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New scoring system to distinguish deep invasive submucosal and muscularis propria colorectal cancer during colonoscopy: a development and global multicenter external validation study (e-T2 Score)

      Background and Aims

      Diagnostics to differentiate deep submucosal invasive (invasion depth ≥1000 μm [T1b]) colorectal cancer (CRC) from muscularis propria invasive (T2) CRC are limited. We aimed to establish and validate a scoring system that differentiates T1b from T2.

      Methods

      A multicenter retrospective cross-validation study was performed. Four hundred sixty-one consecutive pathologically confirmed T1b or T2 CRCs were divided into the development (T1b, 222; T2, 189) and internal validation (T1b, 31; T2, 19) cohorts. Eight potential endoscopic findings were evaluated using the development cohort: loss of lobulation, deep depression, demarcated depressed area, protuberance within the depression, expanding appearance, fold convergency, erosion or white plaque, and Borrmann type 2 or 3 tumor. A scoring system that differentiates T1b from T2 was developed, and diagnostic performance was tested using the internal validation cohort by 8 endoscopists. External validation was conducted using 50 CRC images by 4 endoscopists from other institutions, including outside of Japan.

      Results

      Multivariate analysis identified the following 5 independent predictive endoscopic findings of T2 CRC: deep depression (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.07-4.04), demarcated depressed area (OR, 4.40; 95% CI, 1.39-13.9), 4-fold convergency or more (OR, 3.41; 95% CI, 1.90-6.11), erosion or white plaque (OR, 8.28; 95% CI, 2.77-24.7), and Borrmann type 2 or 3 tumor (OR, 8.76; 95% CI, 3.58-21.5). The area under the receiver-operating characteristic curve (AUROC) was .90 (95% CI, .87-.93) in the development cohort, .80 (95% CI, .76-.85) in the internal validation, and .76 (95% CI, .69-.83) in the external validation.

      Conclusions

      We established and validated a new scoring system to differentiate T1b from T2 CRC using 5 simple endoscopic findings.

      Abbreviations:

      AUROC (Area under receiver operating characteristic curve), CRC (colorectal cancer), ESD (endoscopic submucosal dissection), LNM (lymph node metastasis), NCCH (National Cancer Center Hospital), MRI (magnetic resonance imaging), ROC (receiver operating characteristic), T1 (submucosal invasive), T1a (invasion depth <1000 μm), T1b (invasion depth ≥1000 μm), T2 (muscularis propria invasive)
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      References

