Clinical trial NCT06823297: Can Neoadjuvant Chemoradiotherapy be Ommited in Mid-rectal Cancer: A Prospective, Observational Cohort
Official title: Can Neoadjuvant Chemoradiotherapy be Omitted in cT2N+ and cT3 Mid-rectal Cancer: A Prospective, Observational Cohort Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Mid-Rectal Cancer
Rectal Cancer Stage II
Rectal Cancer Stage III
Keywords: Mid-Rectal Cancer
Radiotherapy
Mesorectal fascia
Lead sponsor: Turkish Society of Colon and Rectal Surgery
Sponsor class: OTHER
Collaborators: name: Baskent University
name: Dokuz Eylul University
name: Halic University
name: Acibadem Kent Hospital
name: Istanbul Health and Technology University
First posted: 2025-02-12
Enrollment: 436
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Histologically proven rectal cancer patients with locally advanced disease (cT2N0-T3N0-N+), but without distant metastases or high-risk features such as mesorectal fascia involvement or adjacent organ invasion (cT4).

Brief summary: This project aims to compare the oncological and functional outcomes of patients with mid-rectal cancer who have a low risk of local recurrence (without MRF involvement) and who either receive or do not receive neoadjuvant chemoradiotherapy (nCRT).

Main Question:

H0: In mid-rectal cancer patients without MRF involvement (cT2N+ and cT3Nx), there is no difference in 3-year disease-free survival between direct TME and TME after nCRT.

H1: In mid-rectal cancer patients without MRF involvement (cT2N+ and cT3Nx), direct TME is associated with worse 3-year disease-free survival compared to TME after nCRT.

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.

Detailed description: 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 involvement of the circumferential resection margin (CRM) 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 observe whether upfront TME achieves similar 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

Primary outcomes:
measure: Disease-free survival (DFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 3 and 5 years
measure: Local Recurrence Rate
timeFrame: 3 years and 5 years
measure: Colorectal Cancer Specific Quality of Life
timeFrame: 1 year, 3 years and 5 years
measure: Bowel Dysfunction Related Quality of Life
timeFrame: 1 year, 3 years and 5 years
Other outcomes:
Locations:
city: Ankara
country: Turkey
facility: Baskent University
city: Istanbul
country: Turkey
facility: Istanbul Health and Technology University
city: Istanbul
country: Turkey
facility: Memorial sisli Hospital
city: Izmir
country: Turkey
facility: Acibadem Kent Hospital
city: Izmir
country: Turkey
facility: Dokuz Eylul University
Study officials:
affiliation: Baskent University
name: Feza Karakayali, Prof.
role: STUDY_CHAIR
affiliation: Acibadem Kent Hospital
name: Aras Emre Canda, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Halic University
name: Ilknur Erenler Bayraktar, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sisli Hospital
name: Onur Bayraktar, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Istanbul Health and Technology University
name: Cigdem N Arslan, Prof.
role: STUDY_DIRECTOR
affiliation: Dokuz Eylul University
name: Tayfun Bisgin, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Patel UB, Taylor F, Blomqvist L, George C, Evans H, Tekkis P, Quirke P, Sebag-Montefiore D, Moran B, Heald R, Guthrie A, Bees N, Swift I, Pennert K, Brown G. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol. 2011 Oct 1;29(28):3753-60. doi: 10.1200/JCO.2011.34.9068. Epub 2011 Aug 29.
citation: Ruppert R, Kube R, Strassburg J, Lewin A, Baral J, Maurer CA, Sauer J, Junginger T, Hermanek P, Merkel S; other members of the OCUM Group. Avoidance of Overtreatment of Rectal Cancer by Selective Chemoradiotherapy: Results of the Optimized Surgery and MRI-Based Multimodal Therapy Trial. J Am Coll Surg. 2020 Oct;231(4):413-425.e2. doi: 10.1016/j.jamcollsurg.2020.06.023. Epub 2020 Jul 19.
citation: Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rodel C, Cervantes A, Arnold D; ESMO Guidelines Committee. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv22-iv40. doi: 10.1093/annonc/mdx224. No abstract available.