Timo F W Soeterik1, Harm H E van Melick2, Lea M Dijksman3, Douwe H Biesma3, J Alfred Witjes4, Jean-Paul A van Basten5. 1. Santeon Hospital Group, Utrecht, The Netherlands. Electronic address: t.soeterik@antoniusziekenhuis.nl. 2. Department of Urology, St. Antonius Hospital, Nieuwegein-Utrecht, The Netherlands. 3. Department of Value Based Healthcare, St. Antonius Hospital, Nieuwegein-Utrecht, The Netherlands. 4. Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 5. Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
Abstract
BACKGROUND: In 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. OBJECTIVE: To compare AS outcomes for higher-risk patients and very low-risk patients in a large cohort of patients diagnosed with PCa. DESIGN, SETTING, AND PARTICIPANTS: Patients diagnosed with PCa between 2008 and 2015 with clinical stage ≥T1c and managed with AS at six large teaching hospitals. INTERVENTION: AS 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 ANALYSIS: Using 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 LIMITATIONS: Of 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). CONCLUSIONS: In 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 SUMMARY: A 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.
BACKGROUND: In 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. OBJECTIVE: To compare AS outcomes for higher-risk patients and very low-risk patients in a large cohort of patients diagnosed with PCa. DESIGN, SETTING, AND PARTICIPANTS: Patients diagnosed with PCa between 2008 and 2015 with clinical stage ≥T1c and managed with AS at six large teaching hospitals. INTERVENTION: AS 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 ANALYSIS: Using 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 LIMITATIONS: Of 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). CONCLUSIONS: In 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 SUMMARY: A 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.