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

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.

• Success Rate of the Organ Sparing Approach (OSA) [Time frame: 4 Years]
• Long-Term Disease-Free Survival in Patients Undergoing Organ Sparing Approach (OSA) vs. Radical Surgical Resection (RSR) [Time frame: 5 Years]
• Short-Term General Cancer-Related Quality of Life (QoL) in OSA vs. Resection Groups [Time frame: Baseline (before CRT), Post-CRT, Post-surgery, 6-month follow-up, 12-month follow-up]
• Short-Term Colorectal Cancer-Specific Functioning in OSA vs. Resection Groups [Time frame: Baseline (before CRT), Post-CRT, Post-surgery, 6-month follow-up, 12-month follow-up]
• Bowel Dysfunction After Rectal Surgery (Low Anterior Resection Syndrome - LARS) in OSA vs. Resection Groups [Time frame: Baseline (before CRT), Post-CRT, Post-surgery, 6-month follow-up, 12-month follow-up]