Abstract
Simple SummaryIn this study, we used a well calibrated risk prediction model to define prostate-specific antigen (PSA) thresholds for identifying or excluding advanced prostate cancer (PCa) as an aid to personalize management of the diagnostic workup. PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa in patients without glandular inflammation, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) suggested a biopsy referral. In the presence of glandular inflammation, PSA does not provide a valid estimate for risk of advanced cancer since the marker variability is higher and the pre-test probability of PCa is low in this group. The proposed PSA thresholds may allow an individualized approach to the diagnostic workup, assisting patients in making an informed decision. However, patients with asymptomatic prostatitis cannot benefit from the use of this model since they cannot be pre-biopsy identified.We defined prostate-specific antigen (PSA) thresholds from a well calibrated risk prediction model for identifying and excluding advanced prostate cancer (PCa). We retrieved 902 biopsied patients with a pre-biopsy PSA determination (Roche assay). A logistic regression model predictive for PCa including the main effects [i.e., PSA, age, histological evidence of glandular inflammation (GI)] was built after testing the accuracy by calibration plots and Hosmer-Lemeshow test for goodness of fit. PSA thresholds were derived by assuming a diagnostic sensitivity of 95% (rule-out) and 80% (rule-in) for overall and advanced/poorly differentiated PCa. In patients without GI, serum PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa (defined as Gleason score ≥ 7 at biopsy), with a negative predictive value of 95.1% [95% confidence interval (CI): 83.0–98.7] and 88.8% (CI: 80.2–93.9), respectively, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) should address biopsy referral. In presence of GI, PSA did not provide a valid estimate for risk of advanced cancer because of its higher variability and the low pre-test probability of PCa. The proposed PSA thresholds may support biopsy decision except for patients with asymptomatic prostatitis who cannot be pre-biopsy identified.
Highlights
Released clinical practice guidelines (CPGs) no longer recommend decision thresholds of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) to rule in patients for prostate biopsy referral [1,2,3]
The American Cancer Society indicated a yearly PSA retesting for all patients with a value ≥ 2.5 μg/L at baseline, whereas other CPGs lowered the threshold to 1.0 μg/L, restricted the monitoring to men aged 55–69 years, and/or extended the time interval for PSA rescreening to 2–4 years [1,2,3,5]
Patients with PCa were older and had higher PSA values than those without the disease. Both age and serum PSA concentrations were significantly increased in Cancers 2021, 13, 3381 advanced stages of PCa, with ~80% of patients with advanced/poorly differentiated disease aged over 65 years
Summary
Released clinical practice guidelines (CPGs) no longer recommend decision thresholds of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) to rule in patients for prostate biopsy referral [1,2,3]. Some experts have asked how much accurate the estimate of the risk predicted at the individual level is, underlining the burden of unnecessary biopsies and the rate of missed aggressive cancer [13]. These drawbacks stress the use of a more rigorous research methodology, as well as the need to tune risk models to the current clinical goals in order to pragmatically fulfill the redesigned screening strategies. The predicted risk should inform an individual on the probability to exclude or detect an aggressive PCa, with an acceptable accuracy of recommending biopsy referral
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