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

NCT07404228 | Not Yet Recruiting

• 1 other identifier: PROICM 2025-07 RES
• Study Type: observational
• Target: 115
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mri; Rectal Cancer; Chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• 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

  using the area under the ROC curve (AUC) to distinguish pathological complete response (pCR) from residual disease.

  From the baseline to the end of follow up, assessed up to 27 months

Secondary Outcomes (4)

• evaluation of the overall diagnostic performance of the predictive model.

  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.

  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.

  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.

  From the baseline to the end of follow up, assessed up to 27 months

Study Arms (2)

Phase 1 (Preclinical): An ex-vivo analysis of surgical specimens

15 surgical specimens will be collected after surgery following neoadjuvant treatment. They will be imaged using a 3T MRI with advanced sequences, then returned to the pathology department. This ex vivo MRI will not affect sample preparation or preservation. MRI images will be aligned with histological sections using non-linear registration to compare MRI parameters with digital pathology data. This step will help identify MRI biomarkers that differentiate healthy tissue, post-treatment fibrotic tissue, and residual tumor. We will assess whether diffusion MRI and relaxometry measurements can predict pathological outcomes by analyzing parameters such as fractional anisotropy, mean diffusivity, and kurtosis, using surgical pathological information when available

Phase 2 (Clinical): An in-vivo clinical MRI study.

The same advanced sequences will be added to MRIs performed during routine clinical care: the initial staging MRI before neoadjuvant chemoradiotherapy, the restaging MRI after treatment completion, and follow-up MRIs for patients managed with a non-operative Watch-and-Wait strategy. For each patient, we will collect imaging data, demographics, medical history, tumor characteristics, treatment details, pathology reports, and clinical follow-up (endoscopy and MRI). All data will be pseudonymized. The second phase involves developing a computational model to predict response to neoadjuvant therapy. A machine learning tool will be designed to predict complete pathological response based on quantitative MRI, standard clinical MRI, and clinical information

Other: questionnaire completion

Interventions

questionnaire completion OTHER

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)

Phase 2 (Clinical): An in-vivo clinical MRI study.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Preclinical phase: For patients requiring surgery after neoadjuvant chemoradiotherapy, a surgical consultation will be scheduled as part of routine care. The study will be explained, and an information sheet provided. Participation requires signing the informed consent by the patient and the investigating surgeon. Clinical phase: When a patient requires an MRI as part of their standard care, the study will be presented during the radiology consultation with an information sheet. If the patient agrees to participate, the informed consent form must be signed by the patient and the investigating physician. Patients may be included in the study at two possible times: during the MRI performed before neoadjuvant treatment (MRI staging), or during the re-evaluation MRI after neoadjuvant treatment (MRI restaging).

You may qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Institut du Cancer de Montpellier - Val d'Aurelle: lead

Study Sites (1)

ICM

Montpellier, Herault, 34298, France

Location

Related Publications (15)

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

• Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986 Jun 28;1(8496):1479-82. doi: 10.1016/s0140-6736(86)91510-2.

  PMID: 2425199 BACKGROUND

• Wrenn SM, Cepeda-Benito A, Ramos-Valadez DI, Cataldo PA. Patient Perceptions and Quality of Life After Colon and Rectal Surgery: What Do Patients Really Want? Dis Colon Rectum. 2018 Aug;61(8):971-978. doi: 10.1097/DCR.0000000000001078.

  PMID: 29944576 BACKGROUND

• 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):835-44. doi: 10.1016/S1470-2045(10)70172-8. Epub 2010 Aug 6.

  PMID: 20692872 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Beets-Tan RGH, Lambregts DMJ, Maas M, Bipat S, Barbaro B, Curvo-Semedo L, Fenlon HM, Gollub MJ, Gourtsoyianni S, Halligan S, Hoeffel C, Kim SH, Laghi A, Maier A, Rafaelsen SR, Stoker J, Taylor SA, Torkzad MR, Blomqvist L. Magnetic resonance imaging for clinical management of rectal cancer: Updated recommendations from the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting. Eur Radiol. 2018 Apr;28(4):1465-1475. doi: 10.1007/s00330-017-5026-2. Epub 2017 Oct 17.

