Active Surveillance for Prostate Cancer in a Real-life Cohort: Comparing Outcomes for PRIAS-eligible and PRIAS-ineligible Patients

Abstract

BackgroundIn daily practice, a wider range of patients with prostate cancer (PCa) are selected for active surveillance (AS) compared to those in AS trials, including higher-risk patients. However, less is known about the outcomes for off-protocol selected PCa patients who opt for AS. ObjectiveTo compare AS outcomes for higher-risk patients and very low-risk patients in a large cohort of patients diagnosed with PCa. Design, setting, and participantsPatients diagnosed with PCa between 2008 and 2015 with clinical stage ≥T1c and managed with AS at six large teaching hospitals. InterventionAS included regular prostate-specific antigen (PSA) testing (every 3–6 mo) and a confirmatory biopsy 1 yr after diagnosis and every 3 yr thereafter. Outcomes measurements and statistical analysisUsing the inclusion criteria of the PRIAS study, outcomes for PRIAS-eligible patients (ie, cT1c–T2, Gleason sum score ≤6, ≤2 positive biopsy cores, PSA ≤10 ng/ml, and PSA density <0.2 ng/ml/ml) were compared to outcomes for PRIAS-ineligible patients. Unfavourable outcomes following deferred surgery, biochemical recurrence, and risk of metastasis were calculated using univariate and multivariate Cox regression analyses. Time to tumour progression was established using survival analysis. Results and limitationsOf the 1000 patients included and managed with AS, almost half of the patients (49%) had higher-risk disease characteristics than the PRIAS inclusion criteria. PRIAS-ineligible patients discontinued AS because of tumour progression significantly earlier than PRIAS-eligible patients (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.44–2.11); they also had a higher risk of positive surgical margins (odds ratio [OR] 2.15, 95% CI 1.11–4.17) and unfavourable pathological findings (OR 3.20, 95% CI 1.61–6.35) following deferred radical prostatectomy. PSA density ≥0.2 ng/ml/ml was the most important individual predictor and, in addition to a higher risk of tumour progression and unfavourable surgical outcomes, was also associated with a significantly higher risk of biochemical progression following deferred radical prostatectomy (OR 3.26, 95% CI 1.23–8.64). In the overall population, PSA density ≥0.2 ng/ml/ml was also associated with a higher risk of metastasis (HR 2.71, 95% CI 1.23–5.96). ConclusionsIn this cohort, approximately half of the patients did not meet the inclusion criteria of the PRIAS study. These patients had a two- to threefold higher risk of disease progression and unfavourable outcomes following deferred prostatectomy. PSA density is an important individual predictor of unfavourable outcomes and should be taken into account when selecting patients for AS. Patient summaryA large proportion of patients with prostate cancer on active surveillance are not in the lowest risk group. These patients have a higher risk of experiencing tumour progression to a stage requiring curative intervention. They also have worse disease prognosis compared to patients on active surveillance in the lowest risk group.