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.
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
cT2-4 any NM0 who don't reach cCR or cMR after experimental/standard CRT
Pregnancy
Parallel
Sparing Approach
Procedure/SurgeryAccurate staging with Pelvic MRI, CT scan, PET total body have to be performed before local excision in order to exclude false positive mesorectal lymph nodes. Subsequent Wait and See (W\&S) approach could be proposed.
experimental chemoradiotherapy
Procedure/SurgeryParticipants with cT2N0 rectal tumors are typically candidates for upfront surgical resection. The investigators propose an alternative approach based on experimental chemoradiotherapy (spCRT). Literature suggests that pathologic complete response (pCR) rates after CRT are significantly higher than the 25% described for intermediate-advanced tumors. The investigators will assess clinical complete response (cCR) or complete metabolic response (cMR) through a multidisciplinary restaging process, including MRI, PET, thorax-abdomen CT scan, ERUS, and rectoscopy. In participants achieving cCR or cMR, a Watch and Wait (W\&S) strategy or Local Excision/Transanal Minimally Invasive Surgery (LE/TAMIS) may be proposed to avoid the physical and psychological consequences of major surgery, followed by a rigorous surveillance program.
Standard Chemotherapy
Procedure/SurgeryTumors will be initially treated with standard CRT (stCRT). Patients who reach cCR-cMR at restaging they are already candidates to sparing approaches with W\&S/LE/TAMIS according to Multicentric Resarch Study Protocol
Development and Validation of a Clinical-Radiologic-Molecular Scoring System for Predicting Pathologic Complete Response (pCR) in Rectal Cancer
Quantification of the probability of achieving pathologic complete response (pCR) following chemoradiotherapy (CRT) through a composite scoring system integrating: Radiomic data from Pelvic MRI and PET Endoscopic findings (e.g., mucosal healing, residual lesion) Molecular markers (e.g., Microsatellite Instability \[MSI\], mutations in BER, SSB, and NER DNA repair pathways). Scoring Output: Probability value (0-1) or risk class (low, intermediate, high) for likelihood of pCR. Purpose: Stratify patients into low- or high-probability groups to support treatment decision-making (e.g., immediate surgery vs. organ-sparing strategies).
Success Rate of the Organ Sparing Approach (OSA)
Percentage of patients undergoing OSA who achieve a positive clinical response (defined as clinical complete response or stable disease without need for radical resection). Assessment Method: Clinical examination, imaging (MRI, PET), histological evaluation, and follow-up data. Unit of Measure: Percentage (%) of responders
Long-Term Disease-Free Survival in Patients Undergoing Organ Sparing Approach (OSA) vs. Radical Surgical Resection (RSR)
Comparison of local and distant recurrence rates between OSA and RSR groups. Assessment Tools: Proctoscopy Pelvic MRI CT scan of thorax and abdomen Whole-body PET Unit of Measure: Percentage (%) of patients without recurrence Definition of Outcome: Disease-free survival at 3 and 5 years post-treatment.
Short-Term General Cancer-Related Quality of Life (QoL) in OSA vs. Resection Groups
Evaluation of patient-reported general cancer-related quality of life using the EORTC QLQ-C30 questionnaire. Scores range from 0 to 100, with higher scores indicating better functioning. Measure: Units on EORTC QLQ-C30 scale (0-100)
Short-Term Colorectal Cancer-Specific Functioning in OSA vs. Resection Groups
Evaluation of patient-reported colorectal cancer-specific functioning using the EORTC QLQ-CR38 questionnaire. Scores range from 0 to 100, with higher scores indicating better quality of life. Measure: Units on EORTC QLQ-CR38 scale (0-100)
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