Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial
Anders Widmark, Olbjørn Klepp, Arne Solberg, Jan-Erik Damber, Anders Angelsen, Per Fransson, Jo-Asmund Lund, Ilker Tasdemir, Morten Hoyer, Fredrik Wiklund, Sophie D Fosså, Scandinavian Prostate Cancer Group Study 7, Swedish Association for Urological Oncology 3, Peter Iversen, Per-Age Højsaeter, Sten Nilsson, Harald Anderson, Lars Holmberg, Olav Dahl, Ingela Turesson, Per Lundmo, Morten Hoyer, Finn Lundback, Lena Damber, B J Norlen, K M Kalkner, S Ljungerud, S Bratell, S Puterman, T Lindbeborg, G Ljung, T Sandin, S Bergström, B Asklin, R Lundgren, S Süsskind, B Kiehl, S A Lindahl, P O Hedlund, P Wersäll, J Löfqvist, S Karlsson, S Collén, P Flodgren, L Bohman, S Hellsten, C E Lindholm, B Hahne, R Ideström, S O Andersson, B Ernström, C Bergh, M Waldén, T Sandin, A Kristoffersson, A Owczarski, B Lennernäs, R Olsson, R Tomic, A Widmark, A Ramsing, A Ullman, L Bohman, A Victorin, S Haukaas, O Maehlum, L Daehlin, D C Johannesen, H Waere, S D Fosså, W Lilleby, S Vaage, C Ginman, J Due, T Norøy, A Angelsen, P Lundmo, O Klepp, A Solberg, B Hahne, J Thorvik, D T Nordli, G Waaler, R H Hagen, P Holme, H O Nefoss Kirurgisk Avd, M Bech, A Gustavsen, H Steen, K Vada, P C Medbye, O Modalsli, I Høye, T Johannesen, T Urnes, R Kalsnes, Anders Widmark, Olbjørn Klepp, Arne Solberg, Jan-Erik Damber, Anders Angelsen, Per Fransson, Jo-Asmund Lund, Ilker Tasdemir, Morten Hoyer, Fredrik Wiklund, Sophie D Fosså, Scandinavian Prostate Cancer Group Study 7, Swedish Association for Urological Oncology 3, Peter Iversen, Per-Age Højsaeter, Sten Nilsson, Harald Anderson, Lars Holmberg, Olav Dahl, Ingela Turesson, Per Lundmo, Morten Hoyer, Finn Lundback, Lena Damber, B J Norlen, K M Kalkner, S Ljungerud, S Bratell, S Puterman, T Lindbeborg, G Ljung, T Sandin, S Bergström, B Asklin, R Lundgren, S Süsskind, B Kiehl, S A Lindahl, P O Hedlund, P Wersäll, J Löfqvist, S Karlsson, S Collén, P Flodgren, L Bohman, S Hellsten, C E Lindholm, B Hahne, R Ideström, S O Andersson, B Ernström, C Bergh, M Waldén, T Sandin, A Kristoffersson, A Owczarski, B Lennernäs, R Olsson, R Tomic, A Widmark, A Ramsing, A Ullman, L Bohman, A Victorin, S Haukaas, O Maehlum, L Daehlin, D C Johannesen, H Waere, S D Fosså, W Lilleby, S Vaage, C Ginman, J Due, T Norøy, A Angelsen, P Lundmo, O Klepp, A Solberg, B Hahne, J Thorvik, D T Nordli, G Waaler, R H Hagen, P Holme, H O Nefoss Kirurgisk Avd, M Bech, A Gustavsen, H Steen, K Vada, P C Medbye, O Modalsli, I Høye, T Johannesen, T Urnes, R Kalsnes
Abstract
Background: Several studies have shown the efficacy of endocrine therapy in combination with radiotherapy in high-risk prostate cancer. To assess the effect of radiotherapy, we did an open phase III study comparing endocrine therapy with and without local radiotherapy, followed by castration on progression.
Methods: 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.
Findings: 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.
Interpretation: 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.
Source: PubMed