Introduction: The natural history of non-metastatic castrate resistant prostate cancer (nmCRPC) prior to the introduction of novel anti-androgen agents in a real-world setting is largely unknown. Our primary aim was to determine the prevalence and natural history of nmCRPC.
Methods: This was a retrospective population-based cohort study of men with nmCRPC in Ontario, Canada. Patients with a diagnosis of prostate cancer, castrate level of testosterone ( <1.7nmol/L) and a PSA >2.0nmol/L with a subsequent rise >25% from the nadir, and without diagnostic or treatment codes for metastasis were included. Annual prevalence of nmCRPC was calculated. Crude time from nmCRPC to metastasis and death are presented as medians with interquartile range (IQR). Predictors of time from nmCRPC to prostate cancer death were compared using univariable and multivariable Fine and Gray subdistributional hazard models to account for the competing risk of non-prostate cancer death.
Results: From January 2007 until March 2018, we identified 2045 patients with nmCRPC. Median age was 79 years (IQR: 72-84). A total of 984 patients (48.1%) received upfront hormonal therapy while 584 (25.8%) received initial radiotherapy (RT) and 478 (23.4%) previously underwent radical prostatectomy. Median time from primary treatment to nmCRPC was 6 years (IQR: 3-10). PSA at the time of meeting nmCRPC criteria was a median of 3.0 ng/L. Patients were followed for a median 31.1 months (IQR: 19.8-47.9). The overall annual prevalence of nmCRPC ranged from 1,519-1,913 patients, representing 7-12% of men with prostate cancer prescribed androgen deprivation therapy each year. Crude median time from nmCRPC to all-cause death was 37.6 months (IQR: 22.1-55.4). Median time from nmCRPC to metastasis and metastasis to all-cause death was 20.0 and 8.3 months, respectively. On regression analysis, older patients, patients who had a higher PSA at the time of meeting nmCRPC criteria, and patients with grade group 4-5 disease had a shorter time from nmCRPC to prostate cancer death.
Conclusions: This is the largest 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 advancements in systemic therapy for patients with nmCRPC impact prevalence estimates and disease trajectory over time.
Source of Funding: This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and Ministry of Long-Term Care (MLTC) (grant number not applicable). This study also received funding from the Ajmera Family Chair in Urologic Oncology awarded to RKN (grant number not applicable). We thank IQVIA Solutions Canada Inc. for use of their Drug Information File.
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