Local Regrowth and the Risk of Distant Metastases Among Patients Undergoing Watch-and-Wait for Rectal Cancer: What Is the Best Control Group? Multicenter Retrospective Study.

BACKGROUND: A proportion of rectal cancer patients who achieve a clinical complete response may develop local regrowth. Although salvage appears to provide appropriate local control, the risk of distant metastases is less known. OBJECTIVE: To compare the risk of distant metastases between patients who achieve a clinical complete response (watch-and-wait strategy) and subsequent local regrowth and patients managed by surgery after chemoradiation. DESIGN: Retrospective multicenter cohort study. SETTINGS: This study used data of patients from 3 institutions who were treated between 1993 and 2019. PATIENTS: Patients with initial clinical complete response (after neoadjuvant therapy) followed by local regrowth and patients with near-complete pathological response (≤10%) after straightforward surgery after chemoradiation were included. MAIN OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify risk factors for distant metastases. Kaplan-Meier curves were created (log-rank test) to compare survival outcomes. Analyses were performed using time zero as last day of radiation therapy or as date of salvage resection in the local regrowth group. RESULTS: Twenty-one of 79 patients with local regrowth developed distant metastases, whereas only 10 of 74 after upfront total mesorectal excision following neoadjuvant chemoradiation therapy ( p = 0.04). Local regrowth and final pathology (ypT3-4) were the only independent risk factors associated with distant metastases. When using date of salvage resection as time zero, distant metastases-free survival rates were significantly inferior for patients with local regrowth (70% vs 86%; p = 0.01). LIMITATIONS: Small number of patients, many neoadjuvant therapies, and selection bias. CONCLUSIONS: Patients undergoing watch-and-wait strategy who develop local regrowth are at higher risk for development of distant metastases compared to patients with near-complete pathological response managed by upfront surgery after chemoradiation. See Video Abstract. NUEVO CRECIMIENTO LOCAL Y EL RIESGO DE METSTASIS A DISTANCIA ENTRE PACIENTES SOMETIDOS A OBSERVACIN Y ESPERA POR CNCER DE RECTO CUL ES EL MEJOR GRUPO DE CONTROL ESTUDIO RETROSPECTIVO MUTICNTRICO: ANTECEDENTES:Una proporción de pacientes que logran una respuesta clínica completa pueden desarrollar un nuevo crecimiento local. Si bien el rescate parece proporcionar un control local apropiado, el riesgo de metástasis a distancia es menos conocido.OBJETIVO:Comparar el riesgo de metástasis a distancia entre los pacientes que logran una respuesta clínica completa (estrategia de observación y espera) y el nuevo crecimiento local posterior con los pacientes tratados con cirugía después de la quimiorradiación.DISEÑO:Estudio de cohorte multicéntrico retrospectivo.CONFIGURACIÓN:Este estudio utilizó datos de pacientes de 3 instituciones que fueron tratados entre 1993 y 2019.PACIENTES:Pacientes con respuesta clínica completa inicial (después de la terapia neoadyuvante) seguida de crecimiento local nuevo y pacientes con respuesta patológica casi completa (≤10 %) después de cirugía directa después de quimiorradiación.PRINCIPALES MEDIDAS DE RESULTADO:Se realizó un análisis univariante/multivariante para identificar los factores de riesgo de metástasis a distancia. Se crearon curvas de Kaplan-Meier (prueba de rango logarítmico) para comparar los resultados de supervivencia. El análisis se realizó utilizando el tiempo cero como último día de radioterapia (1) o como fecha de resección de rescate (2) en el grupo de recrecimiento local.RESULTADOS:Veintiuno de 79 pacientes con recrecimiento local desarrollaron metástasis a distancia, mientras que solo 10 de 74 después de una cirugía sencilla (p = 0,04). El recrecimiento local y la patología final (ypT3-4) fueron los únicos factores de riesgo independientes asociados con las metástasis a distancia. Cuando se utilizó la fecha de la resección de rescate como tiempo cero, las tasas de supervivencia sin metástasis a distancia fueron significativamente inferiores para los pacientes con recrecimiento local (70 frente a 86 %; p = 0,01).LIMITACIONES:Pequeño número de pacientes, muchas terapias neoadyuvantes, sesgo de selección.CONCLUSIONES:Los pacientes sometidos a observación y espera que desarrollan un nuevo crecimiento local tienen un mayor riesgo de desarrollar metástasis a distancia en comparación con los pacientes con una respuesta patológica casi completa manejados con cirugía por adelantado después de la quimiorradiación. (Traducción-Dr. Xavier Delgadillo ).

