Concomitant and adjuvant androgen deprivation (ADT) with external beam irradiation (RT) for locally advanced prostate cancer: 6 months versus 3 years ADT—Results of the randomized EORTC Phase III trial 22961

Abstract

5014 Background: After EORTC trial 22863, 3 years of endocrine treatment has become standard adjuvant treatment to RT for locally advanced prostate cancer. EORTC 22961 tests if similar survival can be achieved in patients who underwent EBRT (to 70 Gy) and 6 months of combined ADT without further ADT (SADT arm) as in patients with 2.5 years of further treatment with luteinizing hormone-releasing hormone agonist monotherapy (LADT arm). Methods: Eligible patients had T1c-2b N1–2 or pN1–2, or T2c-4 N0–2 (UICC 1992) M0 prostate cancer with PSA <150ng/ml. Non-inferior survival was defined as a morality hazard ratio (HR) = 1.35 for SADT vs LADT. Non inferiority at 80% power and 1-sided a=0.05 required 275 deaths. A stopping boundary was applied at 1-sided a=0.018. Results: 970 patients were randomized (483 SADT and 487 LADT). At 5.2 years median follow-up, 173 patients had died (100 vs 73). An Independent Data Monitoring Committee recommended disclosure of results based on an interim analysis showing futility. Patient characteristics were well balanced: median age 69 years, WHO PS 0 in 83.4%, most patients had T2c-T3 N0 disease. Progression (mostly biochemical and/or bone progression) occurred in 220 cases (159 on SADT vs 61 on LADT) and was treated by secondary hormonal manipulation. The 5-year overall survival rate was 85.3% on LADT and 80.6% on SADT (HR=1.43, 96.4% CI: 1.04–1.98), and failed to prove non-inferiority. The 5-year clinical progression-free survival rate was 81.8% on LADT versus 68.9% on SADT arm and the 5-year biochemical progression-free survival rate was 78.3% on LADT versus 58.9% on SADT, indicating inferiority of SADT with HR=1.93 and HR=2.29, respectively. Conclusions: The study was designed to demonstrate non-inferior survival with 6 months ADT compared to 3 years adjuvant ADT after irradiation for patients with locally advanced prostate cancer, but observed survival data indicate that non-inferiority cannot be confirmed. Progression-free survival was also shorter on SADT. No significant financial relationships to disclose.

Does hormone treatment added to radiotherapy improve outcome in locally advanced prostate cancer?

“…One paper reported the results of 2 trials8; 1 was excluded because it was designed to compare HT duration without an exclusive RT arm. Three additional RCTs were excluded for the same reason 23‐25. Seven and 5 RCTs, respectively, were evaluable for biochemical failure (3956 patients, data lacking for 179 patients) and clinical progression‐free survival (4020 patients, data lacking for 2 RCTs8, 13).…”

Expanded risk groups help determine which prostate radiotherapy sub-group may benefit from adjuvant androgen deprivation therapy

“…Another possible explanation could be that the ADT duration for the high and extreme risk groups was insufficient. Prolonging the duration of ADT appears to benefit patients with a higher chance of relapse following EBRT [ 18 , 19 ]. A previous analysis from our institution also demonstrated an advantage to prolonged, rather than shorter ADT duration (6 months versus 12 versus 24 months) in patients with localized disease and a PSA above 20 [ 20 ].…”

10-Year Survival and Quality of Life in Patients With High-Risk PN0 Prostate Cancer Following Definitive Radiotherapy

“…The optimal duration of HT is unclear. Two randomized trials have shown that, compared with six months of HT together with conventional radiotherapy 70Gy, 28 months(137) or 36 months(138) improves PCa-specific outcomes. Results from another study suggest that treatment for more than six years may benefit some patients(139).D'Amico et al showed recently that even though radiotherapy + six months of HT improved overall survival compared with radiotherapy alone for localized unfavorable-risk PCa, this was not true for a subgroup of patients with moderate to severe comorbidity.…”