        • Saito Y.
        • Uraoka T.
        • Yamaguchi Y.
        • et al.
        A prospective, multicenter study of 1111 colorectal endoscopic submucosal dissections (with video).
        Gastrointest Endosc. 2010; 72: 1217-1225
        • Yamada M.
        • Saito Y.
        • Takamaru H.
        • et al.
        Long-term clinical outcomes of endoscopic submucosal dissection for colorectal neoplasms in 423 cases: a retrospective study.
        Endoscopy. 2017; 49: 233-242
        • Sakamoto T.
        • Saito Y.
        • Nakamura F.
        • et al.
        Short-term outcomes following endoscopic submucosal dissection of large protruding colorectal neoplasms.
        Endoscopy. 2018; 50: 606-612
        • Yoshida N.
        • Naito Y.
        • Inada Y.
        • et al.
        Cross-national analysis about the difference of histopathological management in Tis and T1 colorectal cancer between Japan and Korea.
        J Anus Rectum Colon. 2019; 3: 18-26
        • Bordet M.
        • Bretagne J.F.
        • Piette C.
        • et al.
        Reappraisal of the characteristics, management, and prognosis of intramucosal colorectal cancers and their comparison with T1 carcinomas.
        Gastrointest Endosc. 2021; 93: 477-485
        • Bosch S.L.
        • Teerenstra S.
        • de Wilt J.H.
        • et al.
        Predicting lymph node metastasis in pT1 colorectal cancer: a systematic review of risk factors providing rationale for therapy decisions.
        Endoscopy. 2013; 45: 827-834
        • Wada H.
        • Shiozawa M.
        • Katayama K.
        • et al.
        Systematic review and meta-analysis of histopathological predictive factors for lymph node metastasis in T1 colorectal cancer.
        J Gastroenterol. 2015; 50: 727-734
        • Kitajima K.
        • Fujimori T.
        • Fujii S.
        • et al.
        Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study.
        J Gastroenterol. 2004; 39: 534-543
        • Ueno H.
        • Mochizuki H.
        • Hashiguchi Y.
        • et al.
        Risk factors for an adverse outcome in early invasive colorectal carcinoma.
        Gastroenterology. 2004; 127: 385-394
        • Yoda Y.
        • Ikematsu H.
        • Matsuda T.
        • et al.
        A large-scale multicenter study of long-term outcomes after endoscopic resection for submucosal invasive colorectal cancer.
        Endoscopy. 2013; 45: 718-724
        • Ikematsu H.
        • Yoda Y.
        • Matsuda T.
        • et al.
        Long-term outcomes after resection for submucosal invasive colorectal cancers.
        Gastroenterology. 2013; 144: 551-559
        • Kawachi H.
        • Eishi Y.
        • Ueno H.
        • et al.
        A three-tier classification system based on the depth of submucosal invasion and budding/sprouting can improve the treatment strategy for T1 colorectal cancer: a retrospective multicenter study.
        Mod Pathol. 2015; 28: 872-879
        • Watanabe T.
        • Muro K.
        • Ajioka Y.
        • et al.
        Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer.
        Int J Clin Oncol. 2018; 23: 1-34
        • Tanaka S.
        • Haruma K.
        • Oh E.H.
        • et al.
        Conditions of curability after endoscopic resection for colorectal carcinoma with submucosally massive invasion.
        Oncol Rep. 2000; 7: 783-788
        • Nakadoi K.
        • Tanaka S.
        • Kanao H.
        • et al.
        Management of T1 colorectal carcinoma with special reference to criteria for curative endoscopic resection.
        J Gastroenterol Hepatol. 2012; 27: 1057-1062
        • Oka S.
        • Tanaka S.
        • Nakadoi K.
        • et al.
        Risk analysis of submucosal invasive rectal carcinomas for lymph node metastasis to expand indication criteria for endoscopic resection.
        Dig Endosc. 2013; 25: 21-25
        • Miyachi H.
        • Kudo S.E.
        • Ichimasa K.
        • et al.
        Management of T1 colorectal cancers after endoscopic treatment based on the risk stratification of lymph node metastasis.
        J Gastroenterol Hepatol. 2016; 31: 1126-1132
        • Vermeer N.C.A.
        • Backes Y.
        • Snijders H.S.
        • et al.
        National cohort study on postoperative risks after surgery for submucosal invasive colorectal cancer.
        BJS Open. 2019; 3: 210-217
        • Tanaka S.
        • Asayama N.
        • Shigita K.
        • et al.
        Towards safer and appropriate application of endoscopic submucosal dissection for T1 colorectal carcinoma as total excisional biopsy: future perspectives.
        Dig Endosc. 2015; 27: 216-222
        • Watanabe D.
        • Toyonaga T.
        • Ooi M.
        • et al.
        Clinical outcomes of deep invasive submucosal colorectal cancer after ESD.
        Surg Endosc. 2018; 32: 2123-2130
        • Huh J.W.
        • Kim H.R.
        • Kim Y.J.
        Lymphovascular or perineural invasion may predict lymph node metastasis in patients with T1 and T2 colorectal cancer.
