Overdiagnosis for screen-detected prostate cancer incorporating patient comorbidities

Abstract Background Evidence regarding the likelihood of overdiagnosis in prostate cancer (CaP) screening with PSA are mainly based on clinical trials, which include younger population with fewer comorbidities than those receiving the test in clinical practice. We aimed to assess the likelihood of overdiagnosis and associated variables using real-world data. Methods Retrospective cohort of men >40 years with PCa, who had been diagnosed being asymptomatic and after a positive PSA test in the previous 12 months in two hospitals (2004-2022). The probability of overdiagnosis was estimated considering the life expectancy of the Spanish male in the year 2022 and the Charlson Comorbidity Index (lead time 10 years). PSA values and Gleason score were included as independent variables. Results Of the 2,331 patients in the cohort, 1,070 (46%) met the inclusion criteria for this analysis. The median follow-up time was 5.7 years (IQR 3.2-8.6). The median age was 71 years (IQR 65-78) and 37% had more than one comorbidity. At diagnosis, the median life expectancy was 12 years (IQR 4-18) and the probability of overdiagnosis was 30.8% (IQR 17.6-52.4). Patients with PSA levels >10 mg/dl tended to be older and with more comorbidities than those with PSA levels 4-10 mg/dl, and thus, with shorter life expectancy. The median probability of overdiagnosis was higher in patients with PSA levels >10 mg/dl (41.4%, IQR 21.5-73.9) than in those with PSA levels 4-10 mg/dl (20.1%, IQR 12.8-30.4), p < 0.001. Correspondingly, patients with Gleason score ≥8 were more likely to be overdiagnosed (median 42.6%, IQR 23.6-68.6) than those with Gleason score ≤6 (median 20.1%, IQR 12.8-30.4) (p < 0.001). Conclusions In clinical practice, older patients with comorbidities showed high PSA levels and Gleason score ≥8, presenting low life expectancy at diagnosis and, therefore, high probability of overdiagnosis. This highlights the importance of considering the patient’s comorbidities when ordering a new PSA test. Key messages • A detailed assessment of the prevalence of comorbidities among CaP patients in real-life settings has significant implications for patient management. • The decision to make an early diagnosis should be based on individual life expectancy, where comorbidity is at least as important as age.