Can the free/total psa ratio predict undetected intraductal carcinoma and cribriform pattern at biopsy?

Background: Intraductal carcinoma (IDC) and cribriform pattern (Crib) of prostate cancer are recognised as independent prognosticators of poor outcome, both in prostate biopsies and radical prostatectomy (RP) specimens.

Objective: This study aimed to determine the predictive value of Free-to-total PSA ratio (FPSAR) in identifying missed IDC/Crib at the time of biopsy as compared to the final surgical specimen.

Materials and methods: Patients who underwent RP between January 2015 and December 2022 were included in the study. Predictors of a false negative biopsy were examined using a multivariate logistic regression. Associations between true positive/true negative/false negative biopsies (for IDC/Crib) with FPSAR as primary outcome parameter were determined using Chi-squared test and Kruskal-Wallis test.

Results: This study included 639 patients who underwent radical prostatectomy between 2015 and 2022 (Table 1) and had available FPSAR- at the time of biopsy. The median age was 63.0 years (IQR: 58.9-68.0). The median serum PSA before RP was 7.0 ng/ml (IQR: 5.3-9.5). Among the 639 patients, 177 (28%) had Crib, and 97 (15%) had IDC on prostate biopsy, with 54 (9%) patients having both IDC and Crib. Concerning Grade Group distribution at biopsy, there was: GG1 in 62 patients (10%), GG2 in 428 (67%), GG3 in 102 (16%), GG4 in 28 (4%), and GG5 in 19 (3%) patients. On multivariate regression analysis, the following were associated with lower odds of a false-negative IDC/Crib biopsy: Percentage of pattern 4 ≥ 10% at biopsy (odds ratio [OR] 0.17, 95% CI 0.10-0.29; p < 0.001); higher Gleason score (grade group 4/5) on biopsy (OR 0.38, 95% CI 0.16-0.91; p = 0.03) and higher percent of positive cores at biopsy ≥ 33% (OR 0.51, 95% CI 0.29-0.88; p = 0.02). FPSAR ≥ 0.10 was not an independent predictor of a false-negative IDC/Crib biopsy (p > 0.05).

Conclusions: In conclusion, our study's findings suggest that FPSAR is not a reliable biomarker for identifying IDC/Crib status at the time of biopsy. Further research is needed to identify biomarkers or combinations of biomarkers that can improve the diagnostic accuracy for these aggressive variants of PCa. Our study that involved 639 patients shows that FPSAR is not a good marker for detecting aggressive types of PCa, during a biopsy. More research is needed to find better markers or combinations of markers that can help diagnose these aggressive forms of prostate cancer more accurately.