Multidimensional Study Designed to Develop a Methodological Framework Based on MRI Data to Predict Pathological Complete Response (pCR) in Patients With Locally Advanced Rectal Cancer After Neoadjuvant Treatment

Обзор

Rectal cancer presents a significant global health challenge. Despite improvements in clinical outcomes, significant disparities persist across Europe. These differences are explained not only by the heterogeneity of risk factors and screening strategies, but also by variations in diagnostic and therapeutic approaches, which are highly dependent on medical imaging. Standard treatment for locally advanced rectal cancer based on staging MRI is neoadjuvant treatment (NAT), for tumour downsizing and downstaging, followed by total mesorectal excision. In a significant proportion of cases, radical surgery leads to substantial long-term complications like sexual and urinary dysfunction, fecal incontinence, and impairment in daily activities. Given that up to 42% of patients show complete tumor regression at pathology (i.e. pathological complete response pCR), to avoid unnecessary radical surgery, non-operative management has become an attractive alternative when there are no signs of viable tumour after NAT (i.e. clinical complete response cCR). Such patients are candidates for Watch-and-Wait (W\&W), an established active surveillance policy in specialized centers worldwide relying on clinical examination, endoscopy and MRI. On the other hand, W\&W carries a risk of local regrowth (persistence of microscopic residual disease despite apparent cCR). Even in expert hands, assessment of tumor response is not perfect and local regrowth based on current selection methods occurs in \~30% of cases. Although deferred surgery is a successful treatment with no apparent negative impact on local disease control, an increased rate of distant metastases has been recently reported. Therefore, there is a critical unmet clinical need to detect complete responses after NAT and avoid unnecessary surgery with its associated morbidity and quality of life impairment risks, while also improving sensitivity for residual microscopic disease that will result in local regrowth and associated reduced disease-free survival. Rectal cancer poses a burden not only on healthcare systems, but also on patient well-being. Patients frequently suffer from feelings of isolation and helplessness when faced with unpredicted disease-related situations, given the common difficulties to access high quality information and communicate with attending physicians. As such, there is a clear need to unburden healthcare facilities from unnecessary hospital visits, while improving patient outcomes, engagement, support and care.

Вмешательства

• Другое questionnaire completion
  For all patients, questionnaires will be completed: * At the MRI staging if applicable, * At the MRI restaging, * Every 3 months during the first year; and * Every 6 months during the second year. The following validated questionnaires will be used: * EORTC QLQ-C30 (overall quality of life) * EORTC QLQ-CR29 (colorectal cancer-specific symptoms) * EORTC IN-PATSAT32 (patient satisfaction with care)

Первичные конечные точки

• developpement and validation of a methodological framework based on advanced MRI data to predict pathological complete response in patients with locally advanced rectal cancer after neoadjuvant treatment [Срок оценки: From the baseline to the end of follow up, assessed up to 27 months]

Вторичные конечные точки (4)

• evaluation of the overall diagnostic performance of the predictive model. [Срок оценки: From the baseline to the end of follow up, assessed up to 27 months]
• identification and validation of new MRI biomarkers capable of distinguishing residual tumor from benign fibrotic tissue, using ex vivo MRI of surgical specimens with direct correlation to histological data. [Срок оценки: From the baseline to the end of follow up, assessed up to 27 months]
• establishment of a rectal MRI database to support this project and future research. [Срок оценки: From the baseline to the end of follow up, assessed up to 27 months]
• assessment of the impact of the disease and therapeutic strategies on patients' quality of life. [Срок оценки: From the baseline to the end of follow up, assessed up to 27 months]

Критерии участия

Inclusion Criteria for the preclinical phase :

• Age ≥18 years old;
• Have a confirmed diagnosis of locally advanced rectal cancer;
• Have completed neoadjuvant chemoradiotherapy;
• Be a candidate for surgical treatment with total mesorectal excision;
• Be willing and able to provide written informed consent;
• Affiliation to the French Social Security System.

Inclusion criteria for the clinical phase:

• Age ≥18 years old;
• Have a confirmed diagnosis of locally advanced rectal cancer;
• Require neoadjuvant chemoradiotherapy or have completed neoadjuvant chemoradiotherapy;
• Requires either surgical treatment or a non-surgical strategy ("Watch-and-Wait") after neoadjuvant chemoradiotherapy;
• Be willing and able to provide written informed consent;
• Affiliation to the French Social Security System.

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 1 центр

• ICM — Montpellier

Публикации

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• Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010 Sep;11(9 PMID 20692872
• Garcia-Aguilar J, Shi Q, Thomas CR Jr, Chan E, Cataldo P, Marcet J, Medich D, Pigazzi A, Oommen S, Posner MC. A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol. 2012 Feb;19(2):384-91. doi: 10.1245/s10434-011-1933-7. Epub 2011 Jul 14. PMID 21755378
• Park IJ, Yu CS. Current issues in locally advanced colorectal cancer treated by preoperative chemoradiotherapy. World J Gastroenterol. 2014 Feb 28;20(8):2023-9. doi: 10.3748/wjg.v20.i8.2023. PMID 24587677
• Dattani M, Heald RJ, Goussous G, Broadhurst J, Sao Juliao GP, Habr-Gama A, Perez RO, Moran BJ. Oncological and Survival Outcomes in Watch and Wait Patients With a Clinical Complete Response After Neoadjuvant Chemoradiotherapy for Rectal Cancer: A Systematic Review and Pooled Analysis. Ann Surg. 2018 Dec;268(6):955-967. doi: 10.1097/SLA.0000000000002761. PMID 29746338
• Sao Juliao GP, Habr-Gama A, Vailati BB, Perez RO. The good, the bad and the ugly: rectal cancers in the twenty-first century. Tech Coloproctol. 2017 Jul;21(7):573-575. doi: 10.1007/s10151-017-1651-7. Epub 2017 Jun 19. No abstract available. PMID 28631136

Идентификаторы

NCT: NCT07404228 · PROICM 2025-07 RES

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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