Consequences of different definitions of disease progression in observational studies of men with advanced prostate...

Definitions of prostate specific antigen progression for men with prostate cancer on androgen deprivation therapy (ADT) are mainly derived from randomised trials, and their applicability to the clinical practice remains uncertain. This study aimed to assess how different PSA-based definitions of progressions while on ADT affect estimates of progression, treatment initiation, and outcomes in men with prostate cancer.

Using data from the Prostate Cancer database of Sweden with extended treatments and endpoints data (PCBase Xtend), we identified 3718 men who initiated ADT between 2009 and 2022 and who had longitudinal PSA and treatment data. PSA progression was defined according to four modified guideline-based definitions ranging from the European Association of Urology (EAU) that has the most stringent criteria for progression to our previously used and less stringent definition (PCBase). We analysed cumulative incidence of PSA progression, treatment for castration resistant prostate cancer before and after PSA progression, and prostate cancer-specific mortality, accounting for competing risks.

ADT was prescribed as the primary treatment in 52% of included men. The number of men with PSA progression ranged by definition from 1047 men (28%, EAU) to 2378 men (64%, PCBase) at 10 years after initiation of ADT. Earlier progression was observed with less stringent criteria, with a difference in median time to progression of 3 months (PCBase vs EAU). Despite variation in incidence proportion of PSA progression, the proportion of men treated within 5 years after progression was similar (45-52%), as was prostate cancer-specific mortality (26-27%) across definitions.

While definitions of PSA progression significantly impacted estimated incidence proportion of disease progression, they had limited influence on treatment initiation and long-term mortality. These findings suggest that in the clinical practice, decisions are guided by factors other than formal progression criteria. PSA-based definitions can be useful in observational studies if supported by sensitivity analyses.