Elsevier

European Urology

Volume 77, Issue 6, June 2020, Pages 675-682
European Urology

Platinum Priority – Prostate Cancer
Editorial by XXX on pp. x–y of this issue
Active Surveillance of Grade Group 1 Prostate Cancer: Long-term Outcomes from a Large Prospective Cohort

https://doi.org/10.1016/j.eururo.2019.12.017Get rights and content

Abstract

Background

Active surveillance (AS) is the preferred management option for most men with grade group (GG) 1 prostate cancer (PCa). Questions persist regarding long-term outcomes and the optimal approach to AS.

Objective

To determine survival and metastatic outcomes in AS patients. Secondary objectives were to measure the cumulative incidence and association of patient-level factors on biopsy grade reclassification.

Design, setting, and participants

A prospective, active, open-enrollment cohort study was conducted from 1995 through July 2018 at a tertiary-care academic institution. Patients with very-low-risk or low-risk PCa were enrolled.

Intervention

AS with semiannual prostate-specific antigen (PSA) and digital rectal examination, serial prostate biopsy, and multiparametric magnetic resonance imaging (mpMRI).

Outcome measurements and statistical analysis

The 10- and 15-yr cumulative incidences of primary and secondary outcomes were determined.

Results and limitations

Overall, 1818 men were monitored on AS for a median of 5.0 yr (interquartile range 2.0–9.0). There were 88 non-PCa deaths, four PCa deaths, and one additional case of metastasis. The cumulative incidence of PCa-specific mortality or metastasis was 0.1% (95% confidence interval, 0.04–0.6%) at both 10 and 15 yr. The 5-, 10-, and 15-yr cumulative incidences of biopsy grade reclassification were 21%, 30%, and 32%, respectively. On multivariable analysis, biopsy grade reclassification was associated with older age, African-American race, PSA density, and increased cancer volume on biopsy, and men who underwent mpMRI prior to enrollment were less likely to undergo grade reclassification. Our selection and monitoring are more stringent than many other contemporary AS programs.

Conclusions

In a large, single-institution, prospective AS cohort, the risk of cancer death or metastasis was <1% over long-term follow-up. Consistent with clinical guidelines, these data support the use of AS for the management of most men diagnosed with GG1 PCa.

Patient summary

This study investigated long-term outcomes in patients with grade group 1 prostate cancer managed with active surveillance (AS). Ten years after enrolling in AS, the risk of metastasis or death from prostate cancer was <1%, while 48% of men switched to treatment. Patients who underwent multiparametric magnetic resonance imaging (mpMRI)/ultrasound-fusion targeted biopsy prior to enrollment were less likely to experience biopsy grade reclassification during follow-up, suggesting a role for mpMRI as part of a comprehensive risk assessment to confirm AS eligibility. These findings support the safety of AS in most men with grade group 1 prostate cancer, but specific outcomes may differ in programs with less intensive monitoring.

Introduction

Active surveillance (AS) is the preferred management strategy for most men with grade group (GG) 1 prostate cancer (PCa) [1]. One concern surrounding AS has been the loss of a window of curability during the course of monitoring [2]. Over the past 2 decades, however, longitudinal data from several institutions have demonstrated the overall safety of AS, with 5- and 10-yr cancer-specific survival rates consistently exceeding 94% [3], [4], [5], [6], [7]. These findings have led to widespread acceptance of AS and its endorsement in clinical guidelines [8].

Nonetheless, many important questions persist regarding AS. First, data are limited regarding the durability of AS beyond 10 yr [2], [3]. Second, the impact of patient-level demographic factors on outcomes remains unclear [1]. Moreover, serial prostate biopsies central to surveillance protocols [3], [4] are associated with significant risks [9], and the role of multiparametric magnetic resonance imaging (mpMRI) as an alternative to biopsy is unclear [2]. We herein report outcomes from a large, prospective AS program with long-term follow-up, including our initial experience using mpMRI.

Section snippets

Prospectively defined AS program

The Johns Hopkins AS program was initiated in 1995 as an option for men with very-low-risk (VLR) PCa [10], defined as clinical stage T1c, prostate-specific antigen (PSA) density (PSAD) <0.15 ng/ml, GG1, two or fewer positive biopsy cores, and ≤50% cancer involvement of any biopsy core [11]. Over time, an increasing number of patients were enrolled with low-risk (LR; clinical stage ≤T2a, PSA <10 ng/ml, and GG1) cancer (Supplementary Fig. 1).

All men were recommended to undergo follow-up biopsy

Study cohort

From January 1995 through June 2018, 1818 men with VLR and LR PCa were enrolled in AS (Table 1). The median follow-up for men at risk of upgrading was 5.0 yr (interquartile range [IQR] 2.0–9.0), and the median interval between biopsies was 13 mo (IQR 12–15). In total, 920 men had ≥5 yr of follow-up and 305 had ≥10 yr of follow-up. The cumulative incidences of ongoing cancer assessment (defined as: PSA, mpMRI, and/or prostate biopsy within 18 mo) at 3, 5, and 10 yr after diagnosis were 94%, 88%, and

Discussion

AS is a widely accepted management option for men with GG1 PCa [1], [2], [8], but questions persist regarding long-term outcomes and the optimal approach to patient selection and monitoring [2], [3], [4]. Consistent with previous findings [4], the current analysis revealed 10- and 15-yr cumulative incidences of PCSM or metastasis to be <1%. Accordingly, we observed a 22-fold increased risk of dying from non-PCa causes than from PCa at the end of the overall study period. On multivariable

Conclusions

These data support the safety of AS as a guideline-endorsed, first-line management approach in most men with GG1 PCa. Patients should be counseled with regard to their personal preferences and informed of the limitations of currently available data. With additional follow-up of our cohort and others, optimal use of mpMRI and other technologies will be better defined, and the approach to AS will continue to evolve toward a sufficiently thorough, less invasive ideal.


Author contributions: Mufaddal

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These authors contributed equally to this report.

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