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Sources of Funding: This work was supported by the National Science Foundation (CMMI 0844511 to BTD, DGE 1256260 to CLB); any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. _x000D_

Introduction

Active surveillance (AS) for prostate cancer (CaP) involves close follow-up with serial prostate biopsies. The optimal biopsy frequency during follow-up has not been determined, resulting in variation in practice. The goal of this investigation was to use longitudinal AS biopsy data to assess if the frequency of biopsy could be reduced without substantially prolonging the time to detection of Gleason ≥ 7 disease.

Methods

Using data from 1,500 men with very-low or low-risk CaP enrolled in AS at Johns Hopkins, we developed a hidden Markov model to estimate the probability of under sampling, the annual probability of grade progression to Gleason ≥ 7 and the 10-year cumulative probability of reclassification or progression to Gleason ≥ 7. We then simulated 1024 potential AS biopsy strategies where it was assumed a biopsy would or would not be performed each year for the 10 years following diagnosis. For each of these strategies the model was used to predict the average delay in detection of Gleason ≥ 7 disease, which was compared across strategies to identify potential alternatives to annual biopsy.

Results

The model estimated 10-year cumulative probability of reclassification from Gleason 6 to Gleason ≥ 7 was 46.0%. The probability of under sampling at diagnosis was 9.8% and the annual progression probability for men with Gleason 6 was 4.0%. Based on these estimates, simulation of an annual biopsy strategy estimated the mean time to detection of Gleason ≥ 7 disease to be 14.1 months. Alternative strategies that reduced the number of biopsies increased the time to detecting grade progression by 1.2 to 38.0 months; however, several strategies eliminated biopsies with only small (< 5 months) delays in detecting grade progression (Figure - Simulated increase in time to detecting grade progression based on number of biopsies eliminated from annual biopsy routine. Each point represents a unique AS biopsy strategy. Biopsies during a 10 year period would occur as indicated in the legend.)

Conclusions

While annual biopsy for low-risk men on AS is associated with the shortest time to detection of Gleason ≥ 7 disease, several alternative strategies may allow for less frequent biopsy without sizable increases in time to detecting grade progression.

Funding

This work was supported by the National Science Foundation (CMMI 0844511 to BTD, DGE 1256260 to CLB); any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. _x000D_