The impact of time to metastasis on overall survival in patients with prostate cancer

Time to metastasis is often used as a surrogate parameter of treatment success in clinical trials for prostate cancer. However, it has not been shown that there is a clear correlation between time to metastasis and overall survival. Our objective was to evaluate the impact of time to metastasis on OS in patients with prostate cancer. Between 2008 and 2015, 269 patients with mPCa were included in this retrospective study with a median follow-up of 7.1 years. Patients were divided into three groups: (1) Presentation with metastasis within three months of initial diagnosis (de-novo-M); (2) patients free of metastasis initially but developed metastasis more than 6 months prior to castration resistance (CSPC-M); (3) patients who developed metastasis within 6 months of becoming castration resistant or after (CRPC-M). There was a significant decrease in OS when metastases were present at diagnosis (median 6.39 years) compared to CRPC-M (19.07) and CSPC-M (18.19 years). De-novo-M and CSPC-M showed a longer OS from occurrence of metastasis to death when compared to CRPC-M, although reaching CRPC earlier. There was no difference in OS between the groups once castration resistance was reached. Time from initial diagnosis to metastasis and to CRPC was correlated with OS and remained important prognosticators in multivariate Cox-regression (p < 0.01 for both). Time from diagnosis to CRPC (all patients) and time to metastasis (for CRPC-M and CSPC-M patients) are significant prognosticators of overall survival and are therefore valid surrogates in a study setting. Therefore, time to CRPC should be prolonged as long as possible.