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Surgical Outcomes in Metastatic Mismatch Repair-Deficient/Microsatellite Instability-High Colorectal Cancer After Disease Control With Immune Checkpoint Inhibitors: A Retrospective Observational Study.

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PMID40576174
JournalDiseases of the colon and rectum
Publication Date2025-06-27
Ingested2026-08-02 12:04 AM
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ABSTRACT

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BACKGROUND: Surgical intervention after systemic therapy improves prognosis in metastatic colorectal cancer. However, surgical outcomes after immune checkpoint inhibitor therapy remain controversial in patients with mismatch repair-deficient/microsatellite instability-high disease. OBJECTIVE: This study aimed to demonstrate the outcomes of patients with metastatic mismatch repair-deficient/microsatellite instability-high colorectal cancer who underwent curative surgery after achieving disease control with immune checkpoint inhibitors. DESIGN: This is a single-center retrospective observational study. SETTING: This study was conducted in a tertiary referral center in China. PATIENTS: The data of patients diagnosed with metastatic mismatch repair-deficient/microsatellite instability-high colorectal cancers between 2017 and 2023 were reviewed. Patients who achieved disease control after immune checkpoint inhibitors and underwent curative surgeries were enrolled. MAIN OUTCOME MEASURES: Pathological responses and survival outcomes were assessed. RESULTS: A total of 39 patients were enrolled. The median age was 41 years (range, 16-74). Pathological residuals were diagnosed in 38.5% of the patients (15/39), whereas 61.5% (24/39) achieved a pathological complete response. Mucinous adenocarcinoma (33.3% vs 4.2%; difference 29.1%; 95% CI, 3.9%-53.3%; p = 0.02) was associated with pathological residual, whereas extensive disease (residual lesions in 2 or more organs or 2 or more residual lesions in a single organ; 93.3% vs 62.5%; difference 30.8%; 95% CI, 7.7%-53.9%; p = 0.06) and liver/peritoneum residuals (93.3% vs 62.5%; difference 30.8%; 95% CI, 7.7%-53.9%; p = 0.06) suggested possible associations with pathological residual. Pathological complete response (HR 0.059; 95% CI, 0.007-0.500; p = 0.01), mucinous adenocarcinoma (HR 7.170; 95% CI, 1.438-35.759; p = 0.02), and a surgical interval of >1 year (HR 4.673; 95% CI, 1.003-21.779; p = 0.02) were observed to be associated with relapse-free survival. LIMITATIONS: Limitations include potential selection bias and a small sample size. CONCLUSIONS: Pathological residuals are relatively common and pose a threat for patients with metastatic mismatch repair-deficient/microsatellite instability-high colorectal cancers controlled via immune checkpoint inhibitors. Patients with mucinous adenocarcinoma, extensive disease, or liver/peritoneal involvement may benefit from surgical resection. See Video Abstract . RESULTADOS QUIRRGICOS EN CNCER COLORRECTAL METASTSICO CON DEFICIENCIA EN LA REPARACIN DE DESAJUSTES Y ALTA INESTABILIDAD DE MICROSATLITES TRAS EL CONTROL DE LA ENFERMEDAD CON INHIBICIN DE PUNTOS DE CONTROL INMUNITARIO UN ESTUDIO OBSERVACIONAL RETROSPECTIVO: ANTECEDENTES:La intervención quirúrgica tras el tratamiento sistémico mejora el pronóstico en el cáncer colorrectal metastásico. Sin embargo, los resultados quirúrgicos tras la inhibición de los puntos de control inmunitario siguen siendo controvertidos en pacientes con enfermedad con deficiencia en la reparación de desajustes/instabilidad microsatélite alta.OBJETIVO:El objetivo de este estudio fue demostrar los resultados de pacientes con cáncer colorrectal metastásico con deficiencia en la reparación de desajustes y alta inestabilidad de microsatélites que se sometieron a cirugía curativa tras lograr el control de la enfermedad con inhibición de los puntos de control inmunitario.DISEÑO:Se trata de un estudio observacional retrospectivo realizado en un único centro.ENTORNO:Este estudio se llevó a cabo en un centro terciario de referencia en China.PACIENTES:Se revisaron los datos de los pacientes diagnosticados con cáncer colorrectal metastásico con deficiencia en la reparación de desajustes y alta inestabilidad de microsatélites entre 2017 y 2023. Se incluyeron los pacientes que lograron el control de la enfermedad tras la inhibición de los puntos de control inmunitario y se sometieron a cirugías curativas.MEDIDAS DE RESULTADO PRINCIPALES:Se evaluaron las respuestas patológicas y los resultados de supervivencia.RESULTADOS:Se incluyó a un total de 39 pacientes. La mediana de edad fue de 41 años (rango, 16-74). Se diagnosticaron residuos patológicos en el 38,5 % (15/39) de los pacientes, mientras que el 61,5 % (24/39) logró una respuesta patológica completa. El adenocarcinoma mucinoso (33,3 % frente a 4,2 %, diferencia: 29,1 %, IC del 95 %: 3,9 %-53,3 %, p = 0,02) se asoció con residuos patológicos, mientras que la enfermedad extensa (lesiones residuales en ≥2 órganos o ≥2 lesiones residuales en un solo órgano) (93,3 % frente a 62,5 %, diferencia: 30,8 %, IC del 95 %: 7,7 %-53,9 %, p = 0,06) y residuos hepáticos/peritoneales (93,3 % frente a 62,5 %, diferencia: 30,8 %, IC del 95 %: 7,7 %-53,9 %, p = 0,06) sugirieron posibles asociaciones con residuos patológicos. Se observó una respuesta patológica completa (HR: 0,059, IC del 95 %: 0,007-0,500, p = 0,01), adenocarcinoma mucinoso (HR: 7,170, IC del 95 %: 1,438-35,759, p = 0,02) y un intervalo quirúrgico >1 año (HR: 4,673, IC del 95 %: 1,003-21,779, p = 0,02) se asociaron con la supervivencia sin recidiva.LIMITACIONES:Las limitaciones incluyen un posible sesgo de selección y un tamaño reducido de la muestra.CONCLUSIONES:Los residuos patológicos son relativamente comunes y suponen una amenaza para los pacientes con cáncer colorrectal metastásico con deficiencia en la reparación de mismatches/instabilidad microsatélite alta controlados mediante inhibidores de puntos de control inmunitario. Los pacientes con adenocarcinoma mucinoso, enfermedad extensa o afectación hepática/peritoneal pueden beneficiarse de la resección quirúrgica. (Traducción-Yesenia Rojas-Khalil ).

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PATIENT-FRIENDLY SUMMARY

Surgical Outcomes in Metastatic Mismatch Repair-Deficient/Microsatellite Instability-High Colorectal Cancer After Disease Control With Immune Checkpoint Inhibitors: A Retrospective Observational Study.

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