Mary Nguyen-Nielsen1, Alexander Liede2, Merete Lund Maegbaek3, Michael Borre4, Niels Harving5, Rohini Khorana Hernandez6, Henrik Toft Sørensen7, Vera Ehrenstein8. 1. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark. Electronic address: maryniel@rm.dk. 2. Center for Observational Research, Amgen, Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. Electronic address: aliede@amgen.com. 3. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark. Electronic address: mlm@econ.au.dk. 4. Department of Urology, Aarhus University Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N, Denmark. Electronic address: borre@clin.au.dk. 5. Department of Urology, Aalborg University Hospital, Reberbansgade 15, 9100 Aalborg, Denmark. Electronic address: niha@rn.dk. 6. Center for Observational Research, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: rohinih@amgen.com. 7. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark. Electronic address: hts@clin.au.dk. 8. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark. Electronic address: ve@clin.au.dk.
Abstract
BACKGROUND: Few studies have examined the risk of developing castration-resistant prostate cancer (CRPC), metastasis, and mortality among nonmetastatic prostate cancer (M0-PC) patients treated with androgen deprivation therapy (ADT). We estimated the incidence of these outcomes among M0-PC patients on ADT and identified prostate-specific antigen (PSA) based biomarkers for mortality and metastasis. METHODS: This population-based cohort study included all nonmetastatic prostate cancer patients in Northern and Central Denmark Regions during 1997-2010, identified through registry data. Primary outcomes were metastasis, overall survival, and bone metastasis-free survival (BMFS). We estimated relative risks (RR) associated with PSA and PSA doubling-time (PSA-DT), measured as time-varying variables beginning at ADT treatment start. RESULTS: We included 2494 M0-PC patients treated with ADT, of whom 1617 (80%) developed CRPC during follow-up. One-fourth of the patients developed metastases within 5 years; bone metastases (BM) accounted for 81% of all metastases. Median survival time was 4.4 years. Compared with PSA <8 ng/mL, PSA ≥8 ng/mL was associated with an adjusted RR of 14.0 (95% confidence interval [CI]: 10.2, 19.0) for BM, 4.4 (CI: 3.9, 5.0) for all-cause mortality, and RR of 4.8 (CI: 4.3, 5.4) for the inverse of BMFS. PSA-DT ≤6 months was associated with an adjusted RR of 7.6 (95% CI: 6.1, 9.5) for BM, RR of 5.9 (CI: 5.2, 6.6) for all-cause mortality, and RR 6.6 (CI: 5.9, 7.4) for the inverse of BMFS. CONCLUSIONS: PSA ≥8 ng/mL and PSA-DT ≤6 months are strong predictors of mortality and bone metastasis. The poor prognosis observed in this study may reflect inclusion of patients with severe prostate cancer by requiring repeated PSA measurements.
BACKGROUND: Few studies have examined the risk of developing castration-resistant prostate cancer (CRPC), metastasis, and mortality among nonmetastatic prostate cancer (M0-PC) patients treated with androgen deprivation therapy (ADT). We estimated the incidence of these outcomes among M0-PC patients on ADT and identified prostate-specific antigen (PSA) based biomarkers for mortality and metastasis. METHODS: This population-based cohort study included all nonmetastatic prostate cancerpatients in Northern and Central Denmark Regions during 1997-2010, identified through registry data. Primary outcomes were metastasis, overall survival, and bone metastasis-free survival (BMFS). We estimated relative risks (RR) associated with PSA and PSA doubling-time (PSA-DT), measured as time-varying variables beginning at ADT treatment start. RESULTS: We included 2494 M0-PC patients treated with ADT, of whom 1617 (80%) developed CRPC during follow-up. One-fourth of the patients developed metastases within 5 years; bone metastases (BM) accounted for 81% of all metastases. Median survival time was 4.4 years. Compared with PSA <8 ng/mL, PSA ≥8 ng/mL was associated with an adjusted RR of 14.0 (95% confidence interval [CI]: 10.2, 19.0) for BM, 4.4 (CI: 3.9, 5.0) for all-cause mortality, and RR of 4.8 (CI: 4.3, 5.4) for the inverse of BMFS. PSA-DT ≤6 months was associated with an adjusted RR of 7.6 (95% CI: 6.1, 9.5) for BM, RR of 5.9 (CI: 5.2, 6.6) for all-cause mortality, and RR 6.6 (CI: 5.9, 7.4) for the inverse of BMFS. CONCLUSIONS:PSA ≥8 ng/mL and PSA-DT ≤6 months are strong predictors of mortality and bone metastasis. The poor prognosis observed in this study may reflect inclusion of patients with severe prostate cancer by requiring repeated PSA measurements.
Authors: Yashar Khoshkar; Marcus Westerberg; Jan Adolfsson; Anna Bill-Axelson; Henrik Olsson; Martin Eklund; Olof Akre; Hans Garmo; Markus Aly Journal: BJUI Compass Date: 2021-10-10
Authors: Eugenio Ventimiglia; Anna Bill-Axelson; Jan Adolfsson; Markus Aly; Martin Eklund; Marcus Westerberg; Pär Stattin; Hans Garmo Journal: Eur Urol Open Sci Date: 2022-08-23