Clinical trial NCT05871567: Predictive Value of DNA Mismatch Repair System in Colorectal Cancers
Official title: Assessment of the DNA Mismatch Repair System is Crucial in Colorectal Cancers Necessitating Adjuvant Treatment: a Propensity Score-matched and Win Ratio Analysis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: MSI-H Colorectal Cancer
Keywords: Colorectal cancers;
DNA mismatch repair;
Win ratio
Lead sponsor: University of Campania Luigi Vanvitelli
Sponsor class: OTHER
First posted: 2023-05-23
Enrollment: 403
Sex: ALL
Minimum age (years): 18
Maximum age (years): 86
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: CRC patients undergoing surgery

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.

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

Primary outcomes:
measure: survival rate
timeFrame: "From date of surgical operation until the date of death from any cause assessed up to 60 months"
Secondary outcomes:
measure: recurrence rate
timeFrame: "From date of surgical operation until the date of documented tumor recurrence assessed up to 60 months"
Other outcomes:
Locations:
Study officials:
affiliation: University of Campania 'Luigi Vanvitelli'
name: Gennaro Galizia, MD
role: STUDY_DIRECTOR
References: