Personalised biopsy schedules based on risk of Gleason upgrading for patients with low‐risk prostate cancer on active surveillance. (1st August 2020)

• Record Type: Journal Article
• Authors: Tomer, Anirudh; Nieboer, Daan; Roobol, Monique J.; Bjartell, Anders; Steyerberg, Ewout W.; Rizopoulos, Dimitris
• Other Names: Trock Bruce investigator.; Ehdaie Behfar investigator.; Carroll Peter investigator.; Filson Christopher investigator.; Kim Jeri investigator.; Logothetis Christopher investigator.; Morgan Todd investigator.; Klotz Laurence investigator.; Pickles Tom investigator.; Hyndman Eric investigator.; Moore Caroline investigator.; Gnanapragasam Vincent investigator.; Van Hemelrijck Mieke investigator.; Dasgupta Prokar investigator.; Bangma Chris investigator.; Villers Arnauld investigator.; Rannikko Antti investigator.; Valdagni Riccardo investigator.; Perry Antoinette investigator.; Hugosson Jonas investigator.; Rubio‐Briones Jose investigator.; Hefermehl Lukas investigator.; Shiong Lee Lui investigator.; Frydenberg Mark investigator.; Kakehi Yoshiyuki investigator.; Sugimoto Mikio investigator.; van der Kwast Theo investigator.; Obbink Henk investigator.; van der Linden Wim investigator.; Hulsen Tim investigator.; de Jonge Cees investigator.; Kattan Mike investigator.; Xinge Ji investigator.; Muir Kenneth investigator.; Lophatananon Artitaya investigator.; Fahey Michael investigator.; Zhang Liying investigator.; Beckmann Kerri investigator.; Denton Brian investigator.; Hayen Andrew investigator.; Boutros Paul investigator.; Guo Wei investigator.; Benfante Nicole investigator.; Cowan Janet investigator.; Patil Dattatraya investigator.; Tolosa Emily investigator.; Kim Tae‐Kyung investigator.; Mamedov Alexandre investigator.; LaPointe Vincent investigator.; Crump Trafford investigator.; Stavrinides Vasilis investigator.; Kimberly‐Duffell Jenna investigator.; Santaolalla Aida investigator.; Olivier Jonathan investigator.; Rancati Tiziana investigator.; Ahlgren Helén investigator.; Mascarós Juanma investigator.; Löfgren Annica investigator.; Lehmann Kurt investigator.; Lin Catherine Han investigator.; Hirama Hiromi investigator.; Lee Kwang Suk investigator.; Jenster Guido investigator.; Auvinen Anssi investigator.; Haider Masoom investigator.; van Bochove Kees investigator.; Carter Ballentine investigator.; Gledhill Sam investigator.; Buzza Mark investigator.; Kouspou Michelle investigator.; Bruinsma Sophie investigator.; Helleman Jozien investigator.;
• Is Part Of: BJU international. Volume 127:Number 1(2021)
• Page Start: 96
• Page End: 107
• Publication Date: 2020-08-01
• Subjects: active surveillance -- biopsies -- personalised medicine -- prostate cancer -- shared decision‐making; Genitourinary organs -- Diseases -- Periodicals; Genitourinary organs -- Surgery -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1111/bju.15136
• Languages: English
• ISSNs: 1464-4096

Abstract

Abstract : Objective: To develop a model and methodology for predicting the risk of Gleason upgrading in patients with prostate cancer on active surveillance (AS) and using the predicted risks to create risk‐based personalised biopsy schedules as an alternative to one‐size‐fits‐all schedules (e.g. annually). Furthermore, to assist patients and doctors in making shared decisions on biopsy schedules, by providing them quantitative estimates of the burden and benefit of opting for personalised vs any other schedule in AS. Lastly, to externally validate our model and implement it along with personalised schedules in a ready to use web‐application. Patients and Methods: Repeat prostate‐specific antigen (PSA) measurements, timing and results of previous biopsies, and age at baseline from the world's largest AS study, Prostate Cancer Research International Active Surveillance (PRIAS; 7813 patients, 1134 experienced upgrading). We fitted a Bayesian joint model for time‐to‐event and longitudinal data to this dataset. We then validated our model externally in the largest six AS cohorts of the Movember Foundation's third Global Action Plan (GAP3) database (>20 000 patients, 27 centres worldwide). Using the model predicted upgrading risks; we scheduled biopsies whenever a patient's upgrading risk was above a certain threshold. To assist patients/doctors in the choice of this threshold, and to compare the resulting personalised schedule with currently practiced schedules, along with the timing and the total number of biopsies (burden) planned, for each schedule we provided them with the time delay expected in detecting upgrading (shorter is better). Results: The cause‐specific cumulative upgrading risk at the 5‐year follow‐up was 35% in PRIAS, and at most 50% in the GAP3 cohorts. In the PRIAS‐based model, PSA velocity was a stronger predictor of upgrading (hazard ratio [HR] 2.47, 95% confidence interval [CI] 1.93–2.99) than the PSA level (HR 0.99, 95% CI 0.89–1.11). Our model had a moderate area under the receiver operating characteristic curve (0.6–0.7) in the validation cohorts. The prediction error was moderate (0.1–0.2) in theGAP3 cohorts where the impact of the PSA level and velocity on upgrading risk was similar to PRIAS, but large (0.2–0.3) otherwise. Our model required re‐calibration of baseline upgrading risk in the validation cohorts. We implemented the validated models and the methodology for personalised schedules in a web‐application (http://tiny.cc/biopsy ). Conclusions: We successfully developed and validated a model for predicting upgrading risk, and providing risk‐based personalised biopsy decisions in AS of prostate cancer. Personalised prostate biopsies are a novel alternative to fixed one‐size‐fits‐all schedules, which may help to reduce unnecessary prostate biopsies, while maintaining cancer control. The model and schedules made available via a web‐application enable shared decision‐making on biopsy schedules by comparing fixed and personalised schedules on total biopsies and expected time delay in detecting upgrading.