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Licensed Unlicensed Requires Authentication Published by De Gruyter January 27, 2023

Individual risk prediction of high grade prostate cancer based on the combination between total prostate-specific antigen (PSA) and free to total PSA ratio

  • Simona Ferraro EMAIL logo , Davide Biganzoli , Roberta Simona Rossi , Franco Palmisano , Marco Bussetti , Enrica Verzotti , Andrea Gregori , Filippo Bianchi , Marco Maggioni , Ferruccio Ceriotti ORCID logo , Cristina Cereda , Gianvincenzo Zuccotti , Peter Kavsak , Mario Plebani ORCID logo , Giuseppe Marano and Elia Mario Biganzoli EMAIL logo



Clinical practice guidelines endorse the stratification of prostate cancer (PCa) risk according to individual total prostate-specific antigen (tPSA) values and age to enhance the individual risk-benefit ratio. We defined two nomograms to predict the individual risk of high and low grade PCa by combining the assay of tPSA and %free/tPSA (%f/tPSA) in patients with a pre-biopsy tPSA between 2 and 10 μg/L.


The study cohort consisted of 662 patients that had fPSA, tPSA, and a biopsy performed (41.3% with a final diagnosis of PCa). Logistic regression including age, tPSA and %f/tPSA was used to model the probability of having high or low grade cancer by defining 3 outcome levels: no PCa, low grade (International Society of Urological Pathology grade, ISUP<3) and high grade PCa (ISUP≥3).


The nomogram identifying patients with: (a) high vs. those with low grade PCa and without the disease showed a good discriminating capability (∼80%), but the calibration showed a risk of underestimation for predictive probabilities >30% (a considerable critical threshold of risk), (b) ISUP<3 vs. those without the disease showed a discriminating capability of 63% and overestimates predictive probabilities >50%. In ISUP 5 a possible loss of PSA immunoreactivity has been observed.


The estimated risk of high or low grade PCa by the nomograms may be of aid in the decision-making process, in particular in the case of critical comorbidities and when the digital rectal examinations are inconclusive. The improved characterization of the risk of ISUP≥3 might enhance the use for magnetic resonance imaging in this setting.

Corresponding author: Simona Ferraro, Center of Functional Genomics and Rare Diseases, Department of Pediatrics, Buzzi Children’s Hospital, 20154 Milan, Italy, E-mail: ; and Elia Mario Biganzoli, Medical Statistics Unit, Department of Biomedical and Clinical Sciences L. Sacco, “Luigi Sacco” University Hospital, University of Milan, Milan, Italy, E-mail:
Simona Ferraro and Davide Biganzoli contributed equally to this work. Giuseppe Marano and Elia Mario Biganzoli contributed equally to this work as senior authors.
  1. Research funding: None declared.

  2. Author contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. SF and DB, were involved in the provision of study material and conceptualization; MB, EV, FP, RR, FC, FB, MM, GM, AG were involved in the provision of study material; EB, MP, PK, CC, GZ revised and corrected the final draft. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The Review Board of our institution approved the study, carried out according to the Helsinki Declaration of 1975, as revised in 1996.


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Supplementary Material

This article contains supplementary material (

Received: 2023-01-04
Accepted: 2023-01-19
Published Online: 2023-01-27
Published in Print: 2023-06-27

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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