Endoscopic Versus Surgical Treatment for T1 Colorectal Cancer

Colorectal Cancer Clinical Trial

— EpiT1  

Official title:

Endoscopic Versus Surgical Treatment for T1 Colorectal Cancer: a Population-based Cohort Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04150081
• Other study ID #: HCB/2019/0224
• Status: Active, not recruiting
• Start date: November 1, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: March 2022
• Source: Hospital Clinic of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The implementation of population screening programs for colorectal cancer (CRC) has led to a considerable increase in the prevalence T1 CRC originating on polyps amenable by endoscopy. The benefits of secondary oncological surgery in terms of disease free survival are not well established.

Hypothesis: The characteristics of the individuals and the polyp (endoscopic, histological) should allow us to discriminate T1 CRCs that may benefit from secondary surgery from those that only require local treatment. With the current criteria, the management of patients with T1 CRC is suboptimal since a high proportion of patients are refered for unnecessary surgeries without a clear benefit in terms of survival. Molecular signatures can help to discriminate those patients with good prognosis that do not require secondary surgery nor cancer related follow up.

Description:

The primary objective of the study is to compare the effect of oncological surgery versus local treatment for the management of polyps with T1 CRC in relation to disease-free survival and morbi-mortality of the therapeutic procedure. We will also validate molecular signatures in endoscopic samples for the prediction of lymph node metastasis and survival. Methodology: Clinical Study: Retrospective population-based cohort study that will include baseline clinical and follow up data of more than 1400 T1 CRCs in at least 10 Spanish autonomous communities from 2007 to 2017. A centralized pathological review will be carried out by a group of expert pathologists. Inter and intraobserver variability for histological staging will be assessed. A predictive model will be created to discriminate individuals with high probability of receiving surgical and local treatment. For those patients who have a similar probability range, the results in progression-free survival and adverse events will be compared. Translational phase: A 5miRNAs and 8mRNA signature predictive of lymph node metastasis will be assessed in 200 endoscopic samples and related with prognosis.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1400
• Est. completion date: December 31, 2022
• Est. primary completion date: May 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• All patients diagnosed with pT1 CRC will be included, regardless of endoscopic features, treatment received and lymph node staging

Exclusion Criteria:

• CRC with other histology than adenocarcinoma

• Patients with hereditary syndromes of CRC (Lynch syndrome, classical familial adenomatous polyposis) or inflammatory bowel disease.

• Synchronous CRC

• Metachronous CRC in the previous 5 years

• Patients with metastatic neoplastic disease at the time of diagnosis

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Procedure:
• Surgery or Endoscopic treatment
All the patients in the cohort will receive surgery o local (endoscopic) treatment, in some cases additional surgical treatment will be performed after an endoscopic primary treatment. This decision will have been taken based on daily clinical practice and does not represent a study intervention.

Locations

Country	Name	City	State
Spain	María Pellisé. MD. PhD.	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona	Fundacion Clinic per a la Recerca Biomédica

Country where clinical trial is conducted

Spain, 

References & Publications (16)

Backes Y, de Vos Tot Nederveen Cappel WH, van Bergeijk J, Ter Borg F, Schwartz MP, Spanier BWM, Geesing JMJ, Kessels K, Kerkhof M, Groen JN, Wolfhagen FHJ, Seerden TCJ, van Lelyveld N, Offerhaus GJA, Siersema PD, Lacle MM, Moons LMG. Risk for Incomplete Resection after Macroscopic Radical Endoscopic Resection of T1 Colorectal Cancer: A Multicenter Cohort Study. Am J Gastroenterol. 2017 May;112(5):785-796. doi: 10.1038/ajg.2017.58. Epub 2017 Mar 21. — View Citation

Beaton C, Twine CP, Williams GL, Radcliffe AG. Systematic review and meta-analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer. Colorectal Dis. 2013 Jul;15(7):788-97. doi: 10.1111/codi.12129. Review. — View Citation

Belderbos TD, van Erning FN, de Hingh IH, van Oijen MG, Lemmens VE, Siersema PD. Long-term Recurrence-free Survival After Standard Endoscopic Resection Versus Surgical Resection of Submucosal Invasive Colorectal Cancer: A Population-based Study. Clin Gastroenterol Hepatol. 2017 Mar;15(3):403-411.e1. doi: 10.1016/j.cgh.2016.08.041. Epub 2016 Sep 5. — View Citation

Benson AB, Venook AP, Al-Hawary MM, Cederquist L, Chen YJ, Ciombor KK, Cohen S, Cooper HS, Deming D, Engstrom PF, Garrido-Laguna I, Grem JL, Grothey A, Hochster HS, Hoffe S, Hunt S, Kamel A, Kirilcuk N, Krishnamurthi S, Messersmith WA, Meyerhardt J, Miller ED, Mulcahy MF, Murphy JD, Nurkin S, Saltz L, Sharma S, Shibata D, Skibber JM, Sofocleous CT, Stoffel EM, Stotsky-Himelfarb E, Willett CG, Wuthrick E, Gregory KM, Freedman-Cass DA. NCCN Guidelines Insights: Colon Cancer, Version 2.2018. J Natl Compr Canc Netw. 2018 Apr;16(4):359-369. doi: 10.6004/jnccn.2018.0021. — View Citation

Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, Arnold D; ESMO Guidelines Committee. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv22-iv40. doi: 10.1093/annonc/mdx224. Erratum in: Ann Oncol. 2018 Oct 1;29(Suppl 4):iv263. — View Citation

Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T, Hasegawa K, Hotta K, Ishida H, Ishiguro M, Ishihara S, Kanemitsu Y, Kinugasa Y, Murofushi K, Nakajima TE, Oka S, Tanaka T, Taniguchi H, Tsuji A, Uehara K, Ueno H, Yamanaka T, Yamazaki K, Yoshida M, Yoshino T, Itabashi M, Sakamaki K, Sano K, Shimada Y, Tanaka S, Uetake H, Yamaguchi S, Yamaguchi N, Kobayashi H, Matsuda K, Kotake K, Sugihara K; Japanese Society for Cancer of the Colon and Rectum. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020 Jan;25(1):1-42. doi: 10.1007/s10147-019-01485-z. Epub 2019 Jun 15. — View Citation

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Logan RF, Patnick J, Nickerson C, Coleman L, Rutter MD, von Wagner C; English Bowel Cancer Screening Evaluation Committee. Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests. Gut. 2012 Oct;61(10):1439-46. Epub 2011 Dec 7. — View Citation

Lopez A, Bouvier AM, Jooste V, Cottet V, Romain G, Faivre J, Manfredi S, Lepage C. Outcomes following polypectomy for malignant colorectal polyps are similar to those following surgery in the general population. Gut. 2019 Jan;68(1):111-117. doi: 10.1136/gutjnl-2016-312093. Epub 2017 Oct 26. — View Citation

Oka S, Tanaka S, Saito Y, Iishi H, Kudo SE, Ikematsu H, Igarashi M, Saitoh Y, Inoue Y, Kobayashi K, Hisabe T, Tsuruta O, Sano Y, Yamano H, Shimizu S, Yahagi N, Watanabe T, Nakamura H, Fujii T, Ishikawa H, Sugihara K; Colorectal Endoscopic Resection Standardization Implementation Working Group of the Japanese Society for Cancer of the Colon and Rectum, Tokyo, Japan. Local recurrence after endoscopic resection for large colorectal neoplasia: a multicenter prospective study in Japan. Am J Gastroenterol. 2015 May;110(5):697-707. doi: 10.1038/ajg.2015.96. Epub 2015 Apr 7. — View Citation

Overwater A, Kessels K, Elias SG, Backes Y, Spanier BWM, Seerden TCJ, Pullens HJM, de Vos Tot Nederveen Cappel WH, van den Blink A, Offerhaus GJA, van Bergeijk J, Kerkhof M, Geesing JMJ, Groen JN, van Lelyveld N, Ter Borg F, Wolfhagen F, Siersema PD, Lacle MM, Moons LMG; Dutch T1 CRC Working Group. Endoscopic resection of high-risk T1 colorectal carcinoma prior to surgical resection has no adverse effect on long-term outcomes. Gut. 2018 Feb;67(2):284-290. doi: 10.1136/gutjnl-2015-310961. Epub 2016 Nov 3. — View Citation

Ozawa T, Kandimalla R, Gao F, Nozawa H, Hata K, Nagata H, Okada S, Izumi D, Baba H, Fleshman J, Wang X, Watanabe T, Goel A. A MicroRNA Signature Associated With Metastasis of T1 Colorectal Cancers to Lymph Nodes. Gastroenterology. 2018 Mar;154(4):844-848.e7. doi: 10.1053/j.gastro.2017.11.275. Epub 2017 Dec 2. — View Citation

Richards CH, Ventham NT, Mansouri D, Wilson M, Ramsay G, Mackay CD, Parnaby CN, Smith D, On J, Speake D, McFarlane G, Neo YN, Aitken E, Forrest C, Knight K, McKay A, Nair H, Mulholland C, Robertson JH, Carey FA, Steele R; Scottish Surgical Research Group. An evidence-based treatment algorithm for colorectal polyp cancers: results from the Scottish Screen-detected Polyp Cancer Study (SSPoCS). Gut. 2018 Feb;67(2):299-306. doi: 10.1136/gutjnl-2016-312201. Epub 2016 Oct 27. — View Citation

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Yoda Y, Ikematsu H, Matsuda T, Yamaguchi Y, Hotta K, Kobayashi N, Fujii T, Oono Y, Sakamoto T, Nakajima T, Takao M, Shinohara T, Fujimori T, Kaneko K, Saito Y. A large-scale multicenter study of long-term outcomes after endoscopic resection for submucosal invasive colorectal cancer. Endoscopy. 2013 Sep;45(9):718-24. doi: 10.1055/s-0033-1344234. Epub 2013 Aug 5. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Evaluate the effect of surgery and local (endoscopic) treatment on overall survival (expressed in months)	1 year
Primary	Disease free survival	Evaluate the effect of surgery and local (endoscopic) treatment on disease free survival (expressed in months)	1 year
Primary	Develop a predictive model of the probability of receiving surgical treatment	Determine factors associated with the choice of primary treatment and final treatment (endoscopic, primary surgery or secondary surgery) and to develop a predictive model that allow discriminate individuals with high probability of receiving surgical treatment	1 year
Primary	Validation of molecular signatures	Evaluate the validity of molecular signatures based on mRNA and miRNA (determined in endoscopic samples) for prediction lymph node metastasis	2 years
Secondary	Prognosis	Determine the prognosis of patients with pT1CRC in relation to the treatment received (local, primary surgery or secondary surgery)	1 year
Secondary	Risk of lymph node metastasis	Evaluate the factors of the individual and the polyp that are associated with lymph node metastasis	1 year
Secondary	Concordance of histological evaluation	Evaluate the inter-intraexplorer concordance of the pathologists for the histological staging criteria.	2 years
Secondary	T1 CRC in screening program	Compare the characteristics of the T1 CRCs diagnosed within a population screening program and outside it.	1 year
Secondary	Proportion of adverse events	Evaluate the proportion of adverse effects after endoscopic or surgical treatment	1 year
Secondary	Sensitivity and specificity of follow-up tests	To evaluate the performances of the different tests (CT, US, blood markers, colonoscopy) during follow up for detecting recurrence	1 year