Androgen suppression combined with external irradiation improves survival in high metastatic risk prostate cancer patients

Professor Michel Bolla and coworkers have reported the final results of the EORTC 22863 trial, Phase III Randomized Comparison of Pelvic Radiotherapy Alone versus Pelvic Radiotherapy plus the LHRH Analogue Goserelin and Cyproterone Acetate in Carcinoma of the Prostate at High Risk for Metastasis, in the November issue of The Lancet Oncology [1]. Their ten year results show that for high metastatic risk prostate cancer patients, treatment with a luteinizing hormone releasing hormone (LHRH) agonist in addition to external irradiation improves 10-year disease free survival (DFS) and overall survival (OS) without increasing late cardiovascular toxicity.

As compared to treatment with radiotherapy and deferred androgen deprivation at time of relapse, combined use of long term androgen suppression and external beam irradiation has been shown to improve OS in high metastatic risk prostate cancer patients. Previously, Bolla and coworkers showed that six months of androgen suppression followed by androgen suppression in case of relapse was inferior to three years of immediate androgen suppression for patients with locally advanced prostate cancer [2]. There was concern, however, that long term androgen suppression might lead to an increased risk of fatal myocardial infarction and bone fractures. The ten year results of the EORTC 22863 trial confirm that previously reported improvements in OS are sustained, and no significant difference in cardiovascular mortality was noted between the two treatment groups. (Two fractures were reported in patients who had received long term androgen suppression in addition to radiotherapy.)

The first patient entered this trial in May 1987, and accrual was completed in October 1995; the preliminary results were published in the New England Journal of Medicine [3]. Results at 5.5 years median follow up were published in The Lancet and showed major improvement for DFS and OS with the long term androgen deprivation treatment [4].

This long term analysis with 10 year median follow up included all 415 patients who were randomly assigned to receive radiotherapy alone (208 patients) or immediate androgen suppression in addition to radiotherapy, i.e., the combined treatment (207 patients). Ten year DFS was 22.7% (95% CI 16.3 – 29.7) in patients who received radiotherapy alone, and 47.7% (39.0 – 56.0) in patients who received the combined treatment (hazard ratio [HR] 0.42, 95% CI 0.33 – 0.55, p<0.0001). Ten year OS was 39.8% for the radiotherapy alone group (95% CI 31.9 – 47.5) and 58.1% for the combined group (49.2 – 66.0) (HR 0.60, 95% CI 0.45 – 0.80, p=0.0004); ten year prostate cancer mortality was 30.4% (95% CI 23.2 – 37.5) and 10.3% (5.1 – 15.4), for the radiotherapy alone and combined treatment groups, respectively (HR 0.38, 95% CI 0.24 – 0.60, p<0.0001).

From a public health point of view, such a combined treatment has become a reference in daily practice.

John Bean
EORTC, Medical Science Writer

[1] M. Bolla, G. Van Tienhoven, P. Warde, J.B. Dubois, R.O. Mirimanoff , G. Storme, J. Bernier, A. Kuten, C. Sternberg, I. Billiet, J. Lopez Torecilla, R. Pfeffer, C.L. Cutajar, T. Van der Kwast, L. Collette. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. The Lancet Oncol 11: 1066-1073, 2010.

[2] M. Bolla, T.M. de Reijke, G. Van Tienhoven, Van den Bergh ACM, Oddens J, Poortmans PMP, Gez E, Kil P, Akdas A, Soete G, Kariakine O, van der Steen-Banasik EM, Musat E, Pierat M, Mauer M, and Collette L. Duration of Androgen Suppression in the Treatment of Prostate cancer. N Engl J Med 360:2516-27, 2009.

[3] M. Bolla, D. Gonzalez, P. Warde, J.B. Dubois, R.O. Mirimanoff, G. Storme, J. Bernier, A. Kuten, C. Sternberg, T. Gil, L. Collette, M. Pierart. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserilin. N Engl J Med 337:295-300, 1997.

[4] Bolla M, L. Collette, L. Blank, P. Warde, J.B. Dubois, R.O. Mirimanoff, G. Storme, J. Bernier, A. Kuten, C. Sternberg, J. Mattelaer, J.L. Torecilla, J.R. Pfeffer, C.L. Cutajar, M. Pierart. Long term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomized trial. Lancet 360: 103-8, 2002.