Individual prognosis at diagnosis in nonmetastatic prostate cancer: Development and external validation of the PREDICT Prostate multivariable model

PLoS Med. 2019 Mar 12;16(3):e1002758. doi: 10.1371/journal.pmed.1002758. eCollection 2019 Mar.

Abstract

Background: Prognostic stratification is the cornerstone of management in nonmetastatic prostate cancer (PCa). However, existing prognostic models are inadequate-often using treatment outcomes rather than survival, stratifying by broad heterogeneous groups and using heavily treated cohorts. To address this unmet need, we developed an individualised prognostic model that contextualises PCa-specific mortality (PCSM) against other cause mortality, and estimates the impact of treatment on survival.

Methods and findings: Using records from the United Kingdom National Cancer Registration and Analysis Service (NCRAS), data were collated for 10,089 men diagnosed with nonmetastatic PCa between 2000 and 2010 in Eastern England. Median follow-up was 9.8 years with 3,829 deaths (1,202 PCa specific). Totals of 19.8%, 14.1%, 34.6%, and 31.5% of men underwent conservative management, prostatectomy, radiotherapy (RT), and androgen deprivation monotherapy, respectively. A total of 2,546 men diagnosed in Singapore over a similar time period represented an external validation cohort. Data were randomly split 70:30 into model development and validation cohorts. Fifteen-year PCSM and non-PCa mortality (NPCM) were explored using separate multivariable Cox models within a competing risks framework. Fractional polynomials (FPs) were utilised to fit continuous variables and baseline hazards. Model accuracy was assessed by discrimination and calibration using the Harrell C-index and chi-squared goodness of fit, respectively, within both validation cohorts. A multivariable model estimating individualised 10- and 15-year survival outcomes was constructed combining age, prostate-specific antigen (PSA), histological grade, biopsy core involvement, stage, and primary treatment, which were each independent prognostic factors for PCSM, and age and comorbidity, which were prognostic for NPCM. The model demonstrated good discrimination, with a C-index of 0.84 (95% CI: 0.82-0.86) and 0.84 (95% CI: 0.80-0.87) for 15-year PCSM in the UK and Singapore validation cohorts, respectively, comparing favourably to international risk-stratification criteria. Discrimination was maintained for overall mortality, with C-index 0.77 (95% CI: 0.75-0.78) and 0.76 (95% CI: 0.73-0.78). The model was well calibrated with no significant difference between predicted and observed PCa-specific (p = 0.19) or overall deaths (p = 0.43) in the UK cohort. Key study limitations were a relatively small external validation cohort, an inability to account for delayed changes to treatment beyond 12 months, and an absence of tumour-stage subclassifications.

Conclusions: 'PREDICT Prostate' is an individualised multivariable PCa prognostic model built from baseline diagnostic information and the first to our knowledge that models potential treatment benefits on overall survival. Prognostic power is high despite using only routinely collected clinicopathological information.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Models, Theoretical*
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prognosis
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / epidemiology*
  • Prostatic Neoplasms / therapy
  • Registries / standards
  • Reproducibility of Results
  • Risk Factors
  • United Kingdom / epidemiology

Grant support

This work was supported by The Urology Foundation Research Scholarship (DRT), www.theurologyfoundation.org, and by The Evelyn Trust (REF 16/16) Cambridge (DRT, PDP, and VJG), http://evelyntrust.com. Infrastructure support was received from Cancer Research UK Cambridge Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The researchers are independent of the sponsors.