Risk of prostate cancer death after radical radiotherapy with neoadjuvant and adjuvant therapy with bicalutamide or gonadotropin-releasing hormone agonists

Abstract

Background

Oncological outcome after radical radiotherapy (RRT) combined with neoadjuvant and adjuvant androgen suppression therapy (AST) may differ according to type of AST. The aim of this nationwide register-based study was to investigate risk of prostate cancer (Pca) death after different neoadjuvant and adjuvant ASTs; (i) bicalutamide, (ii) gonadotropin-releasing hormone agonists (GnRH) or (iii) combined bicalutamide and GnRH (CAB), together with RRT.

Materials and Methods

Data for 6882 men diagnosed with high-risk Pca between 2007 and 2020 and treated with primary RRT was retrieved from Prostate Cancer data Base Sweden (PCBaSe) 5.0. Time to Pca death according to type of neoadjuvant and adjuvant AST was assessed by use of Kaplan–Meier plots and Cox proportional hazard models adjusted for putative confounders.

Results

Data were stratified by RRT type since the effect of AST in risk of Pca death differed according to type of RRT. Compared with the reference RRT combined with neoadjuvant CAB/adjuvant GnRH, risk of Pca death for men treated with CAB/bicalutamide and conventionally fractionated external beam radiotherapy (CF-EBRT) was hazard ratio (HR) 0.73 (95% CI: 0.50–1.04), hypofractionated EBRT (HF-EBRT), HR 1.35 (95% CI: 0.65–2.81) and EBRT with high dose rate brachytherapy (EBRT-HDRBT), HR 0.85 (95% CI: 0.37–1.95). Risk of Pca death for men treated with bicalutamide/bicalutamide and: (i) CF-EBRT was HR 2.35 (95% CI: 1.42–3.90), (ii) HF-EBRT, HR 0.70 (95% CI: 0.26–1.85), (iii) HF-EBRT, HR 4.07 (95% CI: 1.88–8.77) vs the reference.

Conclusion

In this observational study, risk of Pca death between men receiving different combinations of AST varied according to RRT type. No difference was found in risk of Pca death for men treated with bicalutamide or GnRH as adjuvant therapy to RRT following neoadjuvant CAB. Risk of Pca death was increased for men with monotherapy neo-/adjuvant bicalutamide in combination with CF-EBRT or EBRT-HDRBT.

Keywords:

• Prostate neoplasms
• androgen antagonists
• gonadotropin-releasing hormone
• radiotherapy
• prognosis
• mortality

Acknowledgements

This project was made possible by the continuous work of the National Prostate Cancer Register of Sweden (NPCR) steering group: Ingela Franck Lissbrant (chairman), Johan Styrke, David Robinson, Johan Stranne, Jon Kindblom, Camilla Thellenberg, Andreas Josefsson, Ingrida Verbiené, Hampus Nugin, Stefan Carlsson, Anna Kristiansen, Karin Holmsten, Mats Andén, Thomas Jiborn, Olof Akre, Per Fransson, Eva Johansson, Johan Stranne, Magnus Törnblom, Fredrik Jäderling, Marie Hjälm Eriksson, Lotta Renström Koskela, Jonas Hugosson, Ola Bratt, Erik Thimansson, Elin Trädgårdh, Viktoria Gaspar, MariaNyberg, Fredrik Sandin, Marie Brus, Gustaf Hedström Anna Hedström, Nina Hageman, Christofer Lagerros, Hans Joelsson, and Gert Malmberg.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The participants of this study did not give written consent for their data to be shared publicly, so due to the sensitive nature of the research supporting data is not available. The data are not publicly available due to restrictions, for example, their containing information that could compromise the privacy of research participants.

Additional information

Funding

This project received research support from the Clinical Cancer Research Foundation in Jönköping, Sweden and from FUTURUM - Academy for Healthcare, Jönköping County, Sweden.