Impact of Time to Castration Resistance on Survival in Metastatic Hormone Sensitive Prostate Cancer Patients in the Era of Combination Therapies

Mike Wenzel; Felix Preisser; Benedikt Hoeh; Maria Schroeder; Christoph Würnschimmel; Thomas Steuber; Hans Heinzer; Severine Banek; Marit Ahrens; Andreas Becker; Pierre I Karakiewicz; Felix K H Chun; Luis A Kluth; Philipp Mandel

doi:10.3389/fonc.2021.659135

Impact of Time to Castration Resistance on Survival in Metastatic Hormone Sensitive Prostate Cancer Patients in the Era of Combination Therapies

Front Oncol. 2021 Apr 23:11:659135. doi: 10.3389/fonc.2021.659135. eCollection 2021.

Authors

Affiliations

¹ Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany.
² Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, QC, Canada.
³ Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
⁴ Department of Hematology and Oncology, University Hospital Frankfurt, Frankfurt, Germany.

Abstract

Background: To evaluate the impact of time to castration resistance (TTCR) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies for mHSPC.

Material and methods: Of 213 mHSPC patients diagnosed between 01/2013-12/2020 who subsequently developed metastatic castration resistant prostate cancer (mCRPC), 204 eligible patients were analyzed after having applied exclusion criteria. mHSPC patients were classified into TTCR <12, 12-18, 18-24, and >24 months and analyzed regarding OS. Moreover, further OS analyses were performed after having developed mCRPC status according to TTCR. Logistic regression models predicted the value of TTCR on OS.

Results: Median follow-up was 34 months. Among 204 mHSPC patients, 41.2% harbored TTCR <12 months, 18.1% for 12-18 months, 15.2% for 18-24 months, and 25.5% for >24 months. Median age was 67 years and median PSA at prostate cancer diagnosis was 61 ng/ml. No differences in patient characteristics were observed (all p>0.05). According to OS, TTCR <12 months patients had the worst OS, followed by TTCR 12-18 months, 18-24 months, and >24 months, in that order (p<0.001). After multivariable adjustment, a 4.07-, 3.31-, and 6.40-fold higher mortality was observed for TTCR 18-24 months, 12-18 months, and <12 months patients, relative to TTCR >24 months (all p<0.05). Conversely, OS after development of mCRPC was not influenced by TTCR stratification (all p>0.05).

Conclusion: Patients with TTCR <12 months are at the highest OS disadvantage in mHSPC. This OS disadvantage persisted even after multivariable adjustment. Interestingly, TTCR stratified analyses did not influence OS in mCRPC patients.

Keywords: CRPC; castration resistance; metastatic prostate cancer; mortality; survival.