Expanding Active Surveillance Criteria for Low- and Intermediate-risk Prostate Cancer: Can We Accurately Predict the Risk of Misclassification for Patients Diagnosed by Multiparametric Magnetic Resonance Imaging-targeted Biopsy

Active surveillance (AS) is generally recognized as the preferred treatment option for low-risk prostate cancer (PCa) patients with excellent long-term oncologic outcomes, preserving quality of life and functional outcomes. Recent data have suggested expanding indication to highly selected favorable intermediate-risk PCa although associated with a higher risk of progression to locally advanced and metastatic disease. Defining optimal selection criteria remains a key issue. Recently Gandaglia et al., on behalf of the European Association of Urology-Young Academic Urologists Working Party on Prostate Cancer, and Lantz et al. developed multivariable models predicting the risk of adverse pathology (i.e., ISUP grade group≥3, non-organ confined disease and/or lymph node invasion) among patients operated by radical prostatectomy for low- and intermediate-risk PCa. We aimed to test these models in a set of 1062 low- and favorable intermediate-risk PCa patients diagnosed by multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy using Trinity (Koelis®, La Tronche, France) system. We hypothesized that inclusion of radiological features into a novel model would improve patient selection. Performance was assessed using discrimination, calibration, and decision-curve-analysis (DCA).

Available models were characterized by poor discrimination (area under the receiver operating characteristic curve (AUC) of 59% and 60%), underestimation of predicted risk on calibration plots and a small amount of net benefit against probability-threshold of 40%-50% at DCA. The development of a novel model including preoperative PSA, clinical T-stage at MRI, PI-RADS score, percentage of csPCa cores and ISUP grade group slightly improved discrimination (AUC of 63% vs 59%, p=0.001, and 63% vs 60%, p=0.07) and net benefit against threshold probabilities of ≥30%.

This first multicentric study demonstrated the poor performance of models predicting adverse pathology and that implementation of MRI and MRI-targeted biopsy in this setting was not associated with a clear improvement in patient selection. Although such covariates have already been evaluated as encouraging criteria for patient selection and monitoring, further studies integrating new biomarkers are awaited. Inclusion of serum (e.g., Prostate Health Index, 4KScore), urinary (e.g., prostate cancer antigen 3) and tissue-based (i.e., Oncotype DX Genomic Prostate Score®, Prolaris® Cell Cycle Progression score, GenomeDx Decipher® score, and Promark® score) biomarkers in predictive models could improve patient selection and monitoring for AS, albeit most of them are still under investigation and their accessibility remains limited in terms of cost and availability in clinical practice.

In conclusion, we found that patients harboring low- or favorable intermediate-risk PCa and candidates for radical prostatectomy cannot be accurately referred to an AS program without a non-negligible risk of misclassification.

Written by: Romain Diamand, Simone Albisinni, Jean-Baptiste Roche, Elena Lievore, Vito Lacetera, Giuseppe Chiacchio, Valerio Beatrici, Riccardo Mastroianni, Giuseppe Simone, Olivier Windisch, Daniel Benamran, Alexandre Fourcade, Truong An Nguyen, Georges Fournier, Gaelle Fiard, Guillaume Ploussard, Alexandre Peltier, Thierry Roumeguère

Department of Urology, Jules Bordet Institute-Erasme Hospital, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium. Department of Urology, Jules Bordet Institute-Erasme Hospital, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium., Department of Urology, Clinique Saint-Augustin, Bordeaux, France., Department of Urology, Clinique Saint-Augustin, Bordeaux, France; Department of Urology, IRCCS IEO Istituto Europeo di Oncologia, Milan, Italy., Department of Urology, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Pesaro, Italy., Department of Urology, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy., Department of Urology, Hôpitaux Universitaires de Genève, Geneva, Switzerland., Department of Urology, Hôpital Cavale Blanche, CHRU Brest, Brest, France., Department of Urology, Grenoble Alpes University Hospital, Université Grenoble Alpes, CNRS, Grenoble INP, TIMC, Grenoble, France., Department of Urology, La Croix du Sud Hospital, Quint Fonsegrives, France.

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