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Systematic review and meta-analysis of factors determining change to radical treatment in active surveillance for localized prostate cancer

  • Andrew J. Simpkin 1,
  • Kate Tilling 1,
  • Richard M. Martin 1,
  • J. Athene Lane 1,
  • Freddie C. Hamdy 3,
  • Lars Holmberg 4,
  • David E. Neal 5,
  • Chris Metcalfe 1,
  • Jenny L. Donovan 1
1 School of Social and Community Medicine, University of Bristol, Bristol, UK 3 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK 4 Guy's Hospital, London, UK 5 Cancer Research UK, Cambridge Research Institute, Cambridge, UK

Take home message

We identified 26 studies including 7627 men on active surveillance. There were few prostate cancer deaths. Programs with a scheduled rebiopsy and including only men with Gleason 3 + 3 scores had the highest rates of change to radical treatment.

Publication: Eur Urol., Volume 67, Issue 6, June 2015, Pages 993-1005

PII: S0302-2838(15)00018-4

DOI: 10.1016/j.eururo.2015.01.004

Context

Many men with clinically localized prostate cancer are being monitored as part of active surveillance (AS) programs, but little is known about reasons for receiving radical treatment.

Objectives

A systematic review of the evidence about AS was undertaken, with a meta-analysis to identify predictors of radical treatment.

Evidence acquisition

A comprehensive search of the Embase, MEDLINE and Web of Knowledge databases to March 2014 was performed. Studies reporting on men with localized prostate cancer followed by AS or monitoring were included. AS was defined where objective eligibility criteria, management strategies, and triggers for clinical review or radical treatment were reported.

Evidence synthesis

The 26 AS cohorts included 7627 men, with a median follow-up of 3.5 yr (range of medians 1.5–7.5 yr). The cohorts had a wide range of inclusion criteria, monitoring protocols, and triggers for radical treatment. There were eight prostate cancer deaths and five cases of metastases in 24 981 person-years of follow-up. Each year, 8.8% of men (95% confidence interval 6.7–11.0%) received radical treatment, most commonly because of biopsy findings, prostate-specific antigen triggers, or patient choice driven by anxiety. Studies in which most men changed treatment were those including only low-risk Gleason score 6 disease and scheduled rebiopsies.

Conclusions

The wide variety of AS protocols and lack of robust evidence make firm conclusions difficult. Currently, patients and clinicians have to make judgments about the balance of risks and benefits in AS protocols. The publication of robust evidence from randomized trials and longer-term follow-up of cohorts is urgently required.

Patient summary

We reviewed 26 studies of men on active surveillance for prostate cancer. There was evidence that studies including men with the lowest risk disease and scheduled rebiopsy had higher rates of radical treatment.

Commented by Henk van der Poel

Most crucial question: are patients that opt for active surveillance at increased risk of progression after local treatment for their prostate cancer? The different criteria used for prediction of inclusion and progression in 26 studies resulted in an active treatment rate of 1-22% per person year. Indications for change to active treatment were ranged, but at forest plot analysis rebiopsy gleason grade was the most frequently reported indication for active treatment in almost 40%. Follow up was short (<5y) which suggests that the observed upgrading is more due to undersampling than biological progression.