Discordance in TME specimen grading in a Prospective Rectal Cancer Trial: Are we Overestimating the Quality of our Resections ?
Patricia Sylla*1, Mariana Berho13, Alexandros Polydorides14, Alison Ricardo1, Antoinette Bonaccorso1, Erin Moshier15, Riva Letchinger2, John Marks3, Mark Whiteford4, Elizabeth Mclemore5, Justin Maykel6, Karim Alavi6, Jennifer Davids6, Karen Zaghiyan7, Sami Chadi8, Sherief Shawki9, Scott Steele10, Alessio Pigazzi11, Matt Albert12, Teresa Debeche Adams12, Steven D. Wexner2
1Surgery, Mount Sinai Hospital, New York, NY; 2Surgery, Cleveland Clinic Florida, Fort Lauderdale, FL; 3Surgery, Lankenau Medical Center, Philadelphia, PA; 4Surgery, Providence Medical Center, Providence, OR; 5Surgery, Kaiser Permanente, Los Angeles, CA; 6Surgery, U Mass Memorial Hospital, Wochester, MA; 7Surgery, Cedar Sinai Hospital, Los Angeles, CA; 8Surgery, University Health Network, Toronto, ON, Canada; 9Surgery, Mayo Clinic, Rochester, MN; 10Surgery, Cleveland Clinic, Cleveland, OH; 11Surgery, Weill Medical College, New York, NY; 12Surgery, Advent Health, Orlando, FL; 13Pathology, Cleveland Clinic Florida, Fort Lauderdale, FL; 14Pathology, Mount Sinai Hospital, New York, NY; 15Department of Preventive Medicine, Mount Sinai Hospital, New Yorl, NY
Objectives: Grading of total mesorectal excision (TME) specimen is based on macroscopic assessment of the mesorectum and standardized through synoptic pathology reporting. TME grade is a strong predictor of outcomes with incomplete (IC) TME associated with increased local recurrence relative to complete or near complete (C/NC) TME. Although TME grade is used as a primary endpoint in most rectal cancer surgical trials, it is rarely prospectively audited for accuracy. In protocols incorporating centralized blinded review of TME specimens, discordance in grading has not been evaluated. We report the results of a rigorous quality control (QC) process in the grading of TME specimens during a multicenter prospective rectal cancer trial (NCT03144765).
Methods: A phase II prospective trial evaluating the safety and efficacy of transanal TME (taTME) for stage I-III rectal cancer was conducted from 2015-2022 across 11 North American centers. The primary endpoint was TME quality based on standardized TME grading. QC included (1) mandatory training of site pathologists in TME protocols and grading prior to site initiation, (2) secondary blinded review and grading of de-identified TME specimen photographs by centralized pathologists to assess concordance (complete agreement in TME grade), minor (C vs NC or NC vs C) and major discordance (C/NC vs IC or IC vs C/NC) in grading, (3) reconciliation of major discordance by re-review of specimen photographs prior to trial reporting. Cohen’s Kappa statistic was used to assess agreement between site and centralized pathologists grading.
Results: 100 patients underwent sphincter-preserving taTME for tumors located a median 5.8 (range 2.0-9.0;IQR 4.5-7.0) cm from the anal verge. Overall agreement between site and central reviewer grading was rated as fair, (κ = 0.35 (95% CI, 0.10 to 0.61) p<0.0001). Concordance was noted in 53%, with minor and major discordance recorded in 33% and 14% of cases respectively. Upon reconciliation, 13/14 (93%) of cases with major discordance were resolved by site pathologists agreeing to downgrade (8/14, 57%) or upgrade (1/14, 7%), or by central reviewers agreeing to upgrade (3/14, 22%) or downgrade (1/14, 7%) their grading. Reconciliation could not be achieved in 1/14 (7%) case. Pre- vs post-reconciliation rates of C/NC and IC TME are 78%/15% and 7% vs 70%/20% and 10%. Reconciliation resulted in a major upgrade (IC to NC, N=1) or major downgrade (C or NC to IC, N=4) in 5 cases overall (5%).
Conclusions: TME grading was largely concordant between site and central reviewers, however a 14% rate of major discordance was observed. Resolution of discordances resulted in major upgrading or downgrading of the final TME grade in 5% of cases, which suggests that reported rates or TME completeness are likely overestimated in rectal cancer trials. Quality control through secondary review of TME specimen photographs by blinded pathologists with reconciliation of major discordances is strongly recommended.
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