  Background: Low-risk prostate cancer patients enrolled in active surveillance
programs commonly undergo biopsies for examination of cancer progression.
Biopsies are conducted as per a fixed and frequent schedule (e.g., annual
biopsies). Since biopsies are burdensome, patients do not always comply with
the schedule, which increases the risk of delayed detection of cancer
progression.
  Objective: Our aim is to better balance the number of biopsies (burden) and
the delay in detection of cancer progression (less is beneficial), by
personalizing the decision of conducting biopsies.
  Data Sources: We use patient data of the world's largest active surveillance
program (PRIAS). It enrolled 5270 patients, had 866 cancer progressions, and an
average of nine prostate-specific antigen (PSA) and five digital rectal
examination (DRE) measurements per patient.
  Methods: Using joint models for time-to-event and longitudinal data, we model
the historical DRE and PSA measurements, and biopsy results of a patient at
each follow-up visit. This results in a visit and patient-specific cumulative
risk of cancer progression. If this risk is above a certain threshold, we
schedule a biopsy. We compare this personalized approach with the currently
practiced biopsy schedules via an extensive and realistic simulation study,
based on a replica of the patients from the PRIAS program.
  Results: The personalized approach saved a median of six biopsies (median: 4,
IQR: 2-5), compared to the annual schedule (median: 10, IQR: 3-10). However,
the delay in detection of progression (years) is similar for the personalized
(median: 0.7, IQR: 0.3-1.0) and the annual schedule (median: 0.5, IQR:
0.3-0.8).
  Conclusions: We conclude that personalized schedules provide substantially
better balance in the number of biopsies per detected progression for men with
low-risk prostate cancer.
