Belgium), and AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.
