Predictive Value of [−2]proPSA‐Related Indices for Prostate Cancer Detection Years Before Prostate‐Specific Antigen Elevation: Insights From a Five‐Year Longitudinal Screening Cohort
Yoshitaka Sekine, Yuji Fujizuka, Syun Nakazawa, Yusuke Tsuji, Akira Ohtsu, Yoshiyuki Miyazawa, Seiji Arai, Masashi Nomura, Hidekazu Koike, Hiroshi Matsui, Kazuto Ito, Kazuhiro SuzukiABSTRACT
Background
[‐2]proPSA(p2PSA)‐related indices have demonstrated diagnostic value for detecting prostate cancer (PC) in males with modest increases in prostate‐specific antigen levels (PSA) of < 10 ng/mL. However, the “leak point” of p2PSA level in the blood circulation before developing screen‐detectable PC remains uncertain. Therefore, this study evaluated the ability of p2PSA‐related indices in the years before considering conventional biopsy indications.
Methods
This case‐control study analyzed database and serum bank information from a population‐based screening cohort in Gunma Prefecture. The case group included 58 males diagnosed with PC due to increased PSA (4–10 ng/mL) followed serially for 5 years. The control group comprised 58 males without PC based on biopsy who were matched to the case group by adjusted PSA levels (± 2 ng/mL) and age (± 5 years) at the time of biopsy. p2PSA, free PSA, and PSA were measured from frozen serum samples from 0 to 5 years before biopsy.
Results
p2PSA‐to‐free PSA ratio (%p2PSA) and prostate health index (phi) were significantly higher in the case group than in the control group from five, three, and 3 years before biopsy, respectively. The areas under the receiver operating characteristic curve for predicting PC were 0.437 for PSA, 0.637 for phi, 0.663 for %p2PSA, and 0.618 for free PSA‐to PSA ratio (%fPSA) at 3 years before biopsy.
Conclusions
p2PSA‐related indices showed group‐level differences between future PC cases and matched controls before PSA exceeded conventional cut‐offs. These findings should be regarded as hypothesis‐generating and require validation in prospective studies before clinical application to risk‐stratified screening.