This randomised trial included men from 47 centres in Norway, Sweden, and Denmark. Between February, 1996, and December, 2002, 875 patients with locally advanced prostate cancer (T3; 78 % ; PSA<70; N0; M0) were centrally randomly assigned by computer to endocrine treatment alone (3 months of total androgen blockade followed by continuous endocrine treatment using flutamide; 439 patients), or to the same endocrine treatment combined with radiotherapy (436 patients). The primary endpoint was prostate-cancer-specific survival, and analysis was by intention to treat. This study is registered as an international standard randomised controlled trial, number ISRCTN01534787.
After a median follow-up of 7·6 years, 79 men in the endocrine alone group and 37 men in the endocrine plus radiotherapy group had died of prostate cancer. The cumulative incidence at 10 years for prostate-cancer-specific mortality was 23·9 % in the endocrine alone group and 11·9 % in the endocrine plus radiotherapy group (difference 12·0 % , 95 % CI 4·9–19·1 % ), for a relative risk of 0·44 (0·30–0·66). At 10 years, the cumulative incidence for overall mortality was 39·4 % in the endocrine alone group and 29·6 % in the endocrine plus radiotherapy group (difference 9·8 % , 0·8–18·8 % ), for a relative risk of 0·68 (0·52–0·89). Cumulative incidence at 10 years for PSA recurrence was substantially higher in men in the endocrine-alone group (74·7 % vs 25·9 % , p<0·0001; HR 0·16; 0·12–0·20). After 5 years, urinary, rectal, and sexual problems were slightly more frequent in the endocrine plus radiotherapy group.
In patients with locally advanced or high-risk local prostate cancer, addition of local radiotherapy to endocrine treatment halved the 10-year prostate-cancer-specific mortality, and substantially decreased overall mortality with fully acceptable risk of side-effects compared with endocrine treatment alone. In the light of these data, endocrine treatment plus radiotherapy should be the new standard.
Schering-Plough, Abbott Scandinavia, Nordic Cancer Union, Swedish Cancer Society (070604), Norwegian Cancer Society, Lions Cancer Foundation, and Umeå University.