Perineural Invasion Is a Prognostic but not a Predictive Factor in Nonmetastatic Colon Cancer.

Published on Oct 1, 2019in Diseases of The Colon & Rectum3.991
· DOI :10.1097/DCR.0000000000001450
Lieve G. J. Leijssen6
Estimated H-index: 6
(Harvard University),
Anne M. Dinaux8
Estimated H-index: 8
(Harvard University)
+ 4 AuthorsDavid H. Berger75
Estimated H-index: 75
(Harvard University)
BACKGROUND: Perineural invasion is associated with adverse oncological outcomes in colorectal cancer. However, data regarding the prognostic and predictive impact in colon cancer are scarce. OBJECTIVE: This study aims to clarify the role of perineural invasion in patients with nonmetastatic colon cancer. DESIGN: This study is a retrospective review of a prospectively maintained database. SETTINGS: This study took place at a tertiary medical center. PATIENTS: Patients with stage I to III colon cancer who underwent elective surgery at our tertiary center between 2004 and 2015 (n = 1145) were included. MEAN OUTCOME MEASURES: The primary long-term outcomes include disease-free survival, disease-specific survival, and overall survival. Differences were determined by multivariate Cox regression models adjusted for stage and potential confounders. RESULTS: Perineural invasion was identified in 215 patients (18.8%) and associated with emergency procedures, male sex, and advanced disease. Histopathological features including lymphatic and extramural vascular invasion, poor differentiation, and infiltrating tumor borders were correlated with perineural invasion. Compared with patients with perineural invasion-negative tumors, patients who had perineural invasion-positive tumors had worse disease-free, overall, and disease-specific survival (all p < 0.001). Moreover, patients with perineural invasion-positive node-negative disease had worse overall survival than patients with perineural invasion-negative node-positive disease (p < 0.001). After adjustment, perineural invasion remained significantly associated with worse disease-free survival (HR, 1.45; 95% CI, 1.03-2.03; p = 0.033), worse overall survival (HR, 1.75; 95% CI, 1.33-2.31; p < 0.001), and worse disease-specific survival (HR, 1.52; 95% CI, 1.00-2.30; p = 0.048). However, we did not find a significant predictive response with adjuvant chemotherapy in perineural invasion-positive node-negative tumors (HR, 2.10; 95% CI, 0.80-5.51; p = 0.122). The predictive value was only demonstrated in stage III disease with a significant impaired overall survival in patients with perineural invasion-positive tumors who did not receive adjuvant therapy (HR, 0.23; 95% CI, 0.13-0.40; p < 0.001). LIMITATIONS: This study was limited by its retrospective design. CONCLUSION: Our study confirms the prognostic value of perineural invasion in stage I to II and III colon cancer. However, patients with node-negative disease and perineural invasion did not significantly benefit from adjuvant therapy. More information regarding postoperative treatment in node-negative perineural invasion-positive colon cancer is required. See Video Abstract at LA INVASION PERINEURAL COMO FACTOR PRONOSTICO NO PREDICTIVO EN EL CANCER DE COLON NO METASTASICO: La invasion perineural se encuentra asociada a resultados oncologicos adversos en casos de cancer colorrectal. Sin embargo, los datos sobre el impacto pronostico y predictivo en caso de cancer de colon son pocos. OBJETIVO: Definir el papel de la invasion perineural en pacientes con cancer de colon no metastasico. DISENO:: Revision retrospectiva de una base de datos alimentada prospectivamente. AJUSTES: Centro hospitalario de atencion terciaria. PACIENTES: Todos aquellos portadores de un cancer de colon estadio I-III que se sometieron a cirugia electiva en nuestro centro entre 2004-2015 (n = 1145). PRINCIPALES RESULTADOS: Los resultados a largo plazo incluyeron la supervivencia sin enfermedad, la supervivencia especifica de la enfermedad y la supervivencia general. Las diferencias se determinaron mediante modelos de regresion multivariantes de Cox, ajustados para el control de factores de confusion durante el analisis por estratificacion. RESULTADOS: La invasion perineural fue identificada en 215 pacientes (18.8%) y se la asocio con procedimientos de emergencia, al genero masculino y a la enfermedad avanzada. Las caracteristicas histopatologicas que incluyeron la invasion vascular linfatica y extramural, la diferenciacion deficiente y los bordes tumorales infiltrantes se correlacionaron con la invasion perineural. Comparativamente con los tumores sin invasion perineural, los pacientes positivos a la invasion perineural tuvieron una peor supervivencia general, libre y especifica de la enfermedad (todos p < 0.001). Asimismo, aquellos pacientes con invasion-perineural con ganglios negativos tuvieron una supervivencia global mucho peor que aquellos pacientes con ganglios positivos e invasion perineural negativa (p < 0.001). Despues del ajuste, la invasion perineural se asocio significativamente con una peor supervivencia sin la enfermedad (HR, 1.45; IC 95%, 1.03-2.03; p = 0.033), supervivencia general (HR, 1.75; IC 95%, 1.33-2.31; p <0.001), asi como con una peor supervivencia especifica de la enfermedad (HR, 1.52; IC 95%, 1.00-2.30; p = 0.048). Sin embargo, no encontramos una respuesta predictiva significativa con quimioterapia adyuvante en los tumores acompanados de invasion-perineural con ganglios negativos (HR, 2.10; IC del 95%, 0.80-5.51; p = 0.122). El valor predictivo solo fue demostrado en aquellos casos de estadio III con un deterioro significativo de la supervivencia global en pacientes con tumores perineurales positivos a la invasion y que no recibieron tratamiento adyuvante (HR, 0.23; IC 95%, 0.13-0.40; p < 0.001). LIMITACIONES: Diseno retrospectivo. CONCLUSION:: Nuestros resultados confirman el valor pronostico de la invasion perineural en el cancer de colon estadios I-II y III. Sin embargo, los pacientes con enfermedad ganglionar negativa e invasion perineural no se beneficiaron significativamente de la terapia adyuvante. Se requiere mas informacion sobre el tratamiento postoperatorio en el cancer de colon positivo para la invasion perineural con ganglios negativos. Vea el Resumen del video en
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