Reducing Overtreatment of Prostate Cancer Patients: Revisiting the European Association of Urology Pretreatment Risk Group Classification Using Long-term Follow-up Data from the European Randomized Study of Screening for Prostate Cancer Rotterdam

Abstract

Background and objective

Tailored treatment for prostate cancer (PCa) requires accurate risk stratification. This study examines the effectiveness of the European Association of Urology (EAU) classification in predicting long-term PCa-specific mortality (PCSM) and assesses whether an alternative system can improve the identification of patients with low-risk disease.

Methods

This study included two cohorts of patients with localized PCa: one with screen-detected PCa (n = 1563; S-cohort) and the other with clinically detected PCa (n = 755; C-cohort), all from a population-based, randomized screening study, who underwent primary radical prostatectomy or radiation monotherapy. Patients were stratified according to the traditional EAU risk classification and an alternative risk classification where low-risk disease is adjusted according to contemporary active surveillance (AS) eligibility criteria. The 15-yr time-dependent area under the curve (AUC) and the cumulative incidence of PCSM at 15 yr after diagnosis were assessed for each risk classification and cohort.

Key findings and limitations

With a median follow-up of 20 yr in the S-cohort and 12 yr in the C-cohort, the EAU classification demonstrated 15-yr AUCs of 0.76 (95% confidence interval [CI]: 0.71–0.80) and 0.72 (95% CI: 0.65–0.79), respectively, for predicting PCSM. The alternative classification showed a 15-yr AUC of 0.74 (95% CI: 0.69–0.79) in the S-cohort and 0.75 (95% CI: 0.68–0.81) in the C-cohort. The alternative classification identified 45% more men having a low risk in the S-cohort and 83% more in the C-cohort than the EAU classification, with no statistically significant increase in the 15-yr PCSM incidence (S-cohort subhazard ratio: 1.33 [95% CI: 0.66–2.68]; C-cohort subhazard ratio: 0.99 [95% CI: 0.29–3.38]).

Conclusions and clinical implications

The EAU classification predicts PCSM accurately, but an alternative classification, adjusted for AS eligibility, identifies substantially more men as having a low risk. This could enhance AS acceptance and utilization in clinical practice, reducing overtreatment.

Patient summary

This study shows that while a commonly used pretreatment risk classification for prostate cancer predict disease prognosis accurately, an alternative system based on active surveillance eligibility criteria identifies many more men as having a low risk. Adopting this classification could enhance the acceptance and use of active surveillance, reducing unnecessary treatments.