Prevalence and Natural History of Non-metastatic Castrate Resistant Prostate Cancer: A Population-Based Analysis

To determine the prevalence and natural history of nmCRPC prior to the adoption of novel androgen receptor axis-targeting therapies(ARAT). This was a retrospective population-based cohort study of men with nmCRPC in Ontario, Canada between January 2007-March 2018. Patients with prostate cancer, castrate level of testosterone(2.0ng/mL with a subsequent rise>25% from the nadir, and without metastasis were included. Annual prevalence of nmCRPC was calculated. Crude time from nmCRPC to metastasis and all-cause death are presented as medians with interquartile range(IQR). Predictors of time from nmCRPC to death were compared using univariable and multivariable cox proportional hazard models. We identified 2045 patients with nmCRPC. Median age was 79(IQR:72-84). 984 patients(48.1%) received upfront hormonal therapy while 583(28.5%) received initial radiotherapy and 478(23.4%) underwent radical prostatectomy. Median time from primary treatment to nmCRPC was 6 years(IQR:3-10). The average annual prevalence of nmCRPC was 8% among men receiving ADT. Crude median time from nmCRPC to death was 37.6 months(IQR:22.1-55.4). Median time from nmCRPC to metastasis and metastasis to death was 20.0 and 8.3 months, respectively. Patients who had primary surgery experienced longer crude survival. Older patients, patients who had a higher PSA at nmCRPC, and patients with grade group 4 to 5 disease had a shorter time from nmCRPC to death. This is the largest population-level analysis of the prevalence and natural history of nmCRPC. The current study can be used as a historical cohort to compare how novel imaging modalities and ARAT impact prevalence and disease trajectory over time. We found that 8% of all men with prostate cancer on androgen deprivation therapy have castrate resistant disease without evidence of metastasis. One in 5 of these men experienced spread of the cancer within 3 years. Older patients, patients with a higher PSA, and patients with aggressive cancer at the time of initial diagnosis were at higher risk of death.