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.

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.

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).

All data will be available after publication of the results in peer-reviewed revues, and in national and international meetings. It includes all de-identified participants' data, the study protocol, the statistical analysis plan and the clinical study report. The corresponding author will provide data and datasets generated and/or analyzed during the study upon reasonable request.

Access to study data upon written detailed request sent to ICM, from 6 months until 5 years after publication of summary data.

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.