        J Gastrointest Surg. 2010; 14: 1074-1080
        • Fields A.C.
        • Lu P.
        • Hu F.
        • et al.
        Lymph node positivity in T1/T2 rectal cancer: a word of caution in an era of increased incidence and changing biology for rectal cancer.
        J Gastrointest Surg. 2021; 25: 1029-1035
        • Participants in the Paris Workshop
        The Paris endoscopic classification of superficial neoplastic lesions: esophagus, stomach, and colon: November 30 to December 1, 2002.
        Gastrointest Endosc. 2003; 58: S3-43
        • Endoscopic Classification Review Group
        Update on the Paris classification of superficial neoplastic lesions in the digestive tract.
        Endoscopy. 2005; 37: 570-578
        • Kijima S.
        • Sasaki T.
        • Nagata K.
        • et al.
        Preoperative evaluation of colorectal cancer using CT colonography, MRI, and PET/CT.
        World J Gastroenterol. 2014; 20: 16964-16975
        • Malmstrom M.L.
        • Saftoiu A.
        • Vilmann P.
        • et al.
        Endoscopic ultrasound for staging of colonic cancer proximal to the rectum: a systematic review and meta-analysis.
        Endosc Ultrasound. 2016; 5: 307-314
        • Moons K.G.
        • Altman D.G.
        • Reitsma J.B.
        • et al.
        Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration.
        Ann Intern Med. 2015; 162: W1-73
        • Matsuda T.
        • Fujii T.
        • Saito Y.
        • et al.
        Efficacy of the invasive/non-invasive pattern by magnifying chromoendoscopy to estimate the depth of invasion of early colorectal neoplasms.
        Am J Gastroenterol. 2008; 103: 2700-2706
        • Ikehara H.
        • Saito Y.
        • Matsuda T.
        • et al.
        Diagnosis of depth of invasion for early colorectal cancer using magnifying colonoscopy.
        J Gastroenterol Hepatol. 2010; 25: 905-912
        • Yasue C.
        • Chino A.
        • Takamatsu M.
        • et al.
        Pathological risk factors and predictive endoscopic factors for lymph node metastasis of T1 colorectal cancer: a single-center study of 846 lesions.
        J Gastroenterol. 2019; 54: 708-717
        • Kundel H.L.
        • Polansky M.
        Measurement of observer agreement.
        Radiology. 2003; 228: 303-308
        • Utano K.
        • Endo K.
        • Togashi K.
        • et al.
        Preoperative T staging of colorectal cancer by CT colonography.
        Dis Colon Rectum. 2008; 51: 875-881
        • Chan B.P.H.
        • Patel R.
        • Mbuagbaw L.
        • et al.
        EUS versus magnetic resonance imaging in staging rectal adenocarcinoma: a diagnostic test accuracy meta-analysis.
        Gastrointest Endosc. 2019; 90: 196-203
        • Saitoh Y.
        • Obara T.
        • Watari J.
        • et al.
        Invasion depth diagnosis of depressed type early colorectal cancers by combined use of videoendoscopy and chromoendoscopy.
        Gastrointest Endosc. 1998; 48: 362-370
        • Horie H.
        • Togashi K.
        • Kawamura Y.J.
        • et al.
        Colonoscopic stigmata of 1 mm or deeper submucosal invasion in colorectal cancer.
        Dis Colon Rectum. 2008; 51: 1529-1534
        • Mukae M.
        • Kobayashi K.
        • Sada M.
        • et al.
        Diagnostic performance of EUS for evaluating the invasion depth of early colorectal cancers.
        Gastrointest Endosc. 2015; 81: 682-690
        • Inoki K.
        • Sakamoto T.
        • Takamaru H.
        • et al.
        The diagnostic performance for colorectal neoplasms using magnified endoscopy differs between experts and novice endoscopists: a post hoc analysis.
        Digestion. 2020; 101: 590-597
        • Ichimasa K.
        • Kudo S.E.
        • Mori Y.
        • et al.
        Artificial intelligence may help in predicting the need for additional surgery after endoscopic resection of T1 colorectal cancer.
        Endoscopy. 2018; 50: 230-240
        • Kudo S.E.
        • Ichimasa K.
        • Villard B.
        • et al.
        Artificial intelligence system to determine risk of T1 colorectal cancer metastasis to lymph node.
        Gastroenterology. 2021; 160: 1075-1084
        • Weiser M.R.
        AJCC 8th edition: colorectal cancer.
        Ann Surg Oncol. 2018; 25: 1454-1455
        • Japanese Society for Cancer of the Colon and Rectum
        Japanese classification of colorectal, appendiceal, and anal carcinoma: the 3rd English edition [secondary publication].
        J Anus Rectum Colon. 2019; 3: 175-195
        • Rödel C.
        • Graeven U.
        • Fietkau R.
        • et al.
        Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial.
        Lancet Oncol. 2015; 16: 979-989
        • Li Y.
        • Wang J.
        • Ma X.
        • et al.
        A review of neoadjuvant chemoradiotherapy for locally advanced rectal cancer.
        Int J Biol Sci. 2016; 12: 1022-1031