Primary Tumor-Related Complications among Patients with Unresectable Stage IV Colorectal Cancer in the Era of Targeted Therapy: A Competing Risk Regression Analysis

BACKGROUND Whether prolonged survival with current chemotherapy using molecular target agents has changed the rate of primary tumor-related complications in patients with unresectable stage IV colorectal cancer is unclear. OBJECTIVE This study aimed to investigate the rate of primary tumor-related complications among patients receiving targeted therapy as compared with patients receiving chemotherapy without molecular target agents. DESIGN This was a retrospective review of data from a prospectively maintained database. SETTINGS The study was conducted at a high-volume multidisciplinary tertiary cancer center in Japan. PATIENTS Subjects were 352 consecutive patients with unresectable stage IV colorectal cancer who received systemic chemotherapy without primary tumor resection from 2001 to 2015. Patients were categorized into nontargeted and targeted groups according to the use of molecular target agents. MAIN OUTCOME MEASURES Complication rates attributed to primary tumors were measured. RESULTS Of the 352 patients, 159 were categorized into the nontargeted group and 193 patients into the targeted group. Competing risk-adjusted univariate analysis revealed that the primary tumor-related complication rates in the nontargeted group were 6.9% (95% CI, 3.8%-11.9%) at 1 year and 8.2% (95% CI, 4.8%-13.8%) at 2 years, whereas the targeted group had complication rates of 11.5% (95% CI, 7.5%-16.6%) at 1 year and 16.7% (95% CI, 12.4%-23.3%) at 2 years. Multivariate analysis revealed that the targeted group was ≈2 times more likely to have primary tumor-related complications (subdistribution HR = 2.04 (95% CI, 1.12-4.01); p = 0.020). Median survival time was 12.0 months in the nontargeted group and 24.1 months in the targeted group (p < 0.001). LIMITATIONS This study was limited by the retrospective design. CONCLUSIONS Targeted therapy was associated with a significantly increased risk of primary tumor-related complications during chemotherapy. However, targeted therapy also improved overall survival, making it a tolerable therapy. See Video Abstract at http://links.lww.com/DCR/B536. COMPLICACIONES PRIMARIAS RELACIONADAS CON EL TUMOR ENTRE PACIENTES CON CNCER COLORRECTAL EN ESTADIO IV IRRESECABLE EN LA ERA DE LA TERAPIA DIRIGIDA UN ANLISIS DE REGRESIN DEL RIESGO COMPETITIVO ANTECEDENTES:No esta claro si la supervivencia prolongada con la quimioterapia actual utilizando agentes moleculares dirigidos ha cambiado la tasa de complicaciones relacionadas con el tumor primario en pacientes con cancer colorrectal en estadio IV irresecable.OBJETIVO:Este estudio tuvo como objetivo investigar la tasa de complicaciones relacionadas con el tumor primario entre los pacientes que reciben terapia dirigida, en comparacion con pacientes que reciben quimioterapia sin agentes moleculares dirigidos.DISENO:Revision retrospectiva de datos de una base de datos mantenida prospectivamente.ESCENARIO CLINICO:Centro oncologico de tercer nivel multidisciplinario de alto volumen en Japon.PACIENTES:352 pacientes consecutivos con cancer colorrectal en estadio IV irresecable que recibieron quimioterapia sistemica sin reseccion del tumor primario entre 2001 y 2015. Los pacientes se clasificaron en grupos dirigidos y no dirigidos segun el uso de agentes moleculares dirigidos.PRINCIPALES MEDIDAS DE VALORACION:Tasas de complicaciones debidas a tumores primarios.RESULTADOS:De los 352 pacientes, 159 se clasificaron en el grupo no dirigido y 193 pacientes en el grupo dirigido. El analisis univariado ajustado al riesgo competitivo revelo que las tasas de complicaciones primarias relacionadas con el tumor en el grupo no dirigido fueron del 6,9% (intervalo de confianza (IC) del 95%, 3,8 - 11,9%) al ano y del 8,2% (IC del 95%, 4,8%). - 13,8%) a los dos anos, mientras que el grupo dirigido tuvo tasas de complicaciones del 11,5% (IC del 95%, 7,5 - 16,6%) al ano y del 16,7% (IC del 95%, 12,4 - 23,3%) a los dos anos. El analisis multivariado revelo que el grupo dirigido tenia aproximadamente dos veces mas probabilidades de tener complicaciones relacionadas con el tumor primario (razon de riesgo de subdistribucion, 2,04; IC del 95%, 1,12 a 4,01; p = 0,020). La mediana del tiempo de supervivencia fue de 12,0 meses en el grupo no dirigido y de 24,1 meses en el grupo dirigido (p <0,001).LIMITACIONES:Este estudio estuvo limitado por el diseno retrospectivo.CONCLUSIONES:La terapia dirigida se asocio con un riesgo significativamente mayor de complicaciones relacionadas con el tumor primario durante la quimioterapia. Sin embargo, la terapia dirigida tambien mejoro la SG, convirtiendola en una terapia tolerable. Consulte Video Resumen en http://links.lww.com/DCR/B536.