Preoperative Chemoradiotherapy and Transanal Endoscopic Microsurgery Versus Ttransanal Endoscopic Microsurgery in T1 N0, M0 Rectal Cancer (TAUTEM-T1 Study)

Официальное название

Prospective, Controlled and Randomized Phase III Multicentric Study of the Treatment of T1,N0,M0 Rectal Cancer. Neoadjuvant Therapy and Transanal Endoscopic Surgery vs. Transanal Endoscopic Surgery (TAUTEM-T1 Study)

Обзор

Introduction: The standard treatment for rectal adenocarcinoma is total mesorectal excision (TME), a technique involving resection of the rectum, with or without a temporary or permanent stoma. TME is associated with high morbidity and genitourinary alterations. On the other hand, transanal endoscopic surgery (TEM) allows access to tumors up to 20 cm from the anal margin, with much lower postoperative morbidity and without the need for ostomy. For T1, N0, M0 rectal adenocarcinomas without poor prognostic factors, TEM is the technique of choice. However, recent studies have described local recurrences of up to 20%. Our group, TAUTEM, has just completed a phase III clinical trial in T2-T3ab, N0, M0 rectal cancer, comparing preoperative chemoradiotherapy (CRT) and TEM versus TME, with very positive results in terms of postoperative morbidity, quality of life, and a local recurrence rate of 7.4%, not inferior to TME. These results encourage our TAUTEM group to launch a similar project at the T1, N0, M0 stage, comparing standard TEM treatment versus QRT and TEM, aiming to improve rectal preservation outcomes and enhance results regarding local recurrence, distant recurrence, and oncologic survival. Method: Prospective, controlled, randomized phase III multicenter clinical trial. Patients with rectal adenocarcinoma within 10 cm of the anal margin and up to 4 cm in size, staged as T1, N0, M0, will be included. These patients will be randomized into two groups: TEM after CRT and TEM alone. Postoperative morbidity and mortality, CRT side effects, and quality of life will be recorded. The minimum follow-up will evaluate rectal preservation and local recurrence and survival at two and three years. The sample size calculation for the study will be 106 patients. Conclusions: The aim of the study is to improve oncological outcomes in stage T1, N0, M0 rectal cancer through preoperative chemoradiotherapy associated with local surgery (TEM).

Вмешательства

• Препарат Capecitabine (Xeloda)
  Capecitabine 825 mg/m2 every 12 hours orally on days of radiotherapy
• Лучевая терапия 50.4 Gy
  Radiotherapy was administered in daily fractions of 1.8 Gy 5 days a week according to standard schema. The total dose is 45 Gy plus a boost of 5.4 Gy to the tumor area
• Процедура Transanal Endoscopic Microsurgery (TEM)
  10 weeks after Chemoradiotherapy
• Процедура Transanal Endoscopic Microsurgery
  Standard surgical treatment of T1, N0, M0 rectal cancer. Early after diagnosis

Первичные конечные точки

• Rectal preservation in T1,N0,M0 rectal cancer [Срок оценки: 2 years]
• Total mesorectal excision in T1,N0,M0 rectal cancer [Срок оценки: 2 years]

Вторичные конечные точки (6)

• Analysis of tolerance and side effects of preoperative chemoradiotherapy (CRT). [Срок оценки: 30 days after preoperative CRT]
• Postoperative morbidity and mortality in both groups. [Срок оценки: 30 days after surgery]
• The clinical and pathological response of patients undergoing CRT. [Срок оценки: 30 days after surgery]
• Quality of life one year after surgery. [Срок оценки: One year after surgery]
• Local recurrence in both groups [Срок оценки: At two years]
• 3-year survival results in both groups, [Срок оценки: Three years]

Критерии участия

Критерии включения

• Indication by multidisciplinary committee of indication for local excision, according to ESMO and NCCN criteria.
• Rectal adenocarcinomas in the biopsy, located at a distance from the anal margin less than or equal to 10 cm measured by rigid rectoscopy at the time of ER.
• Preoperative staging by ER and pelvic MRI of T1,N0. In case of disparity, higher staging will be considered the definitive diagnosis. If it is greater than T1, it will be excluded.
• Tumors equal to or less than 4 cm in maximum diameter measured by MRI.
• ASA index equal to or less than III.
• Absence of distant metastases by abdominal CT and chest X-ray (if inconclusive, Thoracic CT)

Критерии исключения

• Preoperative staging by EER or pelvic MRI higher than T1 or N0.
• Presence of distant metastases. Synchrony with other colorectal adenocarcinomas.
• Undifferentiated rectal adenocarcinomas or with the presence of poor prognostic factors in the preoperative biopsy (undifferentiated, venous, lymphatic or perineural infiltration, budding) .
• Patients with intolerance to preoperative chemotherapy or radiotherapy.
• Do not sign informed consent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Serra-Aracil X, Pericay C, Badia-Closa J, Golda T, Biondo S, Hernandez P, Targarona E, Borda-Arrizabalaga N, Reina A, Delgado S, Vallribera F, Caro A, Gallego-Plazas J, Pascual M, Alvarez-Laso C, Guadalajara-Labajo HG, Mora-Lopez L. Short-term outcomes of chemoradiotherapy and local excision versus total mesorectal excision in T2-T3ab,N0,M0 rectal cancer: a multicentre randomised, controlled, phas PMID 36220461
• Serra-Aracil X, Pericay C. Reply to the Letter to the Editor 'The role of chemoradiotherapy in organ preservation for rectal cancer' by L. Xie, Q. Chen, and J. Zhu. Ann Oncol. 2023 Apr;34(4):440-442. doi: 10.1016/j.annonc.2022.12.011. No abstract available. PMID 37061250
• Casalots A, Serra-Aracil X, Mora-Lopez L, Garcia-Nalda A, Pericay C, Ferreres JC, Navarro-Soto S. T1 Rectal Adenocarcinoma: a Different Way to Measure Tumoral Invasion Based on the Healthy Residual Submucosa with Its Prognosis and Therapeutic Implications. J Gastrointest Surg. 2021 Oct;25(10):2660-2667. doi: 10.1007/s11605-021-04948-9. Epub 2021 Feb 24. PMID 33629231
• Serra-Aracil X, Pericay C, Golda T, Mora L, Targarona E, Delgado S, Reina A, Vallribera F, Enriquez-Navascues JM, Serra-Pla S, Garcia-Pacheco JC; TAU-TEM study group. Non-inferiority multicenter prospective randomized controlled study of rectal cancer T2-T3s (superficial) N0, M0 undergoing neoadjuvant treatment and local excision (TEM) vs total mesorectal excision (TME). Int J Colorectal Dis. 2018 PMID 29234923
• Naik DN, Kaneda T. Biosynthesis of branched long-chain fatty acids by species of Bacillus: relative activity of three alpha-keto acid substrates and factors affecting chain length. Can J Microbiol. 1974 Dec;20(12):1701-8. doi: 10.1139/m74-263. No abstract available. PMID 4155346
• Serra-Aracil X, Nonell A, Gener-Jorge C, Pericay C, Golda T, Kreisler E, Espin-Basany E, Pallisera A, Badia-Closa J, Espina B, Borda-Arrizabalaga N, Reina A, Guadalajara-Labajo H, Otero A, Delgado S, Kraft M, Querol R, Flor B, Pellino G, Biondo S, Caro-Tarrago A; TAUTEM-T1 collaborative group. Chemoradiotherapy and transanal endoscopic surgery versus transanal endoscopic surgery alone in T1N0M0 re PMID 42026347

Идентификаторы

NCT: NCT06450574 · TAUTEM-T1_2024-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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