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

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.

Reasons for Discontinuing Active Surveillance: Assessment of 21 Centres in 12 Countries in the Movember GAP3 Consortium.

BACKGROUND: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa). OBJECTIVE: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation. DESIGN, SETTING, AND PARTICIPANTS: We compared data from 10296 men on AS from 21 centres across 12 countries. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation. RESULTS AND LIMITATIONS: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4-28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0-13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5-2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4-2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5yr, 4561 had follow-up for <5yr, and 149 were lost to follow-up. Cumulative incidence of progression was 27.5% (95% CI: 26.4-28.6%) at 5yr and 38.2% (95% CI: 36.7-39.9%) at 10yr. A limitation is that not all centres were included due to limited information on the reason for discontinuation and limited follow-up. CONCLUSIONS: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression. PATIENT SUMMARY: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS.