Elsevier

European Urology

Volume 71, Issue 5, May 2017, Pages 750-759
European Urology

Platinum Priority – Prostate Cancer
Application of a Prognostic Gleason Grade Grouping System to Assess Distant Prostate Cancer Outcomes

https://doi.org/10.1016/j.eururo.2016.11.032Get rights and content

Abstract

Background

There is growing enthusiasm for the adoption of a novel grade grouping system to better represent Gleason scores.

Objective

To evaluate the ability of prognostic Gleason grade groups to predict prostate cancer (PCa)–specific mortality (PCSM) and bone metastatic progression.

Design, setting, and participants

We identified patients with PCa enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry across treatment strategies, including conservative and nondefinitive therapy.

Outcome measurements and statistical analysis

We examined the prognostic ability of Gleason grade groups to predict risk of PCSM and bone metastasis using the Kaplan-Meier method and unadjusted and adjusted Cox proportional hazards models.

Results and limitations

We identified 10 529 men with PCa followed for a median of 81 mo (interquartile range 40–127), including 64% in group I (< 3 + 4); 17% in group II (3+4); 9% in group III (4+3); 6% in group IV (4+4); and 4% in group V (≥ 4 + 5). Relative to grade group I, the unadjusted risks of PCSM and bone metastasis were significantly associated with prognostic grade groupings for both biopsy and prostatectomy samples (all p < 0.01). Pairwise comparisons within Gleason sums collapsed within grade group V were not significant; however, this analysis was limited by a small representation of men with Gleason pattern ≥ 4 + 5.

Conclusions

The prognostic grade grouping system is associated with risk of PCSM and metastasis across management strategies, including definitive therapy, conservative management, and primary androgen deprivation.

Patient summary

A five-level reporting system for prostate cancer pathology is associated with the risk of late prostate cancer endpoints.

Introduction

Conceived five decades ago, the Gleason scoring system is a clinical variable strongly associated with prostate cancer (PCa) outcome [1]. With time, incremental modifications to the standards for pathologic reporting have allowed for greater agreement between biopsy and radical prostatectomy (RP) specimens, yet have resulted in the elimination of nearly half of the initially proposed Gleason scores (ie, sums 2–5) [2], [3], [4]. A well-recognized communication challenge has emerged whereby the lowest assigned Gleason sum associated with PCa is reported as 6 on a scale from 2 to 10. As a result, a reduction in the practical histologic spectrum may serve to misrepresent the degree of clinical risk and potentially compound the problem of overtreatment for men with low-grade tumors with a perceived higher than actual risk.

A novel grade grouping system offering five tiers consistent with modern reporting conventions has been proposed, and there has been a groundswell of momentum in support of its widespread adoption, including a recent announcement requiring consistent use for publication in major urologic oncology journals, including European Urology [5], [6]. To date, a number of validation studies examining the ability of this revised Gleason grading reporting system to predict clinical recurrence following definitive therapy have been published, as well as two publications addressing PCa-specific mortality following conservative management and radiotherapy [7], [8], [9], [10], [11], [12]. However, it is unknown if a reporting rubric that collapses the highest Gleason sums (group V) will in turn mask differences in clinical outcome within these subcategories, or whether such a system will perform adequately when broadly implemented outside of academic centers and across treatment types. Therefore, we aimed to evaluate the association of prognostic Gleason grade group with risk of PCa-specific mortality (PCSM) and the development of bone metastasis across management strategies among men in a large multicenter registry.

Section snippets

Patients and methods

Study participants were enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry initiated in 1995, which prospectively tracks clinical characteristics, treatment, relapse, survival, and quality-of-life outcomes for men with PCa [13]. CaPSURE comprises 43 sites, including 36 community-based practices, three academic centers, and four US Veterans Affairs medical centers. The study is managed under institutional review board supervision, with all patients

Results

The primary cohort consisted of 10 529 men whose primary management consisted of RP, EBRT, BT, ADT, or AS/WW. These included 6776 men (64%) in grade group I; 1773 (17%) in group II; 955 (9%) in group III; 636 (6%) in group IV; and 389 (4%) in group V. Men treated with RP were younger (mean age 61.6 yr) than those who underwent BT monotherapy (mean 68.0 yr), EBRT (mean 70.1 yr), primary ADT (73.0), or AS/WW (mean 71.4; p < 0.01. Median follow-up after treatment for patients not experiencing PCSM

Discussion

Comprehensible reporting of PCa histologic grades is likely to have an impact on a disease characterized by diversity in biology, clinical outcomes, management choices, and quality of information [15], [16], [17]. This may be particularly meaningful at the lower end of the spectrum, where high rates of treatment occur among those with Gleason score < 3 + 4 disease [18]. The prospect of removing historical vestiges within the Gleason scale (ie, sums 2–5) has long been advanced as one response to

Conclusions

We confirm that the new Gleason grouping system is associated with distant clinical endpoints across management strategies, including active surveillance, watchful-waiting and non-definitive therapy. No significant distinction in outcome was detected within the Gleason scores combined within the highest Grade grouping, however this represented a small proportion of men within the study cohort.

References (28)

  • J.I. Epstein et al.

    The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma

    Am J Surg Pathol

    (2005)
  • A. Billis et al.

    The impact of the 2005 International Society Of Urological Pathology consensus conference on standard Gleason grading of prostatic carcinoma in needle biopsies

    J Urol

    (2008)
  • H. Uemura et al.

    Usefulness of the 2005 International Society of Urologic Pathology Gleason grading system in prostate biopsy and radical prostatectomy specimens

    BJU Int

    (2009)
  • J.I. Epstein et al.

    The 2014 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system

    Am J Surg Pathol

    (2016)
  • Cited by (37)

    • Pattern of Biopsy Gleason Grade Group 5 (4 + 5 vs 5 + 4 vs 5 + 5) Predicts Survival After Radical Prostatectomy or External Beam Radiation Therapy

      2022, European Urology Focus
      Citation Excerpt :

      It is possible that sample size limitations prevented such comparisons. Similarly, in the CaPSURE-based study investigating the prognostic value of all five grade groups by Leapman et al [19], only seven and 20 patients had Gleason 5 + 5 and Gleason 5 + 4, respectively, in the RP treatment group, with corresponding numbers of eight and 19 patients in the EBRT group. Our study shares similarities in patient distribution with previous studies that addressed similar endpoints.

    • Neoplasms of the Prostate

      2020, Urologic Surgical Pathology
    • Prognostic significance of the presence of intraductal carcinoma of the prostate and bone metastasis in needle biopsy for prostate carcinoma patients with Grade Group 5

      2020, Pathology Research and Practice
      Citation Excerpt :

      Noguchi et al. also found that the number of bone lesions seen on bone scans was significantly associated with CSS of PCa patients [15]. Additionally, the prognostic grade grouping system was associated with risk of metastasis [16]. The aim of this study is to evaluate the prognostic significance of IDC-P and bone metastasis in needle biopsy for Chinese PCa patients with Grade Group 5 disease using OS and CSS as an end point.

    View all citing articles on Scopus
    View full text