Background: While the incidence of cholangiocarcinoma is rising, little is known about young‐onset disease. We compared clinical characteristics and outcomes between patients with young‐onset cholangiocarcinoma, diagnosed between the ages of 18 and <50 years, and patients with typical‐onset cholangiocarcinoma, diagnosed at age 50 years or greater.Methods: We used the National Cancer Database to identify patients with young‐onset cholangiocarcinoma (n = 2520) and typical‐onset cholangiocarcinoma (n = 23,826). We compared the frequency of demographic and clinical characteristics between the two groups. We compared overall survival between the two groups using multivariable Cox regression analysis after adjusting for age, gender, race/ethnicity, comorbidity, facility type, tumor location, tumor stage, surgical status, and receipt of radiotherapy, chemotherapy and surgery.Results: When compared to patients with typical‐onset disease (median age 68 years), patients with young‐onset cholangiocarcinoma (median age 44 years) were more likely to be non‐White (35.0% vs. 27.4%, p < 0.01), and had lower overall comorbidity burden. Patients with young‐onset disease had a greater proportion of intrahepatic cholangiocarcinoma (56.0% vs. 45.5%, p < 0.001) and stage IV disease (50.5% vs. 43.5%, p < 0.001). Younger patients were more likely than typical‐onset patients to receive definitive surgery (30.9% vs. 25.0%, p < 0.001), radiation (27.7% vs. 19.6%, p < 0.001) and chemotherapy (73.1% vs. 50.1%, p < 0.001). In adjusted analyses, patients with young‐onset disease had a 15% decreased risk of death, compared with patients with typical‐onset disease (HR 0.85 [95% CI 0.80–0.89], p < 0.001).Conclusions: Patients with young‐onset cholangiocarcinoma may represent a demographically and clinically distinct group from those with more typical‐onset disease.

