In this issueThe effect of limited (tertiary) Gleason pattern 5 on the new prostate cancer grade groups☆
Introduction
Traditionally, the risk of recurrence for prostatic adenocarcinoma after prostatectomy, as detected by prostate-specific antigen or other modalities, is based primarily on Gleason score but also on pathologic tumor stage and surgical margin status. Even with the recent modifications of Gleason patterns and the total Gleason score assessment [1], the risk stratification schema most commonly used clinically is based on the distinction between Gleason scores 6 and 7 and 8-10. Recent multi-institutional data spanning the last decade (comprised >20 000 patients from 5 major academic medical institutions) have supported modification of how risk of recurrence is stratified based on the grade groups for prostatic adenocarcinoma of grade group 1 (3 + 3 = 6), grade group 2 (3 + 4 = 7), grade group 3 (4 + 3 = 7), grade group 4 (4 + 4 = 8.3 + 5 = 8.5 + 3 = 8), and grade group 5 (Gleason scores 9-10) [2], [3], [4]. Salient features of the proposed schema favoring adaptation over conventional approaches include the following:
- 1.
A better characterization of the heterogeneity of the risk of recurrence with Gleason score 7, in which 4 + 3 = 7 carries a 5-year risk of recurrence of 30% to 35%, whereas 3 + 4 = 7 exhibits a 5-year risk of recurrence of only 5% to 10%.
- 2.
A better characterization of the heterogeneity of the risk of recurrence in Gleason scores 8-10, in which Gleason scores 9-10 carry a 5-year risk of recurrence of greater than 75%, whereas Gleason score 8 exhibits a significantly decreased 5-year risk of recurrence of 40% to 50%.
- 3.
A better characterization of the uniformly indolent behavior of lesions with only Gleason pattern 3, which exhibit no metastatic potential with a 5-year recurrence risk of less than 3%, all of which are effectively due to local recurrence [5], [6].
Another feature of the proposed Gleason grade group schema is its characterization of the spectrum of the percentage of Gleason pattern 4 that can be seen in a background of Gleason pattern 3: the percent of Gleason pattern 4 in grade group 1 is zero, that in grade group 2 is less than 50%, that in grade group 3 is greater than 50%, and Gleason score 4 + 4 = 8 (grade group 4) is entirely Gleason pattern 4. The proposed grade group 5 can be thought of as the presence of Gleason pattern 5 in the absence of any significant Gleason pattern 3. The importance of tertiary Gleason pattern 5 in prostatectomies was first proposed by our group in 2000 with follow-up studies in 2004 and 2009 in which we documented that the presence of tertiary Gleason pattern generally is associated with higher-stage disease and imparts a worse post-prostatectomy prognosis [7], [8], [9]. Most of prior studies on tertiary patterns used the pre-2005 grading criteria for prostate adenocarcinoma, which varies significantly compared with contemporary prostate cancer grading. Using currently accepted grading definitions of grade patterns and grading rules, the current study seeks to characterize precisely how the introduction of a limited (<5%) Gleason pattern 5 component at prostatectomy affects prognosis and how tertiary patterns fit into the grade group schema and reporting.
Section snippets
Materials and methods
The data from the Johns Hopkins cohort encompassed 9686 patients with paired biopsy and prostatectomy specimens from 2004 to 2014. Of these patients, 5483 had adequate postprostatectomy follow-up (median time of 3 years) along with complete documentation of primary, secondary, and any limited (<5%) Gleason pattern 5 at prostatectomy. The data from the University of Pittsburgh cohort encompassed 2123 patients with adequate follow-up (median follow-up time of 3.9 years) along with complete
The effect of limited Gleason pattern 5 at prostatectomy on BRFS is most pronounced in the context of Gleason score 4 + 4 = 8 and intermediate in the context of Gleason score 7
The aggregate data from 2 independent major academic medical centers comprising 7606 patient records are presented in Fig. 1A. Cases with less than 5% Gleason pattern 5 have been characterized separately from Fig. 1A in Fig. 1B-D. The BRFS across the proposed grade groups is shown in Fig. 1A in which all curves are significantly distinct from one another (log-rank P < .0001, all comparisons). The hazard ratios relative to Gleason score 3 + 3 = 6 with no other Gleason patterns present (grade group 1)
Discussion
The use of the term tertiary in the context of Gleason scores 3 + 3 = 6 and 4 + 4 = 8 is a misnomer in the context of reporting at prostatectomy, as there are only 2 grades present. Gleason score 3 + 3 = 6 with tertiary Gleason pattern 4 is in fact composed of only 2 Gleason patterns, mostly pattern 3 with less than 5% pattern 4. The proposed grade group schema already addresses this issue in that such cases would be included in grade group 2, with an understanding that this is the lower end of the
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Cited by (27)
Prostate Cancer: Update on Grading and Reporting
2022, Surgical Pathology ClinicsCitation Excerpt :Therefore, in a prostatectomy, a tumor nodule composed predominantly of Gleason patterns 3 and 4 with less than 5% Gleason pattern 5 is designated as Gleason score 3 + 4 = 7 or 4 + 3 = 7 with a minor tertiary pattern 5; the GG is based on the Gleason score and not affected by the minor tertiary pattern 5. Available data9 suggest that reporting minor tertiary pattern 5 essentially fine-tunes the prognostic power of the Gleason system such that a GG2 tumor with minor tertiary pattern 5 has a prognosis intermediate between GG2 and GG3, and a GG3 tumor with minor tertiary pattern 5 has a prognosis intermediate between GG3 and GG4. Cribriform prostate cancer has recently emerged to be a Gleason pattern 4 subpattern that connotes adverse clinical outcomes.
Practice patterns related to prostate cancer grading: results of a 2019 Genitourinary Pathology Society clinician survey
2021, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :In RP with Grade Groups 2–3, a “tertiary grade” refers to a third, least common component of pattern 5. Most studies have used a 5% cutoff, while others use a higher/no cut-off (i.e., tertiary = Third most common of any amount) [15–17]. Whereas 78% of GUPS pathologists defined “tertiary” as <5% [3], only half of clinicians presumed this was the case.
The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer
2020, European Urology FocusNeoplasms of the Prostate
2020, Urologic Surgical PathologyControversial issues in Gleason and International Society of Urological Pathology (ISUP) prostate cancer grading: proposed recommendations for international implementation
2019, PathologyCitation Excerpt :Further research needs to be undertaken before a method of handling non-minor tertiary patterns in radical prostatectomies can be fully endorsed. There have been some recent studies suggesting that the integration of minor (so-called tertiary) patterns into ISUP grade can improve the accuracy of predicting PSA recurrence following radical prostatectomy.42–44 However, for the time being, the presence of a minor component of pattern 5 in a Gleason score 7 case should not affect the assignment of ISUP grade.
New prostate cancer grade grouping system predicts survival after radical prostatectomy
2018, Human PathologyCitation Excerpt :In addition to being a retrospective analysis, other weaknesses of our study include lack of thorough PSA data for BRFS analysis and the lack of information on the tertiary Gleason pattern in RP specimens. A recent study has evaluated how the existence of tertiary higher-grade pattern along with the new GG affects the prognosis after RP [32]. Also, as the biopsies are now more often taken under MRI-TRUS fusion guidance, the issues of undersampling can be better avoided [24].
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Disclosures: The authors have no conflict of interest or funding disclosures.