Predictive Value of DNA Mismatch Repair System in Colorectal Cancers

NCT ID: NCT05871567

Last Updated: 2023-05-24

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 403 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-01-01
• Study Completion Date: 2023-03-31

Brief Summary

• Microsatellite instable (MSI) tumors represent almost the 15% of all sporadic colorectal cancers (CRCs).
• Literature data show that this unique tumor population appears to be poorly responsive to conventional chemotherapy and conversely reveals excellent results to immunotherapy.
• Our data, as demonstrated by propensity score-matched and win ratio analysis, show that there are no substantial differences between MSI and MSS tumors in early CRC stages treated with surgery alone.
• On the contrary, stable tumors (MSS) did much better than MSI tumors in advanced CRC stages undergoing conventional adjuvant treatment.
• Determination of status of DNA mismatch repair system is crucial in high-risk CRCs to optimize treatment.

Detailed Description

Colorectal cancers (CRCs) with deficient DNA mismatch repair (MMR) system (so called dMMR or MSI tumors) represent a no-negligible part of sporadic CRCs. Prognostic value of this unique cell population remains controversial, but undoubtedly these tumors are characterized by poor response to conventional chemotherapy, an high tumor mutational burden resulting in a brisk immuno response, and, as recently observed, excellent results to the immunotherapy. The aim of this study was to evaluate, by using sophisticated statistical analyses, the predictive value of MSI status and its optimal treatment.

A series of 403 consecutive CRC patients treated by the same oncological team from 2014 to 2021 entered the study. No patients underwent immunotherapy. Immunohistochemistry, integrated by polymerase chain reaction if appropriate, was used to categorize specimens in microsatellite stable (MSS) and instable (MSI) tumors. The win ratio (WR) approach was utilized to compare composite outcomes of MSS and MSI tumors while controlling for radical versus no radical resection, propensity score-matched analysis, and reversing primary endpoint.

Conditions

MSI-H Colorectal Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

group 1 or MSS

colorectal cancers (CRCs) with stable microsatellite

colorectal resection

Intervention Type: PROCEDURE

potential resective surgery

group 2 or MSI

colorectal cancers (CRCs) with unstable microsatellite

colorectal resection

Intervention Type: PROCEDURE

potential resective surgery

Interventions

colorectal resection

potential resective surgery

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• all consecutive CRC patients observed from January 2014 to December 2021

Exclusion Criteria

• Patients with suspected or confirmed Lynch's syndrome (12 patients) and rectal cancers (98 patients) undergoing neoadjuvant treatment

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 86 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Campania Luigi Vanvitelli

OTHER

Sponsor Role: lead

Responsible Party

Gennaro Galizia

Full Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gennaro Galizia, MD

Role: STUDY_DIRECTOR

University of Campania 'Luigi Vanvitelli'

Other Identifiers

Università Vanvitelli Napoli

Identifier Type: -

Identifier Source: org_study_id