Type of recurrence is associated with disease-free survival after salvage surgery for locally recurrent rectal cancer.

PURPOSE: To compare the characteristics and outcomes of rectal cancer patients with local recurrence at a perianastomotic site (PA), a surgical field (SF) site, or in lateral lymph nodes (LLN). METHODS: A total of 114 consecutive patients who underwent surgery for recurrent, non-metastatic rectal cancer at a single comprehensive cancer center between 1997 and 2012 were grouped on the basis of radiographic assessment of type of recurrence: PA, 76 (67%) patients; SF, 25 (22%) patients; LLN, 13 (11%) patients. Demographic, clinical, and pathological features were compared between the three groups, as were disease-free survival (DFS) and overall survival (OS). RESULTS: Recurrence type was associated with positive circumferential margin in the primary resection (PA, 4 [6%]; SF, 4 [19%]; LLN, 3 [25%]; P = 0.027), prior neoadjuvant therapy for the primary tumor (PA, 57 [75%]; SF, 18 [72%]; LLN, 4 [31%]; P = 0.007), and location of the primary tumor in the upper rectum (PA, 33 [45%]; SF, 5 [23%]; LLN, 1 [8%]; P < 0.001). Patients with PA had longer median DFS (PA, 5.1 years; SF, 1.5 years; LLN, 1.2 years; P = 0.036). There was a non-significant trend toward longer OS and higher rates of R0 resection for PA. CONCLUSION: Type of recurrence after salvage surgery for locally recurrent rectal cancer is associated with longer DFS in patients with PA recurrence.

Patient-Reported Bowel Function in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy After Neoadjuvant Therapy: A Case-Control Study.

BACKGROUND: A watch-and-wait strategy is a nonoperative alternative to sphincter-preserving surgery for patients with locally advanced rectal cancer who achieve a clinical complete response after neoadjuvant therapy. There are limited data about bowel function for patients undergoing this organ-preservation approach. OBJECTIVE: The purpose of this study was to compare bowel function in patients with rectal cancer managed with a watch-and-wait approach with bowel function in patients who underwent sphincter-preserving surgery (total mesorectal excision). DESIGN: This was a retrospective case-control study using patient-reported outcomes. SETTINGS: The study was conducted at a comprehensive cancer center. PATIENTS: Twenty-one patients underwent a watch-and-wait approach and were matched 1:1 with 21 patients from a pool of 190 patients who underwent sphincter-preserving surgery, based on age, sex, and tumor distance from the anal verge. MAIN OUTCOME MEASURES: Bowel function was measured using the Memorial Sloan Kettering Cancer Center Bowel Function Instrument. RESULTS: Patients in the watch-and-wait arm had better bowel function on the overall scale (median total score, 76 vs 55; p < 0.001) and on all of the subscales, with the greatest difference on the urgency/soilage subscale (median score, 20 vs 12; p < 0.001). LIMITATIONS: The study was limited by its retrospective design, small sample size, and temporal variability between surgery and time of questionnaire completion. CONCLUSIONS: A watch-and-wait strategy correlated with overall better bowel function when compared with sphincter-preserving surgery using a comprehensive validated bowel dysfunction tool. See Video Abstract at http://links.lww.com/DCR/B218. FUNCIÓN EVACUATORIA INFORMADA POR PACIENTES EN CÁNCER RECTAL MANEJADO CON UNA ESTRATEGIA DE OBSERVAR Y ESPERAR DESPUÉS DE LA TERAPIA NEOADYUVANTE: UN ESTUDIO DE CASOS Y CONTROLES: Observar y esperar es una alternativa no operativa a la cirugía de preservación del esfínter para pacientes con cáncer rectal localmente avanzado que logran una respuesta clínica completa después de la terapia neoadyuvante. Hay datos limitados sobre la función evacuatoria en pacientes sometidos a este abordaje para preservación de órganos.Evaluar la función evacuatoria en pacientes con cáncer rectal manejados con observar y esperar comparado a pacientes sometidos a cirugía de preservación de esfínteres (escisión mesorrectal total).Estudio retrospectivo de casos y controles utilizando resultados reportados por pacientes.Centro especializado oncológico.21 pacientes se sometieron a observar y esperar y se compararon con 21 pacientes de un grupo de 190 pacientes que se sometieron a cirugía de preservación de esfínteres controlando por edad, sexo y la distancia del tumor al borde anal.Función evacuatoria utilizando un instrumento de valoración del Centro de Cáncer Memorial Sloan Kettering.Los pacientes de observar y esperar demostraron mejor función evacuatoria en la escala general (puntuación total media, 76 versus 55; p <0,001) y en todas las subescalas, con la mayor diferencia en la subescala de urgencia / ensuciamiento fecal (puntuación media, 20 versus 12; p <0,001).Diseño retrospectivo, numero de muestra pequeño y variabilidad temporal entre la cirugía y el tiempo de finalización del cuestionario.Observar y esperar se correlacionó con mejor función evacuatoria en general en comparación con la cirugía de preservación del esfínter utilizando una herramienta integral validada para la disfunción evacuatoria. Consulte Video Resumen en http://links.lww.com/DCR/B218. (Traducción-Dr. Adrián Ortega).

SMAD4 Loss in Colorectal Cancer Patients Correlates with Recurrence, Loss of Immune Infiltrate, and Chemoresistance.

PURPOSE: SMAD4 has shown promise in identifying patients with colorectal cancer at high risk of recurrence or death.Experimental Design: A discovery cohort and independent validation cohort were classified by SMAD4 status. SMAD4 status and immune infiltrate measurements were tested for association with recurrence-free survival (RFS). Patient-derived xenografts from SMAD4-deficient and SMAD4-retained tumors were used to examine chemoresistance. RESULTS: The discovery cohort consisted of 364 patients with stage I-IV colorectal cancer. Median age at diagnosis was 53 years. The cohort consisted of 61% left-sided tumors and 62% stage II/III patients. Median follow-up was 5.4 years (interquartile range, 2.3-8.2). SMAD4 loss, noted in 13% of tumors, was associated with higher tumor and nodal stage, adjuvant therapy use, fewer tumor-infiltrating lymphocytes (TIL), and lower peritumoral lymphocyte aggregate (PLA) scores (all P < 0.04). SMAD4 loss was associated with worse RFS (P = 0.02). When stratified by SMAD4 and immune infiltrate status, patients with SMAD4 loss and low TIL or PLA had worse RFS (P = 0.002 and P = 0.006, respectively). Among patients receiving 5-fluorouracil (5-FU)-based systemic chemotherapy, those with SMAD4 loss had a median RFS of 3.8 years compared with 13 years for patients with SMAD4 retained. In xenografted mice, the SMAD4-lost tumors displayed resistance to 5-FU. An independent cohort replicated our findings, in particular, the association of SMAD4 loss with decreased immune infiltrate, as well as worse disease-specific survival. CONCLUSIONS: Our data show SMAD4 loss correlates with worse clinical outcome, resistance to chemotherapy, and decreased immune infiltrate, supporting its use as a prognostic marker in patients with colorectal cancer.