Estimating scenarios for survival time in men starting systemic therapies for castration-resistant prostate cancer: a systematic review of randomised trials.
BACKGROUND
We sought to estimate worst-case, typical and best-case scenarios for survival in men starting systemic therapies for castration resistant prostate cancer (CRPC).


METHODS
We sought randomised phase 3 trials of systemic therapies for CRPC and recorded the following percentiles (represented scenario) from Kaplan-Meier overall survival (OS) curves: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical) and 10th (best-case). We determined the accuracy of using simple multiples of the median OS to estimate the other selected percentiles from each curve: 0.25 for 90th, 0.5 for 75th, 2 for 25th and 3 for 10th. Estimates were deemed accurate if within 0.75-1.33 times the actual value.


RESULTS
We reviewed 23 trials (13,909 men) with 48 treatment groups including 28 of chemotherapy, and three of novel hormonal agents. In trials of first-line docetaxel, the mean (interquartile range) for median OS was 19 months (17-20), and for each scenario was: worst-case 7 months (6-8); lower-typical 12 months (11-13); upper-typical 29 months (27-31); and best-case 40 months (34-44). For trials of novel hormonal agents after chemotherapy the mean values were: median OS 17 months, worst-case 5 months, lower-typical 9 months, upper-typical 24 months and best-case not reported. Simple multiples of the median gave accurate estimates of the worst-case scenario in 72% of OS curves, lower-typical in 89%, upper-typical in 84% and best-case in 84%.


CONCLUSIONS
Simple multiples of the median OS from randomised trials provided accurate estimates of worst-case, typical and best-case scenarios for survival time in men starting systemic therapies for CRPC.
Sydney Medical School, University of Sydney, Edward Ford Building A27, NSW 2006, Australia.
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West
National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown, NSW 1450, Australia; Department of Medical Oncology, Sydney Cancer Centre, RPA and Concord Hospitals, Missenden Road, Camperdown, NSW 2050, Australia.
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Kiely
Sydney Medical School, University of Sydney, Edward Ford Building A27, NSW 2006, Australia; National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Locked Bag 77, Camperdown, NSW 1450, Australia; Department of Medical Oncology, Sydney Cancer Centre, RPA and Concord Hospitals, Missenden Road, Camperdown, NSW 2050, Australia. Electronic address: martin.stockler@sydney.edu.au.
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Stockler
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal
Chemotherapy; Prognosis; Prostate cancer; Survival time