Metastatic potential to regional lymph nodes with Gleason score ≤7, including tertiary pattern 5, at radical prostatectomy

Diolombi, Mairo L.; Epstein, Jonathan I.

doi:10.1111/bju.13623

Cited by 10 publications

(22 citation statements)

References 55 publications

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“…This is also supported by the low rate of lymph node metastases in men with GG2 Pca. Diolombi and Epstein [22] found 0.6% pelvic lymph node metastasis among 3235 men with GG2 Pca at RP without stratification for CR/IDC. In another GG2 RP cohort, lymph node metastasis were present in 12/228 (5.3%) patients with CR/IDC but in none of 192 men without CR/IDC [23].…”

Section: Discussionmentioning

confidence: 98%

Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups

et al. 2020

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E U R O P E A N U R O L O G Y 7 7 ( 2 0 2 0 ) 1 9 1 -1 9 8 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Abstract Background: Grade groups (GGs) are an important parameter for therapeutic decision making in prostate cancer (Pca) patients. Invasive cribriform and/or intraductal carcinoma (CR/IDC) has an independent prognostic value for disease outcome, but are not included in the GG limiting their clinical use. Objective: To perform a proof-of-principle study incorporating CR/IDC in the current GG. Design, setting, and participants: All prostate biopsies of 1031 men with screen-detected Pca between 1993 and 2000 were reviewed for the current GG (ranging from 1 to 5) and CR/IDC. The cribriform grade (cGrade) was equal to the GG if CR/IDC was present and GG minus 1 if not. GG1 was cGrade1 if intraductal carcinoma was absent. Intervention: Biopsy review for GG and CR/IDC. A total of 406 patients had received radical prostatectomy (RP), 508 radiotherapy (RT), 108 surveillance, and eight hormonal therapy, and the treatment was unknown for one patient.Outcome measurements and statistical analysis disease-specific survival (DSS), metastasisfree survival (MFS), and biochemical recurrence-free survival (BCRFS) after 15.1 yr (interquartile range 10.9-19.7 yr) follow-up were compared using Harrell's C-statistic. Results and limitations: The biopsy GGs were 486 GG1, 310 GG2, 104 GG3, 64 GG4, and 67 GG5; cGrade distributions were 738 cGrade1, 102 cGrade2, 91 cGrade3, 58 cGrade4, and 42 cGrade5. The cGrade had a better discriminative value than the GG for DSS (C-index 0.79; 95% confidence interval 0.74-0.83 vs 0.76; 0.71-0.82) and MFS (0.79; 0.74-0.84 vs 0.77; 0.72-0.82). The discriminative value for BCRFS after RP and RT was similar for both models. Different diagnostic, such as use of sextant biopsies, and therapeutic strategies in the 1990s are the limitations of this study. Conclusions: The cGrade is a simple Pca grade modification with better discriminative values for DSS and MFS than the GG, particularly impacting decision making in men with current GG2 Pca. Patient summary: Microscopic grading is an important factor for decision making in prostate cancer (Pca) patients. We show that [ 4 5 _ T D $ D I F F ] a simple grade modification better predicts Pca outcome and might improve treatment choices.

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Section: Discussionmentioning

confidence: 98%

Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups

et al. 2020

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“…While the ISUP 2014 report suggested that a TP be defined exclusively as truly minor/limited (,5%) and should not alter the Grade Group, there is conflicting evidence in contemporary cohorts. [9][10][11][12]15,16,18 Importantly, although reporting of TPs is recommended for RP specimens, there is discordance with clinical predictive models that do not include TP in a standard fashion. [23][24][25] This is likely due to the reality that almost all TP studies are single institution reports, may be underpowered to show clear prognostic significance in multivariable analysis, often have short follow-up, and have not yet shown utility in clinical decision-making.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5] While most of so-called tertiary grading reported in the literature refers to a higher grade-typically pattern 5-the term has been used variably regarding extent, ranging from a more limited, minor, or less than 5% highergrade carcinoma component in initial publications 3,4 to a third most common pattern of any percentage. [6][7][8][9][10][11][12][13][14][15][16][17][18] The accepted method for reporting ''tertiary'' patterns also differs between needle biopsy and radical prostatectomy (RP). As codified by the International Society of Urologic Pathology (ISUP) 2005 and 2014 grading conferences, cases with 3 patterns on needle biopsy should be graded by using a ''first plus worst'' (most common þ next highest grade) strategy.…”

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confidence: 99%

“…21,22 For RP specimens bearing 3 grading patterns, since the pathologist may assess the entire tumor, the ''tertiary'' terminology has been recommended. 19 The latter recommendation is based on an array of studies 3,4,[6][7][8][9][10][11][12][13][14][15][16][17][18] showing that cancers with a tertiary higher-grade pattern (TP) are associated with increased stage and/or biochemical recurrence following RP when compared with their closest grading counterpart (eg, 4 þ 3 ¼ 7 with tertiary pattern 5 compared with 4 þ 3 ¼ 7). Paradoxically however, TPs are not routinely incorporated into predictive clinical models.…”

