Anti-androgen monotherapy versus gonadotropin-releasing hormone agonists in men with advanced, non-metastatic prostate cancer: a register-based, observational study

Abstract

Background: In randomised controlled trials, men with advanced, non-metastatic prostate cancer (PCa) treated with anti-androgen monotherapy (AA) had similar all-cause mortality as men treated with gonadotropin-releasing hormone (GnRH) agonists. Using real-world evidence (i.e., observational data), we aimed to further assess the difference in mortality between these two drug categories.

Material and Methods: We emulated a trial using data from Prostate Cancer data Base Sweden 3.0. We specifically focused on men diagnosed in 2006–2012 with high-risk PCa who had no distant metastasis. They either received primary hormonal therapy with AA (n = 2078) or GnRH agonists (n = 4878) who were followed for a median time of 5 years. Risk of death from PCa and other causes was assessed using competing risk analyses and Cox proportional hazards regression analyses, including propensity score matching.

Results: The cumulative 5-year PCa mortality was lower for men treated with AA (16% [95% confidence interval, CI, 15–18%]) than men treated with GnRH agonists (22% [95% CI 21–24%]). The 5-year other cause mortality was also lower for men on AA (17% [95% CI 15–19%] compared to men on GnRH agonists (27% [95% CI 25–28%]). In regression analyses, the risk of PCa death was similar, GnRH agonists versus AA (reference), hazard ratio (HR) 1.08 (95% CI 0.95–1.23), but the risk of death from all causes was higher for men on GnRH agonists, HR 1.23 (95% CI 1.13–1.34). Consistent results were seen in the propensity score-matched cohort.

Conclusion: Our results indicate that the use of AA as primary hormonal therapy in men with high-risk non-metastatic PCa does not increase PCa-specific mortality compared to GnRH. Using AA instead of GnRH agonists may result in shorter time on/exposure to GnRH-treatment, which may reduce the risk of adverse events associated with this treatment.

Acknowledgments

This project was made possible by the continuous work of the National Prostate Cancer Register of Sweden (NPCR) steering group: Pär Stattin (chairman), Anders Widmark, Camilla Thellenberg Karlsson, Ove Andrén, Ann-Sofi Fransson, Magnus Törnblom, Stefan Carlsson, Marie Hjälm-Eriksson, David Robinson, Mats Andén, Jonas Hugosson, Ingela Franck Lissbrant, Maria Nyberg, Ola Bratt, Lars Egevad, Calle Waller, Stig Hanno, Olof Akre, Per Fransson, Eva Johansson, Fredrik Sandin, and Karin Hellström.

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported by The Swedish Research Council 825-2012-5047 and The Swedish Cancer Society 16 0700. FBT is supported by research grant from IMK Almene fond. The sponsors had no involvement with the planning, execution or completion of the study.