Ten Year Results of Long Term Adjuvant Androgen Deprivation with Goserelin in Patients with Locally Advanced Prostate Cancer Treated with Radiotherapy: A Phase III EORTC Study

To demonstrate that the significant increase in overall survival of patients with locally advanced prostate cancer obtained adding long term androgen deprivation (LTAD) to external irradiation (RT) (N Engl J Med 1997; Lancet 2001) is maintained in the long term without increasing cardiovascular and bone toxicity. From 1987 to 1995, 415 patients with locally advanced prostate cancer under age 81 were randomly allocated to combined RT plus LTAD or RT alone, followed by the same hormonal therapy in case of relapse. Eligible patients had T1T2 WHO grade 3 M0 or T3-4 N0-1 M0 tumors. The whole pelvis was irradiated with photons ≥10 MV up to 50 Gy delivered over 5 weeks, followed by a boost of 20 Gy in 10 fractions to the prostate and seminal vesicles. LTAD was given by a monthly injection of Zoladex 3.6 mg (goserelin), started the first day of irradiation, continued for a period of 3 years. Statistical analysis is by intention-to-treat at the 2-sided 5% significance level. Clinical, pathological, biological characteristics were well balanced in the two cohorts; the median age was 71 years. At a median follow-up of 9.1 years, 192 of 415 patients have died (112 on RT alone and 80 on RT plus LTAD). The addition of LTAD to RT increased the 10-year overall survival from 39.8% to 58.1% (HR = 0.60, CI: 0.45-0.80, p = 0.0004), clinical progression free survival (PFS) from 22.7% to 47.7% (HR = 0.42, CI: 0.33-0.55, p < 0.0001), distant PFS from 30.2% to 51.0 % (HR = 0.50, CI: 0.38-0.65, p < 0.0001), and clinical or biochemical PFS from 17.6% to 37.9% (HR = 0.43, CI: 0.30-0.60, p < 0.0001). The 10-year cumulative incidence of prostate cancer mortality was 31.0% on RT and 11.1% on RT plus LTAD (HR = 0.38, CI: 0.24-0.60, p < 0.001). The 10-year cumulative incidence of cardiovascular mortality amounts respectively to 11.1% and 8.2% (HR = 1.11, CI: 0.59-2.09, p = 0.75). Two pathological fractures were reported in the combined treatment arm which occurred respectively 7.2 years and 9.9 years after entry. LTAD (3 years) combined with external irradiation improves overall survival as compared to RT alone. In patients with locally advanced prostate cancer without apparently increasing late cardiovascular toxicity.