Results of EORTC 22991: 3D-CRT/IMRT with or without 6-month androgen deprivation therapy in localized T1b-cT2aN0M0 prostate cancer (EORTC 22991)

Bolla M.1, Maingon P.2, Van Den Bergh A.3, Carrie C.4, Villa S.5, Kitsios P.6, Poortmans P.7, Sundar S.8, Van Der Steen-Banasik E.9, Collette L.10

1Centre Hospitalier Universitaire De Grenoble-La-Tronche, Dept. of Radiotherapy, Grenoble, 2Centre Georges-Francois-Leclerc, Dept. of Radiotherapy, Dijon, 3University Medical Center Groningen, Dept. of Radiotherapy, Groningen, 4Centre Leon Berard, Dept. of Radiotherapy, Lyon, 5Hospital Universitari Germans Trías, Institut Català D’Oncologia, Dept. of Radiotherapy, Badalona, 6Bank of Cyprus Oncology Centre, Dept. of Radiotherapy, Nicosia, 7Dr. Bernard Verbeeten Instituut, Dept. of Radiotherapy, Tilburg, 8Nottingham University Hospitals NHS Trust - City Hospital, Dept. of Radiotherapy, Nottingham, 9Arnhem's Radiotherapeutisch Instituut, Dept. of Radiotherapy, Arnhem, 10European Organisation For Research and Treatment of Cancer Headquarters, Dept. of Statistics, Brussels

Introduction & Objectives

After primary irradiation, up to 30% patients with intermediate or high risk localized prostate cancer relapse biochemically within 5 years. This study evaluates the combination of 6 months of medical castration with primary irradiation.

Material & Methods

819 patients staged cT1b-c with PSA ≥ 10ng/ml or Gleason ≥7 or cT2a (UICC TNM 1997) N0 M0 with PSA≤ 50 ng/ml were randomized 1:1 between irradiation (RT) or irradiation and 2 injections of LH-RH analogue (gosereline acetate) with 1 month of anti-androgens. Randomization was performed centrally. Centers opted for one prostate irradiation dose among 70Gy, 74 Gy or 78 Gy. Irradiation of pelvic nodes for patients who have at least 15% risk was left to the discretion of each institution.
Biochemical progression-free survival (BPFS primary endpoint) was counted from entry until PSA relapse (Phoenix criteria) or until clinical relapse (evidenced by imaging) or death of any cause if they occur without PSA relapse. The trial aimed for 80% power of detecting HR=0.714 by intention-to-treat analysis at the 2-sided 5% significance level with stratification for RT dose, which required 274 events. (ClinicalTrials.gov NCT00021450).

Results

Median patient age was 70y, 88% were WHO PS0, 74.8% classified intermediate risk and 24.8% high risk by D’Amico classification. In the RT arm, 407/409 received RT, in the RT+HT, 403/410 received RT+HT and 3 RT only. Six patients refused treatment. After a median follow-up of 7.2 years, based on 319 events of BPFS (201 with RT vs 118 with RT+HT), BPFS was statistically significantly improved with RT+HT (HR=0.53, CI: 0.42-0.67, P<0.001) at all radiation doses (heterogeneity P>0.1) with an increase at 5 years from 69.3% to 82.5%. Clinical progression-free survival was also statistically significantly improved (205 events, HR=0.63, CI: 0.48-0.84, P=0.001, +7.9% at 5 years). Only 152 patients died so far of which 25 died of prostate cancer. Late genito-urinary toxicity was reported by 5.9% vs 3.6% of the patients, on RT+HT and RT, respectively (P=0.14), whereas 27.0% vs 19.4% reported severe impairment of sexual function (P=0.010).

Conclusions

The addition of 6 months of medical castration to primary irradiation improves biochemical and clinical progression-free survival in intermediate and high risk localized T1b-cT2a N0M0 prostatic carcinoma.