Can Neoadjuvant Chemoradiotherapy be Ommited in Mid-rectal Cancer

NCT ID: NCT06823297

Last Updated: 2025-06-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

436 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-08-01

Study Completion Date

2035-08-01

Brief Summary

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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

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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.

Conditions

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Mid-Rectal Cancer Rectal Cancer Stage II Rectal Cancer Stage III

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Upfront TME group

Patients who underwent surgery without receiving neoadjuvant chemoradiotherapy

Total mesorectal excision

Intervention Type OTHER

Direct surgery without receiving neoadjuvant chemoradiotherapy

Neoadjuvant chemoradiotherapy group

Patients who received neoadjuvant chemoradiotherapy before surgery

Neoadjuvant Chemotherapy followed by total mesorectal excision

Intervention Type OTHER

Neoadjuvant chemoradiotherapy treatment regimens (including conventional chemoradiotherapy/radiotherapy/chemotherapy regimens or total neoadjuvant chemoradiotherapy regimens) before surgery

Interventions

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Total mesorectal excision

Direct surgery without receiving neoadjuvant chemoradiotherapy

Intervention Type OTHER

Neoadjuvant Chemotherapy followed by total mesorectal excision

Neoadjuvant chemoradiotherapy treatment regimens (including conventional chemoradiotherapy/radiotherapy/chemotherapy regimens or total neoadjuvant chemoradiotherapy regimens) before surgery

Intervention Type OTHER

Eligibility Criteria

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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
* Clinical local staging performed by MRI
* cT2N+, cT3N0 and cT3N+ tumors
* Patients without mesorectal fascia involvement assessed by MRI (≤1 mm)
* Patients without pathological (short axis ≥7 mm) lateral (extramesorectal) lymph nodes on MRI
* Patients without EMVI on MRI

Exclusion Criteria

* cT4 tumors
* Stage IV disease
* Patients with MSI (+) in TME pathology
* PAtients who received neoadjuvant immunotherapy
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Baskent University

OTHER

Sponsor Role collaborator

Dokuz Eylul University

OTHER

Sponsor Role collaborator

Halic University

OTHER

Sponsor Role collaborator

Acibadem Kent Hospital

OTHER

Sponsor Role collaborator

Istanbul Health and Technology University

OTHER

Sponsor Role collaborator

Turkish Society of Colon and Rectal Surgery

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Feza Karakayali, Prof.

Role: STUDY_CHAIR

Baskent University

Aras Emre Canda, Prof.

Role: PRINCIPAL_INVESTIGATOR

Acibadem Kent Hospital

Ilknur Erenler Bayraktar, Prof.

Role: PRINCIPAL_INVESTIGATOR

Halic University

Onur Bayraktar, Prof.

Role: PRINCIPAL_INVESTIGATOR

Memorial Sisli Hospital

Cigdem N Arslan, Prof.

Role: STUDY_DIRECTOR

Istanbul Health and Technology University

Tayfun Bisgin, Prof.

Role: PRINCIPAL_INVESTIGATOR

Dokuz Eylul University

Locations

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Baskent University

Ankara, , Turkey (Türkiye)

Site Status

Istanbul Health and Technology University

Istanbul, , Turkey (Türkiye)

Site Status

Memorial sisli Hospital

Istanbul, , Turkey (Türkiye)

Site Status

Acibadem Kent Hospital

Izmir, , Turkey (Türkiye)

Site Status

Dokuz Eylul University

Izmir, , Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

Central Contacts

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Cigdem N Arslan, Prof.

Role: CONTACT

+905421454435

Feza Karakayali, Prof.

Role: CONTACT

+905421454435

Facility Contacts

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Feza Karakayali, Prof.

Role: primary

Cigdem N Arslan, Prof.

Role: primary

Onur Bayraktar, Prof.

Role: primary

Aras Emre Canda, Prof

Role: primary

Tayfun Bisgin, Assoc. Prof.

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 21876084 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32697965 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28881920 (View on PubMed)

Other Identifiers

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KA24/461

Identifier Type: -

Identifier Source: org_study_id

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