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confidence: 99%

“…Paradoxically however, TPs are not routinely incorporated into predictive clinical models. [23][24][25] While most tertiary grading studies have defined the term as minor/less than 5%, 3,4,[11][12][13][14][15][16][17][18] this is not universal, [6][7][8][9][10]26 and no study has ever documented practice patterns across a range of grading scenarios. Understanding how and when tertiary grades are assigned has become more intriguing with the introduction of a prognostic Grade Group system.…”

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Practice Patterns in Reporting Tertiary Grades at Radical Prostatectomy: Survey of a Large Group of Experienced Urologic Pathologists

Fine

Meisels

Al‐Ahmadie

et al. 2019

Archives of Pathology &Amp; Laboratory Medicine

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Context.— In prostate cancer, “tertiary” higher-grade patterns (TPs) have been associated with biochemical recurrence after radical prostatectomy. Objective.— To determine variation regarding definition and application of TPs. Design.— Online survey regarding TPs in a range of grading scenarios circulated to 105 experienced urologic pathologists. Results.— Among 95 respondents, 40 of 95 (42%) defined TPs as “third most common pattern” and 55 (58%) as “minor pattern/less than 5% of tumor.” In a tumor with pattern 3 and less than 5% pattern 4, of the 95 respondents, 35 (37%) assigned 3 + 3 = 6 with TP4, while 56 (59%) assigned 3 + 4 = 7. In a tumor with pattern 4 and less than 5% pattern 5, of the 95 respondents, 51 (54%) assigned 4 + 4 = 8 with TP5, while 43 (45%) assigned 4 + 5 = 9. Six scenarios were presented in which the order of most common patterns was 3, 4, and 5 (Group 1) or 4, 3, and 5 (Group 2) with varying percentages. In both groups, when pattern 5 was less than 5%, we found that 98% and 93% of respondents would assign 3 + 4 = 7 or 4 + 3 = 7 with TP5. In scenarios with 15% or 25% pattern 5, most respondents (70% and 80%, respectively) would include pattern 5 as the secondary grade, that is, 3 + 5 = 8 (Group 1) or 4 + 5 = 9 (Group 2). For 85 of 95 (89%), a TP would not impact Grade Group assignment. Conclusions.— This survey highlights substantial variation in practice patterns regarding definition and application of “tertiary” grading in radical prostatectomy specimens. High consistency was observed in 3 + 4 = 7/4 + 3 = 7 scenarios with truly minor pattern 5. These findings should inform future studies assessing the standardization and predictive value of “tertiary” patterns.

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Prevalence of adverse pathology features in grade group 2 prostatectomy specimens with syn‐ or metachronous metastatic disease

Downes

Jain

et al. 2021

The Prostate

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Background: To validate the importance of recently established adverse histopathology features (cribriform pattern and intraductal carcinoma) as contraindication for deferred treatment of Gleason score 7 (3 + 4) (grade group [GG] 2) prostate cancer, we investigated their frequency in GG2 radical prostatectomies with syn-or metachronous metastatic disease.Methods: GG2 prostatectomy specimens of patients with concomitant lymph node metastasis or distant metastasis at follow-up were identified in a clinical database of a tertiary care center and their pathology was reviewed for pathological stage, lymphovascular invasion, Gleason grade 4 subpatterns, presence of tertiary grade 5, and ductal adenocarcinoma histology. A control group of 99 GG2 prostatectomy specimens who had no metastatic disease (controls) was reviewed for the same adverse pathological features.Results: Of 1860 GG2 prostatectomy specimens (operated between 2002 and 2020), 45 (2.4%) had concurrent regional lymph node metastases or distant metastases at follow-up. Pathological stage distribution of cases and controls was 24% and 79% pT2, 42% and 15% pT3a, 33% and 6.1% pT3b -T4, respectively (p < 0.001).Eleven of 45 cases (24%) had ≤10% Gleason grade 4 component. Cribriform pattern or intraductal carcinoma was present in 84% of cases versus 34% of controls (p < 0.001), tertiary grade 5 in 16% of cases versus 5% controls (p = 0.05) and ductal adenocarcinoma in 16% of cases versus 2% of controls (p = 0.004). Among the seven cases without cribriform or intraductal carcinoma, two displayed ductal adenocarcinoma features.Conclusions: Well-established unfavorable histopathologic features (intraductal and cribriform pattern carcinoma, ductal adenocarcinoma) are represented in about 90% of GG2 prostate cancers with local or distant metastatic disease and are much less common (38%) in those without metastatic disease. Strikingly, about 25% of GG2 prostatectomy cases with metastatic disease had an organ-confined disease and/or a small percentage of Gleason grade 4 pattern. This further emphasizes the relative

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Metastatic potential to regional lymph nodes with Gleason score ≤7, including tertiary pattern 5, at radical prostatectomy

Cited by 10 publications

References 55 publications

Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups

Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups

Practice Patterns in Reporting Tertiary Grades at Radical Prostatectomy: Survey of a Large Group of Experienced Urologic Pathologists

Prevalence of adverse pathology features in grade group 2 prostatectomy specimens with syn‐ or metachronous metastatic disease

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