PMID- 32531869 OWN - NLM STAT- MEDLINE DCOM- 20210426 LR - 20230322 IS - 1464-410X (Electronic) IS - 1464-4096 (Print) IS - 1464-4096 (Linking) VI - 127 IP - 1 DP - 2021 Jan TI - Personalised biopsy schedules based on risk of Gleason upgrading for patients with low-risk prostate cancer on active surveillance. PG - 96-107 LID - 10.1111/bju.15136 [doi] AB - 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. CI - (c) 2020 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International. FAU - Tomer, Anirudh AU - Tomer A AD - Department of Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Nieboer, Daan AU - Nieboer D AD - Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands. AD - Department of Urology, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Roobol, Monique J AU - Roobol MJ AUID- ORCID: 0000-0001-6967-1708 AD - Department of Urology, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Bjartell, Anders AU - Bjartell A AD - Department of Urology, Skane University Hospital, Malmo, Sweden. FAU - Steyerberg, Ewout W AU - Steyerberg EW AD - Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands. AD - Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands. FAU - Rizopoulos, Dimitris AU - Rizopoulos D AD - Department of Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands. CN - Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) consortium LA - eng GR - MR/S005897/1/MRC_/Medical Research Council/United Kingdom GR - 016.146.301/Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ GR - Movember Foundation/ GR - Erasmus University Medical Center/ GR - Prostate Cancer Research Foundation/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Validation Study DEP - 20200801 PL - England TA - BJU Int JT - BJU international JID - 100886721 RN - EC 3.4.21.77 (Prostate-Specific Antigen) SB - IM MH - Aged MH - Appointments and Schedules MH - Area Under Curve MH - *Biopsy MH - Clinical Decision-Making MH - Decision Making, Shared MH - Humans MH - Internet MH - Male MH - Middle Aged MH - *Models, Statistical MH - Neoplasm Grading MH - Prostate/pathology MH - Prostate-Specific Antigen/blood MH - Prostatic Neoplasms/blood/*pathology/*therapy MH - ROC Curve MH - Risk Assessment/methods MH - Risk Factors MH - Software MH - *Watchful Waiting PMC - PMC7818468 OTO - NOTNLM OT - active surveillance OT - biopsies OT - personalised medicine OT - prostate cancer OT - shared decision-making COIS- The authors do not report any conflict of interest, and have nothing to disclose. FIR - Trock, Bruce IR - Trock B FIR - Ehdaie, Behfar IR - Ehdaie B FIR - Carroll, Peter IR - Carroll P FIR - Filson, Christopher IR - Filson C FIR - Kim, Jeri IR - Kim J FIR - Logothetis, Christopher IR - Logothetis C FIR - Morgan, Todd IR - Morgan T FIR - Klotz, Laurence IR - Klotz L FIR - Pickles, Tom IR - Pickles T FIR - Hyndman, Eric IR - Hyndman E FIR - Moore, Caroline IR - Moore C FIR - Gnanapragasam, Vincent IR - Gnanapragasam V FIR - Van Hemelrijck, Mieke IR - Van Hemelrijck M FIR - Dasgupta, Prokar IR - Dasgupta P FIR - Bangma, Chris IR - Bangma C FIR - Villers, Arnauld IR - Villers A FIR - Rannikko, Antti IR - Rannikko A FIR - Valdagni, Riccardo IR - Valdagni R FIR - Perry, Antoinette IR - Perry A FIR - Hugosson, Jonas IR - Hugosson J FIR - Rubio-Briones, Jose IR - Rubio-Briones J FIR - Hefermehl, Lukas IR - Hefermehl L FIR - Shiong, Lee Lui IR - Shiong LL FIR - Frydenberg, Mark IR - Frydenberg M FIR - Kakehi, Yoshiyuki IR - Kakehi Y FIR - Sugimoto, Mikio IR - Sugimoto M FIR - van der Kwast, Theo IR - van der Kwast T FIR - Obbink, Henk IR - Obbink H FIR - van der Linden, Wim IR - van der Linden W FIR - Hulsen, Tim IR - Hulsen T FIR - de Jonge, Cees IR - de Jonge C FIR - Kattan, Mike IR - Kattan M FIR - Xinge, Ji IR - Xinge J FIR - Muir, Kenneth IR - Muir K FIR - Lophatananon, Artitaya IR - Lophatananon A FIR - Fahey, Michael IR - Fahey M FIR - Zhang, Liying IR - Zhang L FIR - Beckmann, Kerri IR - Beckmann K FIR - Denton, Brian IR - Denton B FIR - Hayen, Andrew IR - Hayen A FIR - Boutros, Paul IR - Boutros P FIR - Guo, Wei IR - Guo W FIR - Benfante, Nicole IR - Benfante N FIR - Cowan, Janet IR - Cowan J FIR - Patil, Dattatraya IR - Patil D FIR - Tolosa, Emily IR - Tolosa E FIR - Kim, Tae-Kyung IR - Kim TK FIR - Mamedov, Alexandre IR - Mamedov A FIR - LaPointe, Vincent IR - LaPointe V FIR - Crump, Trafford IR - Crump T FIR - Stavrinides, Vasilis IR - Stavrinides V FIR - Kimberly-Duffell, Jenna IR - Kimberly-Duffell J FIR - Santaolalla, Aida IR - Santaolalla A FIR - Olivier, Jonathan IR - Olivier J FIR - Rancati, Tiziana IR - Rancati T FIR - Ahlgren, Helen IR - Ahlgren H FIR - Mascaros, Juanma IR - Mascaros J FIR - Lofgren, Annica IR - Lofgren A FIR - Lehmann, Kurt IR - Lehmann K FIR - Lin, Catherine Han IR - Lin CH FIR - Hirama, Hiromi IR - Hirama H FIR - Lee, Kwang Suk IR - Lee KS FIR - Jenster, Guido IR - Jenster G FIR - Auvinen, Anssi IR - Auvinen A FIR - Haider, Masoom IR - Haider M FIR - van Bochove, Kees IR - van Bochove K FIR - Carter, Ballentine IR - Carter B FIR - Gledhill, Sam IR - Gledhill S FIR - Buzza, Mark IR - Buzza M FIR - Kouspou, Michelle IR - Kouspou M FIR - Bruinsma, Sophie IR - Bruinsma S FIR - Helleman, Jozien IR - Helleman J EDAT- 2020/06/13 06:00 MHDA- 2021/04/27 06:00 PMCR- 2021/01/21 CRDT- 2020/06/13 06:00 PHST- 2020/05/31 00:00 [accepted] PHST- 2020/06/13 06:00 [pubmed] PHST- 2021/04/27 06:00 [medline] PHST- 2020/06/13 06:00 [entrez] PHST- 2021/01/21 00:00 [pmc-release] AID - BJU15136 [pii] AID - 10.1111/bju.15136 [doi] PST - ppublish SO - BJU Int. 2021 Jan;127(1):96-107. doi: 10.1111/bju.15136. Epub 2020 Aug 1.