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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., Competing Interests: Declarations. Ethical approval: Appropriate ethics approval was obtained from the University Health Network research ethics board. Previous presentations: None. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In Canada and across the globe, access to PSMA PET/CT is limited and expensive. For patients with biochemical recurrence (BCR) after treatment for prostate cancer, novel strategies are needed to better stratify patients who may or may not benefit from a PSMA PET scan. The role of the free-to-total prostate-specific antigen (PSA) ratio (FPSAR) in posttreatment prostate cancer, specifically in the PSMA PET/CT era, remains unknown. Our aim in this study was to determine the association of FPSAR in patients referred for 18 F-DCFPyL PSMA PET/CT in the BCR setting and assess the correlation between FPSAR and 18 F-DCFPyL PSMA PET/CT positivity (local recurrence or distant metastases). Methods: This prospective study included 137 patients who were referred for 18 F-DCFPyL PSMA PET/CT and had BCR with a total PSA of less than 1 ng/mL after radical prostatectomy (RP) (including adjuvant or salvage radiotherapy). Blood samples were collected on the day of 18 F-DCFPyL PSMA PET/CT. FPSAR was categorized as less than 0.10 or as 0.10 or more. A positive 18 F-DCFPyL PSMA PET/CT scan was defined by a PROMISE classification lesion score of 2 or 3, irrespective of the site of increased tracer uptake (e.g., prostate, pelvic nodes, bone, or viscera). Results: Overall, 137 blood samples of patients with BCR after RP were analyzed to calculate FPSAR. The median age at 18 F-DCFPyL PSMA PET/CT was 68.6 y (interquartile range, 63.0-72.4 y), and the median PSA at 18 F-DCFPyL PSMA PET/CT was 0.3 ng/mL (interquartile range, 0.3-0.6 ng/mL). Eighty-six patients (62.8%) had an FPSAR of less than 0.10, whereas 51 patients (37.2%) had an FPSAR of 0.10 or more. An FPSAR of 0.10 or more was identified as an independent predictor of a positive 18 F-DCFPyL PSMA PET/CT scan, with an odds ratio of 6.99 (95% CI, 2.96-16.51; P < 0.001). Conclusion: An FPSAR of 0.10 or more after RP independently correlated with increased odds of a positive 18 F-DCFPyL PSMA PET/CT scan among BCR post-RP patients. These findings may offer an inexpensive method by which to triage access to 18 F-DCFPyL PSMA PET/CT in jurisdictions where availability is not replete., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)