Can Neoadjuvant Chemoradiotherapy be Ommited in Mid-rectal Cancer

Официальное название

Can Neoadjuvant Chemoradiotherapy be Omitted in cT2N+ and cT3 Mid-rectal Cancer: A Prospective, Observational Cohort Study

Обзор

This project aims to compare the oncological and functional outcomes of patients with mid-rectal cancer who have a low risk of local recurrence (without MRF involvement) and who either receive or do not receive neoadjuvant chemoradiotherapy (nCRT). Main Question: H0: In mid-rectal cancer patients without MRF involvement (cT2N+ and cT3Nx), there is no difference in 3-year disease-free survival between direct TME and TME after nCRT. H1: In mid-rectal cancer patients without MRF involvement (cT2N+ and cT3Nx), direct TME is associated with worse 3-year disease-free survival compared to TME after nCRT. Participants already taking both interventions as part of their regular medical care for rectal cancer will be recruited in a prospective database for 5 years.

Подробное описание

Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment for patients with locally advanced rectal cancer. This approach has been shown to improve local control and reduce recurrence rates. However, there is no clear evidence showing the advantage of neoadjuvant CRT in high and middle rectal tumors without involvement of mesorectal fascia (MRF). The MERCURY study demonstrated that preoperative MRI-predicted positive CRM is an independent factor for local recurrence. Following this study, the selective use of nCRT in patients at high risk of local recurrence has been proposed.

The ESMO guidelines indicate that T3a/b rectal tumors located above the levator muscles, without involvement of the circumferential resection margin (CRM) or extramural venous invasion (EMVI), are associated with a very low risk of local recurrence. Consequently, they suggest that upfront TME may be an appropriate treatment option for this subgroup of patients. This recommendation remains unchanged in the presence of lymph node involvement within the same group. For clinically staged cT3a/b mid- or high-rectal tumors with clear CRM and no evidence of EMVI, the routine use of nCRT remains a subject of debate. If the surgeon consistently performs high-quality total mesorectal excision (TME), upfront surgery may be a suitable treatment option for this subgroup of patients.

In line with these recommendations, some surgeons perform upfront TME for patients with T2-3 node-positive mid-rectal cancer in the absence of MRF involvement. However, in these cases, the common approach is to administer neoadjuvant chemoradiotherapy. This study seeks to observe whether upfront TME achieves similar 3-year disease-free survival compared to the standard approach of nCRT followed by TME in patients with cT2N+ and cT3Nx mid-rectal cancer without mesorectal fascia involvement.

Вмешательства

• Другое Total mesorectal excision
  Direct surgery without receiving neoadjuvant chemoradiotherapy
• Другое Neoadjuvant Chemotherapy followed by total mesorectal excision
  Neoadjuvant chemoradiotherapy treatment regimens (including conventional chemoradiotherapy/radiotherapy/chemotherapy regimens or total neoadjuvant chemoradiotherapy regimens) before surgery

Первичные конечные точки

• Disease-free survival (DFS) [Срок оценки: 3 years]

Вторичные конечные точки (4)

• Overall Survival [Срок оценки: 3 and 5 years]
• Local Recurrence Rate [Срок оценки: 3 years and 5 years]
• Colorectal Cancer Specific Quality of Life [Срок оценки: Baseline, 1 year, 3 years and 5 years]
• Bowel Dysfunction Related Quality of Life [Срок оценки: Baseline, 1 year, 3 years and 5 years]

Критерии участия

Критерии включения

• Pathologically confirmed rectal cancer
• Rectal cancer within 6-12 cm from anal verge confirmed by sigmoidoscopy or located between the anorectal junction and peritoneal reflection identified by MRI
• Clinical local staging performed by MRI
• cT2N+, cT3N0 and cT3N+ tumors
• Patients without mesorectal fascia involvement assessed by MRI (≤1 mm)
• Patients without pathological (short axis ≥7 mm) lateral (extramesorectal) lymph nodes on MRI
• Patients without EMVI on MRI

Критерии исключения

• cT4 tumors
• Stage IV disease
• Patients with MSI (+) in TME pathology
• PAtients who received neoadjuvant immunotherapy
• Emergency surgery
• Clinical obstruction
• Previous pelvic radiotherapy
• Patients treated without a multidisciplinary council decision
• Inflammatory bowel diseases (Crohn's disease, Ulcerative colitis)
• Familial adenomatous polyposis (FAP), attenuated FAP, and other polyposis syndromes
• Hereditary non-polyposis colorectal cancer (Lynch syndrome)
• Synchronous colon tumors

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Turkey (Türkiye) · 5 центров

• Baskent University — Ankara
• Istanbul Health and Technology University — Istanbul
• Memorial sisli Hospital — Istanbul
• Acibadem Kent Hospital — Izmir
• Dokuz Eylul University — Izmir

Публикации

• Patel UB, Taylor F, Blomqvist L, George C, Evans H, Tekkis P, Quirke P, Sebag-Montefiore D, Moran B, Heald R, Guthrie A, Bees N, Swift I, Pennert K, Brown G. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol. 2011 Oct 1;29(28):3753-60. doi: 10.1200/JCO.2011.34.9068. Epub 2011 Aug 29. PMID 21876084
• Ruppert R, Kube R, Strassburg J, Lewin A, Baral J, Maurer CA, Sauer J, Junginger T, Hermanek P, Merkel S; other members of the OCUM Group. Avoidance of Overtreatment of Rectal Cancer by Selective Chemoradiotherapy: Results of the Optimized Surgery and MRI-Based Multimodal Therapy Trial. J Am Coll Surg. 2020 Oct;231(4):413-425.e2. doi: 10.1016/j.jamcollsurg.2020.06.023. Epub 2020 Jul 19. PMID 32697965
• Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rodel 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. No abstract available. PMID 28881920
• Karakayali F, Arslan C, Bisgin T, Erenler Bayraktar I, Bayraktar O, Canda AE. Can neoadjuvant chemoradiotherapy be omitted in cT2N+ and cT3 mid-rectal cancer: Protocol for a prospective, observational, cohort study (CANO). PLoS One. 2025 Nov 5;20(11):e0321819. doi: 10.1371/journal.pone.0321819. eCollection 2025. PMID 41191581

Идентификаторы

NCT: NCT06823297 · KA24/461

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