A Global, Integrated, Personalized, Stage-related, Multimodal Therapeutic Approach for Rectal Adenocarcinoma Based on Organ Sparing and Mininvasivity (INTERPRETE)

Fondazione del Piemonte per l'Oncologia

Status: Enrolling

Conditions: Rectal Adenocarcinoma; Non Metastatic

Treatments: Procedure: experimental chemoradiotherapy; Procedure: Sparing Approach; Procedure: Standard Chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT06952101

001-FPO24

Details and patient eligibility

About

A phase II, single-center, non-profit, interventional study on patients affected by rectal adenocarcinoma. Patients will be stratified into three groups based on pre-treatment clinical stage. The study investigates and may propose a comprehensive, stage-specific, multimodal approach to rectal adenocarcinoma, with a focus on organ preservation even in early stages (cT1-2N0). When organ-sparing strategies are not feasible, the approach prioritizes minimally invasive techniques (laparoscopic and robotic) to reduce the physical, psychological, and quality-of-life impact on patients.

Full description

Patients affected by rectal adenocarcinoma will be stratified into three groups according to pre-treatment clinical stage:

Group 1: pT1cN0M0 tumors may be candidates for Endoscopic Resection (ER), Local Excision (LE), or TransAnal Minimally Invasive Surgery (TAMIS). If final pathology classifies these tumors as "high-risk" pT1, patients are typically candidates for radical rectal resection due to an estimated 20% risk of mesorectal lymph node metastases. However, many patients refuse surgery and opt for direct follow-up despite the increased risk of recurrence. The investigators propose an alternative treatment with experimental chemoradiotherapy (spCRT) to reduce the risk of local relapse in patients unwilling to undergo surgery, followed by an intensive surveillance protocol. Accurate staging with pelvic MRI, CT scan, and whole-body PET must be performed prior to local excision to exclude false-positive mesorectal lymph nodes. A subsequent Watch and Wait (W&S) strategy may be considered.

Group 2: cT2N0 tumors are typically managed with upfront surgical rectal resection. This study proposes an alternative approach based on spCRT. Literature indicates that the rate of pathological Complete Response (pCR) after CRT is significantly higher than the 25% typically reported for intermediate to advanced rectal tumors. Clinical Complete Response (cCR) or clinical Minimal Residual disease (cMR) will be assessed through multidisciplinary, high-resolution restaging including pelvic MRI, whole-body PET, thoraco-abdominal CT scan, EndoRectal Ultrasound (ERUS), and rectoscopy. In patients achieving cCR or cMR, a W&S approach or LE/TAMIS may be proposed to minimize the psychological and physical burden of surgery, with subsequent close surveillance.

Group 3: Patients with cT3-4, N+, circumferential resection margin positive (CRM+), or extramural vascular invasion (EMVI+) tumors will initially receive standard chemoradiotherapy (stCRT). Those who achieve cCR or cMR at restaging may be considered for organ-sparing approaches (W&S/LE/TAMIS) according to established multicenter research protocols.

All patients in Group 1 and Group 2 who do not achieve cCR or cMR will be managed according to the principle of minimal invasiveness. These patients will undergo laparoscopic or robotic rectal resection with preservation of pelvic autonomic nerves, aimed at reducing genitourinary dysfunction and improving short-term outcomes (e.g., reduced postoperative pain, fewer abdominal wall hernias, faster bowel function recovery, and quicker return to daily activities). Recovery will be further optimized through integration with Enhanced Recovery After Surgery (ERAS) protocols.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients aged ≥18 yrs old
• Patients able to sign the informed consent
• Patients with High Risk pT1 rectal adenocarcinoma endoscopically excised
• Patients with cT2-3aN0 rectal adenocarcinoma who has complete/major response to EXPERIMENTAL CRT
• Patients with cT3b4N0-1 rectal adenocarcinoma who has complete/major response to STANDARD CRT

Exclusion criteria

• cT2-4 any NM0 who don't reach cCR or cMR after experimental/standard CRT
• Pregnancy

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 3 patient groups

Sparing Approach

Experimental group

Description:

Group 1 - Patients with high-risk pT1cN0M0 cancerized adenoma, diagnosed through histological analysis following Endoscopic Resection (ER) or Local Excision (LE). For patients classified as "high-risk" pT1 at final pathology, an experimental sparing strategy is proposed, consisting of experimental chemoradiotherapy (spCRT) followed by a Watch and Wait (W\&W) approach (also referred to as Organ-Sparing Approach, OSA), in selected cases.

Treatment:

Procedure: Sparing Approach

Experimental Chemoradiotherapy: A Path to Conservative Treatment

Experimental group

Description:

Group 2 - Patients with cT2N0 tumors, typically candidates for upfront radical rectal resection. An alternative, non-operative approach is proposed based on experimental chemoradiotherapy (spCRT). According to current literature, the pathologic Complete Response (pCR) rate following CRT significantly exceeds the 25% commonly reported for intermediate to advanced rectal tumors. Clinical Complete Response (cCR) or clinical Minimal Residual disease (cMR) will be assessed through multidisciplinary, high-resolution restaging, including: Pelvic Magnetic Resonance Imaging (MRI) Positron Emission Tomography (PET) Thoraco-abdominal Computed Tomography (CT) Endorectal Ultrasound (ERUS) Rectoscopy In patients achieving cCR or cMR, a Watch \& Wait (W\&W) strategy or Local Excision/Transanal Minimally Invasive Surgery (LE/TAMIS) may be proposed to avoid the physical and psychological burden of major surgery. An intensive follow-up protocol will be implemented.

Treatment:

Procedure: experimental chemoradiotherapy

tandard Chemotherapy Approach: Restaging for Conservative Surgery

Active Comparator group

Description:

Group 3 - Patients with cT3-4, N+, CRM-positive, or EMVI-positive tumors will receive standard chemoradiotherapy (stCRT) as the initial treatment. Patients achieving cCR or cMR at restaging will be evaluated for organ-sparing strategies, including Watch \& Wait (W\&W) or LE/TAMIS, in accordance with existing multicenter clinical research protocols. In cases where a conservative approach is not feasible, standard surgical treatment will follow.

Treatment:

Procedure: Standard Chemotherapy