High-risk features in potentially resectable colon cancer: a prospective MDCT-pathology agreement study.

PURPOSE: Neoadjuvant chemotherapy in potentially resectable high-risk Stage II and Stage III colon cancer has demonstrated promising results in the PRODIGE 22-ECKINOXE Phase II trial. Identification of adverse morphologic features, namely T3 with >5 mm extramural extension/T4 stages and/or N2, is fundamental and requires accurate noninvasive imaging. Our aim was to assess the value of optimized preoperative MDCT to stratify potentially resectable colon cancer patients for neoadjuvant therapy. METHODS: this is an observational prospective cross-sectional radiologic-pathologic agreement study. All patients with colon cancer referred to our Institution's Radiology department for preoperative MDCT staging between 01-10-2013 and 11-02-2015 underwent independent reading based on axial and multiplanar reconstruction images by 3 radiologists with 3, 6, and 20 years of experience in gastrointestinal radiology. T stage, extramural extension if T3 (≤5 mm or >5 mm), and N stage were recorded. Surgical specimens subsequently obtained underwent micro-pathologic analysis by a gastrointestinal pathologist with 9 years of experience in gastrointestinal pathology. Main outcome measures were sensitivity, specificity, PPV, NPV, AUROC, diagnostic accuracy, and interobserver agreement of optimized MDCT, and pathologic analysis of the surgical specimen considered the reference standard. RESULTS: 74 patients [43 males; median age 73 (45-89)] were eligible. MDCT sensitivity, specificity, PPV, NPV, AUROC, and diagnostic accuracy ranged between 42.9-76.2, 75.5-90.6, 55.2-76.2, 80.0-90.6, 0.67-0.83 and 0.76-0.86%, respectively, for the identification of T3 > 5 mm/T4 disease, with moderate interobserver agreement (0.49); and 8.3-33.3, 93.5-98.4, 20-66.7, 84.1-88.2, 0.51-0.65 and 0.80-0.86%, respectively, for the identification of N2 disease, with absent interobserver agreement (0.10). CONCLUSIONS: Specificity of MDCT in the stratification of patients for neoadjuvant therapy may be high enough to prevent overtreatment. However, it may lead to undertreatment in a meaningful proportion of patients. Observer performance may benefit from targeted training programs, given the variability and observer dependence of the results. Limitations include 4-slice MDCT equipment, time to surgery and lack of long-term outcome information based on imaging parameters per se.

An ontogenetic approach to gynecologic malignancies.

UNLABELLED: Ontogenetic anatomy is the mapping of body compartments established during early embryologic development, particularly well demarcated in the adult pelvis. Traditional cancer surgery is based on wide tumour excision with a safe margin, whereas the ontogenetic theory of local tumour spread claims that local dissemination is facilitated in the ontogenetic compartment of origin, but suppressed at its borders in the early stages of cancer development. Optimal local control of cancer is achieved by whole compartment resection with intact margins following ontogenetic "planes". The principles embodied in this hypothesis are most convincingly supported by the results of the implementation of total mesorectal excision in rectal cancer, and more recently, by innovative surgical approaches to gynaecologic malignancies. The high resolution contrast of MR, accurately delineating pelvic fascial compartments, makes it the best imaging modality for gynaecologic cancer surgery planning following these principles, but requires interpretation of imaging anatomy from a different perspective. TEACHING POINTS: • Ontogenetic anatomy refers to mapping of embryologically determined body compartments. • Ontogenetic theory claims tumour growth is not isometrical, but rather compartment permissive. • Ontogenetic principles are highly supported by the outcome results of total mesorectal excision. • Innovative gynaecologic cancer surgery approaches based on ontogenetic theory show promising results.