BACKGROUND: The watch-and-wait strategy provides an opportunity to pursue nonoperative management in rectal cancer patients with clinical complete response after neoadjuvant therapy. The management of those with near-complete response remains controversial. OBJECTIVE: We assessed the oncologic outcomes of patients managed by watch-and-wait versus total mesorectal excision according to clinical response to neoadjuvant therapy. DESIGN: Retrospective cohort study. SETTINGS: Comprehensive cancer center in New York. PATIENTS: Patients with rectal adenocarcinoma diagnosed between January 2006 and December 2020. INTERVENTIONS: A watch-and-wait strategy of active surveillance was offered to patients if they achieved clinical complete response. Salvage surgery was used for watch-and-wait patients with local regrowth. Patients with an incomplete response underwent total mesorectal excision. MAIN OUTCOME MEASURES: Local regrowth rate, organ preservation rate, disease-free survival, and overall survival. RESULTS: Patients with rectal adenocarcinoma (n = 1230) were divided into 3 response cohorts—incomplete (n = 646), near-complete (n = 189), and complete (n = 395). Eighty-one patients (43%) in the near-complete group and 351 patients (89%) in the complete group entered watch-and-wait. Three-year local regrowth rates were 40% and 24% in the near-complete and complete response cohorts, respectively. The 5-year organ preservation rate was 53% in near-complete responders and 73% in complete responders. Five-year disease-free survival increased with greater clinical response to neoadjuvant therapy, with intermediate outcomes noted for patients with a near-complete (73%) compared to complete (82%) or incomplete (68%) response. Overall survival at 5 years was similar between the 3 cohorts (complete 90%, near-complete 86%, and incomplete 85%). LIMITATIONS: Retrospective nature. CONCLUSIONS: Greater clinical response to neoadjuvant therapy is associated with improved oncologic outcomes. Near-complete responders may avoid surgery and still achieve high organ preservation rates yet experience greater local regrowth rates than clinical complete response patients. Ongoing prospective trials integrating watch-and-wait after complete response as determined by uniform criteria will bolster the work to help treating physicians better select patients who qualify for active surveillance. See Video Abstract. CORRELACIÓN ENTRE EL GRADO DE RESPUESTA CLÍNICA A LA TERAPIA NEOADYUVANTE CONTRA EL CÁNCER DEL RECTO Y LOS RESULTADOS ONCOLÓGICOS EN LA ERA DE OBSERVAR Y ESPERAR: ANTECEDENTES: La estrategia de observar y esperar brinda la oportunidad de buscar un tratamiento no quirúrgico en pacientes con cáncer del recto con respuesta clínica completa después de la terapia neoadyuvante. El tratamiento de aquellos con respuesta casi completa sigue siendo controversial. OBJETIVO: Evaluamos los resultados oncológicos de los pacientes tratados con observar y esperar versus escisión mesorrectal total según la respuesta clínica a la terapia neoadyuvante. DISEÑO: Estudio de cohorte retrospectivo. CONFIGURACIÓN: Centro oncológico integral en Nueva York. PACIENTES: Pacientes con adenocarcinoma rectal diagnosticado entre enero de 2006 y diciembre de 2020. INTERVENCIONES: Se ofreció una estrategia de observar y esperar de vigilancia activa a los pacientes si lograban una respuesta clínica completa. Se utilizó cirugía de rescate para pacientes en observar y esperar con recrecimiento local. Los pacientes con una respuesta incompleta se sometieron a escisión mesorrectal total. PRINCIPALES MEDIDAS DE RESULTADO: Tasa de recrecimiento local, tasa de preservación de órganos, supervivencia libre de enfermedad y supervivencia general. RESULTADOS: Los pacientes con adenocarcinoma rectal (n = 1230) se dividieron en 3 cohortes de respuesta: incompleta (n = 646), casi completa (n = 189) y completa (n = 395). Ochenta y un (43%) pacientes en el grupo casi completo y 351 (89%) pacientes en el grupo completo ingresaron en observar y esperar. Las tasas de recrecimiento local a tres años fueron del 40% y 24% en las cohortes de respuesta casi completa y completa, respectivamente. La tasa de preservación de órganos a 5 años fue del 53% en los respondedores casi completos y del 73% en los respondedores completos. La supervivencia libre de enfermedad a cinco años aumentó con una mayor respuesta clínica a la terapia neoadyuvante con resultados intermedios observados para pacientes con una respuesta casi completa (73%) en comparación con la completa (82%) o incompleta (68%). La supervivencia global a los 5 años fue similar entre las tres cohortes (completa 90%, casi completa 86% e incompleta 85%). LIMITACIONES: Naturaleza retrospectiva. CONCLUSIÓN: Una mayor respuesta clínica a la terapia neoadyuvante se asocia con mejores resultados oncológicos. Los pacientes con respuesta casi completa pueden evitar la cirugía y aun así lograr altas tasas de preservación de órganos, pero experimentar mayores tasas de recrecimiento local que los pacientes con respuesta clínica completa. Los ensayos prospectivos en curso que integran observar y esperar después de la respuesta completa según lo determinado por criterios uniformes reforzarán el trabajo para ayudar a los médicos tratantes a seleccionar mejor a los pacientes que califican para la vigilancia activa. (Traducción—Dr. Aurian Garcia Gonzalez)

Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan–Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11–47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5–66.5%), 54.5% (95% CI 44.4–66.8%), and 26.8% (95% CI 18.6–38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16–46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99–42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05–6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.

(1) Background: Adenosquamous carcinoma (ASC) is a rare subtype of colon cancer. Its rarity makes characterization challenging, although colonic ASC is believed to present at more advanced stages and have worse outcomes versus adenocarcinoma. This study aims to characterize the clinicopathological characteristics and clinical outcomes of colonic ASC. (2) Methods: This is a single-center, retrospective review of patients diagnosed with colonic ASC from 2000 to 2020. Data extracted included patient demographics, staging at diagnosis, tumor clinicopathologic and genetic characteristics, and clinical outcomes. (3) Results: Among 61,126 patients with colorectal cancer, 13 (0.02%) had colonic ASC, with a mean age at diagnosis of 48.7 years. The cecum/ascending colon was the most common primary site (6/13, 46.2%), and all except one patient was diagnosed with Stage III or IV disease. Among the eight patients with mismatch repair genetics available, only one was mismatch repair deficient. Eleven patients (84.6%) underwent surgery, and 11 likewise received some form of chemotherapy. Recurrence occurred in 7 of 13 patients (53.8%), and the overall five-year survival rate was 38.5%. The median survival rate was 39.4 months overall (30.5 months for Stage III, 23.7 months for Stage IV). (4) Conclusions: Overall, colonic ASC is rare, and this cohort of colonic ASC patients demonstrated advanced stage at diagnosis, frequent recurrence, and poor overall survival. Additional research remains to compare these characteristics with those of comparably staged adenocarcinoma and to develop specific management recommendations.