Can Neoadjuvant Chemoradiotherapy be Ommited in Mid-rectal Cancer: a Prospective, Observational, Non-inferiority Trial

The goal of this observational study is to learn about the oncologic outcome of omitting neoadjuvant chemoradiotherapy in cT2N+ and cT3Nx mid-rectal cancer without mesorectal fascia involvement.

The main question it aims to answer is:

Does upfront total mesorectal excision result in non-inferior 3-year disease-free survival when compared to neoadjuvant chemoradiotherapy and total mesorectal excision in cT2N+ and cT3Nx mid-rectal cancer without mesorectal fascia involvement?

Participants already taking both interventions as part of their regular medical care for rectal cancer will be recruited in a prospective database for 5 years.

Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment for patients with locally advanced rectal cancer. This approach has been shown to improve local control and reduce recurrence rates. However, there is no clear evidence showing the advantage of neoadjuvant CRT in high and middle rectal tumors without involvement of mesorectal fascia (MRF). The MERCURY study demonstrated that preoperative MRI-predicted positive CRM is an independent factor for local recurrence. Following this study, the selective use of nCRT in patients at high risk of local recurrence has been proposed.

The ESMO guidelines indicate that T3a/b rectal tumors located above the levator muscles, without circumferential resection margin (CRM) involvement or extramural venous invasion (EMVI), are associated with a very low risk of local recurrence. Consequently, they suggest that upfront TME may be an appropriate treatment option for this subgroup of patients. This recommendation remains unchanged in the presence of lymph node involvement within the same group. For clinically staged cT3a/b mid- or high-rectal tumors with clear CRM and no evidence of EMVI, the routine use of nCRT remains a subject of debate. If the surgeon consistently performs high-quality total mesorectal excision (TME), upfront surgery may be a suitable treatment option for this subgroup of patients.

In line with these recommendations, some surgeons perform upfront TME for patients with T2-3 node-positive mid-rectal cancer in the absence of MRF involvement. However, in these cases, the common approach is to administer neoadjuvant chemoradiotherapy. This study seeks to evaluate whether upfront TME achieves non-inferior 3-year disease-free survival compared to the standard approach of nCRT followed by TME in patients with cT2N+ and cT3Nx mid-rectal cancer without mesorectal fascia involvement.

Eligibility Criteria:
Inclusion Criteria:

* Pathologically confirmed rectal cancer
* Rectal cancer within 6-12 cm from anal verge confirmed by sigmoidoscopy or located between the anorectal junction and peritoneal reflection identified by MRI
* Clinically staged with MRI
* cT2N+, cT3N0 and cT3N+
* Patients without mesorectal fascia involvement assessed by MRI (≤1 mm)

Exclusion Criteria:

* cT4 tumors
* Stage IV disease
* Emergency surgery
* Clinical obstruction
* Previous pelvic radiotherapy
* Patients treated without a multidisciplinary council decision
* Inflammatory bowel diseases (Crohn's disease, Ulcerative colitis)
* Familial adenomatous polyposis (FAP), attenuated FAP, and other polyposis syndromes
* Hereditary non-polyposis colorectal cancer (Lynch syndrome)
* Synchronous colon tumors