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The time from joining a trial until a scan first shows the cancer has spread, or the man dies, whichever comes first. It is the endpoint that got three hormone drugs licensed for prostate cancer that had not yet spread, because waiting for deaths would have taken another decade.
Metastasis-free survival is a composite time-to-event endpoint: the interval from randomisation to the first radiographic evidence of distant metastasis or death from any cause, whichever occurs first. Its rise in prostate cancer solved a specific problem. In non-metastatic castration-resistant disease and in high-risk localised disease, overall survival takes ten to fifteen years to read out, by which time the control arm has received several treatments that did not exist when the trial opened. PCWG3 recommended time to first metastasis and time to progression as outcome measures for trials in the non-metastatic castration-resistant state for exactly this reason.
The surrogacy evidence is the ICECaP meta-analysis. Xie, Regan and colleagues collected individual patient data from 28 randomised trials in localised prostate cancer covering 28,905 patients, with metastasis-free survival evaluable in 12,712 patients from 19 trials after a median 10 years of follow-up. At the patient level Kendall's tau correlation with overall survival was 0.91; at the trial level, the correlation of treatment effects measured as log hazard ratios was R squared 0.92 (95 percent confidence interval 0.81 to 0.95), against 0.73 for disease-free survival. That is a strong surrogate by the two-stage meta-analytic standard, and it is the reason regulators accepted the endpoint.
The definition differs between trials, which is the part that matters when two numbers are compared. It is set by each protocol, not by a single standards body, and the three things that vary are the imaging used, who reads it and what counts as an event. SPARTAN defined metastasis-free survival as the time from randomisation to the first detection of distant metastasis on imaging or death, in men with non-metastatic castration-resistant disease and a prostate-specific antigen doubling time of 10 months or less, with conventional imaging (technetium bone scan and computed tomography) read by blinded independent central review; median metastasis-free survival was 40.5 months with apalutamide against 16.2 months with placebo (hazard ratio 0.28; 95 percent confidence interval 0.23 to 0.35). Conventional imaging is doing the work in all of these trials. PSMA PET finds metastatic disease that a bone scan cannot see, so a man classified as non-metastatic in 2018 would often be classified as metastatic in 2026, and the ninth edition of TNM now asks that such a finding be recorded as M1(PET). Metastasis-free survival figures measured on bone scan and on PSMA PET are not the same quantity and should not be pooled.
Showing the technology this term belongs to: PSMA PET.
The current shape of the screening question in the United States, and the best short statement of the trade-off in numbers a man can weigh. The three-to-one ratio between metastatic cases prevented and deaths prevented is also the argument for using metastatic presentation, not mortality, to judge a screening programme sooner.
The trial that made an androgen receptor inhibitor the usual first treatment for castration-resistant prostate cancer, and that delayed chemotherapy by a long margin for most men. Its effect sizes are why later trials in this setting are judged against a hazard ratio near 0.7 for survival.
Shares USPSTF 2018: screening for prostate cancer, recommendation statement (grade C at 55 to 69, grade D at 70 and over), Judge a prostate screening programme on metastatic presentation, not on incidence or mortality, Hazard ratio (HR), Localised prostate cancer, high and very high risk and the tags gu, prostate-glossary.
Shares USPSTF 2018: screening for prostate cancer, recommendation statement (grade C at 55 to 69, grade D at 70 and over), Non-metastatic castration-resistant prostate cancer, Hazard ratio (HR), Metastatic hormone-sensitive prostate cancer and the tags gu, prostate-glossary.
Shares Biochemical recurrence of prostate cancer, Hazard ratio (HR), Metastatic hormone-sensitive prostate cancer, Localised prostate cancer, high and very high risk and the tags gu, prostate-glossary.
Shares USPSTF 2018: screening for prostate cancer, recommendation statement (grade C at 55 to 69, grade D at 70 and over), Judge a prostate screening programme on metastatic presentation, not on incidence or mortality, The hardest cancers are found late, Prostate cancer and the tags gu, prostate-glossary.
Shares Judge a prostate screening programme on metastatic presentation, not on incidence or mortality, The hardest cancers are found late, Trial design, endpoints and cost, Prostate cancer and the tags gu, prostate-glossary.
Shares Randomise the order of treatment, not only the drugs: a strategy platform for metastatic prostate cancer, Castration-resistant prostate cancer (CRPC), Trial design, endpoints and cost, Prostate cancer and the tags gu, prostate-glossary.
Shares Localised prostate cancer, high and very high risk, The hardest cancers are found late, Prostate cancer and the tags gu, prostate-glossary.
Shares Localised prostate cancer, high and very high risk, The hardest cancers are found late, Prostate cancer and the tags gu, prostate-glossary.