  PMID: 29043428 BACKGROUND

• Socha J, Kepka L, Michalski W, Paciorek K, Bujko K. The risk of distant metastases in rectal cancer managed by a watch-and-wait strategy - A systematic review and meta-analysis. Radiother Oncol. 2020 Mar;144:1-6. doi: 10.1016/j.radonc.2019.10.009. Epub 2019 Nov 8.

  PMID: 31710938 BACKGROUND

• van der Valk MJM, Hilling DE, Bastiaannet E, Meershoek-Klein Kranenbarg E, Beets GL, Figueiredo NL, Habr-Gama A, Perez RO, Renehan AG, van de Velde CJH; IWWD Consortium. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet. 2018 Jun 23;391(10139):2537-2545. doi: 10.1016/S0140-6736(18)31078-X.

  PMID: 29976470 BACKGROUND

• Nasir I, Fernandez L, Vieira P, Pares O, Santiago I, Castillo-Martin M, Domingos H, Cunha JF, Carvalho C, Heald RJ, Beets GL, Parvaiz A, Figueiredo N. Salvage surgery for local regrowths in Watch & Wait - Are we harming our patients by deferring the surgery? Eur J Surg Oncol. 2019 Sep;45(9):1559-1566. doi: 10.1016/j.ejso.2019.04.006. Epub 2019 Apr 13.

  PMID: 31006589 BACKGROUND

• Fernandez LM, Sao Juliao GP, Renehan AG, Beets GL, Papoila AL, Vailati BB, Bahadoer RR, Kranenbarg EM, Roodvoets AGH, Figueiredo NL, Van De Velde CJH, Habr-Gama A, Perez RO; International Watch & Wait Database (IWWD) Consortium. The Risk of Distant Metastases in Patients With Clinical Complete Response Managed by Watch and Wait After Neoadjuvant Therapy for Rectal Cancer: The Influence of Local Regrowth in the International Watch and Wait Database. Dis Colon Rectum. 2023 Jan 1;66(1):41-49. doi: 10.1097/DCR.0000000000002494. Epub 2022 Oct 21.

  PMID: 36515514 BACKGROUND

• Smith JJ, Strombom P, Chow OS, Roxburgh CS, Lynn P, Eaton A, Widmar M, Ganesh K, Yaeger R, Cercek A, Weiser MR, Nash GM, Guillem JG, Temple LKF, Chalasani SB, Fuqua JL, Petkovska I, Wu AJ, Reyngold M, Vakiani E, Shia J, Segal NH, Smith JD, Crane C, Gollub MJ, Gonen M, Saltz LB, Garcia-Aguilar J, Paty PB. Assessment of a Watch-and-Wait Strategy for Rectal Cancer in Patients With a Complete Response After Neoadjuvant Therapy. JAMA Oncol. 2019 Apr 1;5(4):e185896. doi: 10.1001/jamaoncol.2018.5896. Epub 2019 Apr 11.

  PMID: 30629084 BACKGROUND

• Tsunoda A, Nakao K, Hiratsuka K, Yasuda N, Shibusawa M, Kusano M. Anxiety, depression and quality of life in colorectal cancer patients. Int J Clin Oncol. 2005 Dec;10(6):411-7. doi: 10.1007/s10147-005-0524-7.

  PMID: 16369745 BACKGROUND

Related Links

• Rectal cancer: ESMO clinical practice guidelines

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Stephanie NOUGARET, PHD

  ICM Co. Ltd.

  STUDY DIRECTOR

Central Study Contacts

Aurore MOUSSION

CONTACT

0467613102; drci-icm105@icm.unicancer.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2026
• First Posted: February 11, 2026
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2029
• Last Updated: June 4, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Access to study data upon written detailed request sent to ICM, from 6 months until 5 years after publication of summary data.
• Access Criteria: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from ICM for personal access, and data will only be transferred after signing of a data access agreement.

Locations

FR (1)