Professor University of Michigan, VA Ann Arbor Healthcare System
Introduction: Prostate cancer recurrence after surgery often presents as asymptomatic, biochemically recurrent, non-metastatic castration-sensitive disease. The extent to which the use and timing of ADT in this setting is associated with progression to metastatic disease is largely unknown. For these reasons, we conducted a population-based study to examine associations between biochemical recurrence management and progression along the castration cascade. Methods: We used national electronic health record, cancer registry, administrative, pharmacy, and laboratory data to conduct a retrospective cohort study of men undergoing radical prostatectomy for localized prostate cancer from 2005 through 2015 in the Veterans Health Administration. We followed men through 2019 for biochemical recurrence, defined as PSA =0.2 ng/mL, and incident metastatic disease, identified using a validated natural language processing algorithm. We used multivariable regression to examine associations between metastatic disease and patient, disease, and salvage management approaches including ADT. Results: We identified 8,558 men with biochemical recurrence after radical prostatectomy. Most patients were managed with observation and/or salvage radiation therapy (70%). Metastatic disease occurred in 14% and on univariate analysis was associated with decreased time to biochemical recurrence (15.5 months, metastatic vs. 19.2 months non-metastatic), younger age at recurrence, positive surgical margins, higher pathologic stage and PSA at diagnosis (all p<0.01). Salvage ADT was used in 30% of patients with recurrence, mostly among men who remained non-metastatic (65%). Pre-ADT PSA was higher among men with metastatic disease (4.1 ng/mL metastatic vs. 0.9 ng/mL non-metastatic, p<0.001), as was castration-resistant drug use (48.2% metastatic vs. 4.5% non-metastatic, p<0.001). Salvage ADT was highly associated with metastatic disease in this observational study (adjusted odds ratio 6.04, 95% CI 4.68-7.81). Conclusions: Management of biochemically recurrent disease after radical prostatectomy varied widely, including the use and timing of ADT. We found metastatic disease occurred in about 1 in 7 men with recurrence and was associated with traditional risk factors. While most salvage ADT was for non-metastatic disease, the extent to which castration use in observational data reflects disease severity or incites castration-resistance and metastatic disease warrants further study. SOURCE OF Funding: NCI R01 CA242559
