Survival and PSA-markers for mortality and metastasis in nonmetastatic prostate cancer treated with androgen deprivation therapy.

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.

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.

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 <8ng/mL, PSA ≥8ng/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.

PSA ≥8ng/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.

Cancer epidemiology. 2015 Jun 19 [Epub]

Mary Nguyen-Nielsen, Alexander Liede, Merete Lund Maegbaek, Michael Borre, Niels Harving, Rohini Khorana Hernandez, Henrik Toft Sørensen, Vera Ehrenstein

Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark.  Center for Observational Research, Amgen, Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark. Department of Urology, Aarhus University Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N, Denmark. Department of Urology, Aalborg University Hospital, Reberbansgade 15, 9100 Aalborg, Denmark. Center for Observational Research, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA.  Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark. 

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