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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-04-01
• Series: Frontiers in Oncology
• Subjects: mortality; survival; castration resistance; metastatic prostate cancer; CRPC
• Online Access: https://www.frontiersin.org/articles/10.3389/fonc.2021.659135/full

BackgroundTo 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 MethodsOf 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.ResultsMedian 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).ConclusionPatients 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.