Is pre-biopsy serum prostate specific antigen retesting always justified? A study of the influence of individual and analytical factors on decision making for biopsy referral

Definition of Outcome-Based Prostate-Specific Antigen (PSA) Thresholds for Advanced Prostate Cancer Risk Prediction

“…Our evidence is aligned with other research data reporting that only ≤20% of men undergoing screening with PSA in the range 2.6–4.0 µg/L harbored a Gleason score ≥ 7 PCa [ 14 , 19 , 35 ]. On the other hand, the evidence suggests that rescreening men aged <65 years with PSA at baseline > 4.0 µg/L for active surveillance of low-grade disease may have a favorable risk-benefit balance if performed biennially [ 2 ], in particular considering: (a) the slow growth of PCa of any histological grade, and (b) the reference change value of ~20% useful to identify intraindividual PSA changes overtime significantly turning into clinically relevance [ 25 , 36 , 37 ]. Taking that into account, in our study, PSA values between 4.1 and 4.9 µg/L consistently excluded aggressive PCa (NPV, 97.5%), therefore suggesting to place these patients under active surveillance with a biennial PSA retesting ( Figure 2 ).…”

“…In our study, we were unable to define PSA risk thresholds for advanced cancer and biopsy referral in patients displaying glandular inflammation. This was due to the known low prevalence of PCa in this subgroup of patients and to the variable effect of the inflammatory status on the increase of PSA concentrations in serum [ 21 , 32 , 36 ]. This could not be circumvented by collapsing these partitions, since ROC curves built on the full model may consequently deviate from the monotonic function.…”

“…PSA measurements were carried out using an electrochemiluminescence immunoassay marketed by Roche Diagnostics, whose characteristics have been previously described in detail [ 36 ]. PSA for patients enrolled until 2017 were assayed on a Cobas e601 platform, while in the last three years the newly released Cobas e801 analyzer was employed.…”

“…PSA for patients enrolled until 2017 were assayed on a Cobas e601 platform, while in the last three years the newly released Cobas e801 analyzer was employed. Results from the two systems were nicely aligned [ 36 ]. The review board of our institution approved the study, carried out according to the Helsinki Declaration of 1975, as revised in 1996.…”

“…The required sample size was estimated according to a simulation based on previously published data [ 36 ], by setting µ1 = 6.7 μg/L and µ2 = 5.5 μg/L as means of distribution of PSA values in patients with and without PCa in the referral population, a SD σ = 3.5 μg/L, one-sided test option, α = 0.05, and a power of 0.80 [ 45 ]. By considering a maximum of 5 theoretical partitions of clinical interest, a final sample size of 800 patients may prompt to a well powered investigation, as also confirmed by the available evidence [ 15 ].…”