When to order genomic tests: development and external validation of a model to predict high-risk prostate cancer at the genotypic level.

The aim of this study was to develop a model to predict high-genomic-risk prostate cancer (PCa) according to Decipher score, a validated 22 gene prognostic panel. By doing so, one might select the individuals who are likely to benefit from genomic testing and improve pre-op counseling about the need for adjuvant treatments.

We retrospectively reviewed IRB-approved databases at two institutions. All patients had preoperative magnetic resonance imaging (MRI) and Decipher prostate radical prostatectomy (RP), a validated 22 gene prognostic panel. We used binary logistic regression to estimate high-risk Decipher (Decipher score > 0.60) probability on RP specimen. Area under the curve (AUC) and calibration were used to assess the accuracy of the model in the development and validation cohort. Decision curve analysis (DCA) was performed to assess the clinical benefit of the model.

The development and validation cohort included 622 and 185 patients with 283 (35%) and 80 (43%) of those with high-risk Decipher. The multivariable model included PSA density, biopsy Gleason Grade Group, percentage of positive cores and MRI extracapsular extension. AUC was 0.73 after leave-one-out cross-validation. DCA showed a clinical benefit in a range of probabilities between 15 and 60%. In the external validation cohort, AUC was 0.70 and calibration showed that the model underestimates the actual probability of the outcome.

The proposed model to predict high-risk Decipher score at RP is helpful to improve risk stratification of patients with PCa and to assess the need for additional testing and treatments.

World journal of urology. 2022 Dec 09 [Epub ahead of print]

Ugo Giovanni Falagario, Dimple Chakravarty, Alberto Martini, Mohammed Shahait, Ayah El-Fahmawi, Ivan Jambor, Anna Lantz, David Grannas, Parita Ratnani, Sneha Parekh, Dara Lundon, Kenneth Haines, Luigi Cormio, Giuseppe Carrieri, Natasha Kyprianou, Michael W Kattan, Eric A Klein, Peter Wiklund, David I Lee, Ash Tewari

Department of Urology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, 6th Floor, New York City, NY, 10029, USA. ., Department of Urology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, 6th Floor, New York City, NY, 10029, USA., Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy., Department of Surgery, King Hussein Cancer Center, Amman, Jordan., Department of Surgery, Urology Division, University of Pennsylvania, Philadelphia, USA., Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, USA., Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden., Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, USA., Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy., Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland, USA., Department of Urology, Glickman Urological and Kidney Institute, Cleveland, USA., Department of Urology, University of California Irvine, Irvine, USA.