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Using prognosis to guide inclusion criteria, define standardised endpoints and stratify follow-up in active surveillance for prostate cancer.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Gnanapragasam, Vincent J  ORCID logo  https://orcid.org/0000-0003-4722-4207
Barrett, Tristan 
Thankapannair, Vineetha 
Rubio-Briones, Jose 

Abstract

OBJECTIVES: To test whether using disease prognosis can inform a rational approach to active surveillance (AS) for early prostate cancer. PATIENTS AND METHODS: We previously developed the Cambridge Prognostics Groups (CPG) classification, a five-tiered model that uses prostate-specific antigen (PSA), Grade Group and Stage to predict cancer survival outcomes. We applied the CPG model to a UK and a Swedish prostate cancer cohort to test differences in prostate cancer mortality (PCM) in men managed conservatively or by upfront treatment in CPG2 and 3 (which subdivides the intermediate-risk classification) vs CPG1 (low-risk). We then applied the CPG model to a contemporary UK AS cohort, which was optimally characterised at baseline for disease burden, to identify predictors of true prognostic progression. Results were re-tested in an external AS cohort from Spain. RESULTS: In a UK cohort (n = 3659) the 10-year PCM was 2.3% in CPG1, 1.5%/3.5% in treated/untreated CPG2, and 1.9%/8.6% in treated/untreated CPG3. In the Swedish cohort (n = 27 942) the10-year PCM was 1.0% in CPG1, 2.2%/2.7% in treated/untreated CPG2, and 6.1%/12.5% in treated/untreated CPG3. We then tested using progression to CPG3 as a hard endpoint in a modern AS cohort (n = 133). During follow-up (median 3.5 years) only 6% (eight of 133) progressed to CPG3. Predictors of progression were a PSA density ≥0.15 ng/mL/mL and CPG2 at diagnosis. Progression occurred in 1%, 8% and 21% of men with neither factor, only one, or both, respectively. In an independent Spanish AS cohort (n = 143) the corresponding rates were 3%, 10% and 14%, respectively. CONCLUSION: Using disease prognosis allows a rational approach to inclusion criteria, discontinuation triggers and risk-stratified management in AS.

Description

Keywords

#PCSM, #ProstateCancer, Active surveillance, Cambridge Prognostic Groups, Intermediate-risk, Localised prostate cancer, Low-risk, Stratified follow-up, Aged, Disease Progression, Humans, Male, Middle Aged, Neoplasm Grading, Prognosis, Prostatic Neoplasms, Retrospective Studies, Watchful Waiting

Journal Title

BJU Int

Conference Name

Journal ISSN

1464-4096
1464-410X

Volume Title

124

Publisher

Wiley

Rights

All rights reserved