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The long-term outcomes of Gleason grade groups 2 and 3 prostate cancer managed by active surveillance: Results from a large, population-based cohort.

ABSTRACT: INTRODUCTION:Active surveillance (AS) is an accepted management strategy for low-risk prostate cancer (PCa), but its role in the management of favorable intermediate-risk PCa remains controversial. Most reports studying the role of AS for these men generally lack long-term followup and include small numbers of patients. Our objective was to report the outcomes of men diagnosed with Gleason grade groups (GGG) 2 and 3 PCa who were managed expectantly. METHODS:Using administrative datasets and pathology reports, we identified all men who were diagnosed with GGG 2 and 3 PCa and managed expectantly between 2002 and 2011 in Ontario, Canada. Outcomes and associated factors were estimated using cumulative incidence function methods and multivariable Cox regression models, respectively. RESULTS:We identified 926 men who were managed expectantly (AS [n=374] or watchful waiting [n=552]). The eight-year cancer-specific survival was 94% and 89% for the AS and watchful waiting cohorts, respectively. Among AS men, 266 (71%) received treatment after a followup of approximately eight years. Cumulative AS discontinuation rates at one and five years were 30.5% and 65.1%, respectively. CONCLUSIONS:Expectant management of GGG 2 and 3 PCa may be an option for certain men. Notably for AS patients, the cancer-specific mortality at eight years was 6%, and over 65% of men underwent treatment within five years. Further studies are required to evaluate which patients, based on disease-specific features and competing health risks, would benefit most from a conservative strategy.

SUBMITTER: Richard PO

PROVIDER: S-EPMC7654679 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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The long-term outcomes of Gleason grade groups 2 and 3 prostate cancer managed by active surveillance: Results from a large, population-based cohort.

Richard Patrick O PO Timilshina Narhari N Komisarenko Maria M Martin Lisa L Ahmad Ardalan A Alibhai Shabbir M H SMH Hamilton Robert J RJ Kulkarni Girish S GS Finelli Antonio A

Canadian Urological Association journal = Journal de l'Association des urologues du Canada 20200601 6

<h4>Introduction</h4>Active surveillance (AS) is an accepted management strategy for low-risk prostate cancer (PCa), but its role in the management of favorable intermediate-risk PCa remains controversial. Most reports studying the role of AS for these men generally lack long-term followup and include small numbers of patients. Our objective was to report the outcomes of men diagnosed with Gleason grade groups (GGG) 2 and 3 PCa who were managed expectantly.<h4>Methods</h4>Using administrative da ...[more]

PMID: 31977306

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Project description:To determine the role that magnetic resonance (MR) imaging and MR spectroscopic imaging findings obtained at the time of diagnosis play in the progression of disease in patients whose prostate cancer is being managed with active surveillance and to compare the role of these findings with the role of transrectal ultrasonography (US) findings.The institutional review board approved this HIPAA-compliant retrospective study, and informed consent was obtained from all patients whose records were to be entered into the research database. All patients who had prostate cancer managed with active surveillance and who had undergone both MR imaging and MR spectroscopic imaging of the prostate and transrectal US at time of diagnosis were identified. Two urologists blinded to the clinical outcome in these patients independently reviewed and dichotomized the MR imaging report and the MR spectroscopic imaging report as normal or suggestive of malignancy. One experienced urologist performed all US examinations that were then dichotomized similarly. Uni- and multivariate (with use of standard clinical variables) Cox models were fitted to assess time to cancer progression, defined as Gleason score upgrading, prostate-specific antigen velocity of more than 0.75 (microg x L(-1))/y, or initiation of treatment more than 6 months after diagnosis.The final cohort included 114 patients with a median follow-up of 59 months. Patients with a lesion that was suggestive of cancer at MR imaging had a greater risk of the Gleason score being upgraded at subsequent biopsy (hazard ratio, 4.0; 95% confidence interval: 1.1, 14.9) than did patients without such a lesion. Neither MR spectroscopic imaging nor transrectal US could be used to predict cancer progression.Abnormal prostate MR imaging results suggestive of cancer may confer an increased risk of Gleason score upgrade at subsequent biopsy. Although expensive, prostate MR imaging may help in counseling potential candidates about active surveillance.

Project description:ObjectiveTo develop a model and methodology for predicting the risk of Gleason upgrading in patients with prostate cancer on active surveillance (AS) and using the predicted risks to create risk-based personalised biopsy schedules as an alternative to one-size-fits-all schedules (e.g. annually). Furthermore, to assist patients and doctors in making shared decisions on biopsy schedules, by providing them quantitative estimates of the burden and benefit of opting for personalised vs any other schedule in AS. Lastly, to externally validate our model and implement it along with personalised schedules in a ready to use web-application.Patients and methodsRepeat prostate-specific antigen (PSA) measurements, timing and results of previous biopsies, and age at baseline from the world's largest AS study, Prostate Cancer Research International Active Surveillance (PRIAS; 7813 patients, 1134 experienced upgrading). We fitted a Bayesian joint model for time-to-event and longitudinal data to this dataset. We then validated our model externally in the largest six AS cohorts of the Movember Foundation's third Global Action Plan (GAP3) database (>20 000 patients, 27 centres worldwide). Using the model predicted upgrading risks; we scheduled biopsies whenever a patient's upgrading risk was above a certain threshold. To assist patients/doctors in the choice of this threshold, and to compare the resulting personalised schedule with currently practiced schedules, along with the timing and the total number of biopsies (burden) planned, for each schedule we provided them with the time delay expected in detecting upgrading (shorter is better).ResultsThe cause-specific cumulative upgrading risk at the 5-year follow-up was 35% in PRIAS, and at most 50% in the GAP3 cohorts. In the PRIAS-based model, PSA velocity was a stronger predictor of upgrading (hazard ratio [HR] 2.47, 95% confidence interval [CI] 1.93-2.99) than the PSA level (HR 0.99, 95% CI 0.89-1.11). Our model had a moderate area under the receiver operating characteristic curve (0.6-0.7) in the validation cohorts. The prediction error was moderate (0.1-0.2) in theGAP3 cohorts where the impact of the PSA level and velocity on upgrading risk was similar to PRIAS, but large (0.2-0.3) otherwise. Our model required re-calibration of baseline upgrading risk in the validation cohorts. We implemented the validated models and the methodology for personalised schedules in a web-application (http://tiny.cc/biopsy).ConclusionsWe successfully developed and validated a model for predicting upgrading risk, and providing risk-based personalised biopsy decisions in AS of prostate cancer. Personalised prostate biopsies are a novel alternative to fixed one-size-fits-all schedules, which may help to reduce unnecessary prostate biopsies, while maintaining cancer control. The model and schedules made available via a web-application enable shared decision-making on biopsy schedules by comparing fixed and personalised schedules on total biopsies and expected time delay in detecting upgrading.

Dataset Information

The long-term outcomes of Gleason grade groups 2 and 3 prostate cancer managed by active surveillance: Results from a large, population-based cohort.

Publications

The long-term outcomes of Gleason grade groups 2 and 3 prostate cancer managed by active surveillance: Results from a large, population-based cohort.

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