Personalised biopsy schedules based on risk of Gleason upgrading for patients with low-risk prostate cancer on active surveillance

Anirudh Tomer*, Daan Nieboer, Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) consortium, Monique J Roobol, Anders Bjartell, Ewout W Steyerberg, Dimitris Rizopoulos

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)96-107
Number of pages12
JournalBJU International
Volume127
Issue number1
Early online date12 Jun 2020
DOIs
Publication statusPublished - Jan 2021

Bibliographical note

Acknowledgements:
We thank Jozien Helleman from the Department of Urology, Erasmus University Medical Center, for coordinating the project. The first and last authors would like to acknowledge support by Nederlandse Organisatie voor Wetenschappelijk Onderzoek (the National Research Council of the Netherlands) VIDI grant nr. 016.146.301, and Erasmus University Medical Center funding. Part of this work was carried out on the Dutch national einfrastructure with the support of SURF Cooperative. The authors also thank the Erasmus University Medical Center’s Cancer Computational Biology Center for giving access to their IT-infrastructure and software that was used for the computations and data analysis in this study. The PRIAS website is funded by the Prostate Cancer Research Foundation, Rotterdam (SWOP). We would like to thank the PRIAS consortium for enabling this research project. This work was supported by the Movember Foundation. The funder did not play any role in the study design, collection, analysis or interpretation of data, or in the drafting of this paper.

© 2020 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

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