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: The incidence of rectal adenocarcinoma is rising in patients < 50 years old compared to those > 50. Nonoperative management and active surveillance have become a standard of care in rectal cancer treatment for those who achieve a complete response to neoadjuvant therapy; however, the use, safety and efficacy of this approach in different age groups has not been well described. OBJECTIVE: Examine oncological outcomes in patients with rectal adenocarcinoma managed by nonoperative management according to patient age. DESIGN: Retrospective cohort study SETTING: Comprehensive cancer center in New York. PATIENTS: Patients with rectal adenocarcinoma diagnosed between January 2006 and December 2020. MAIN OUTCOME MEASURES: Local regrowth, recurrence-free survival, distant metastasis-free survival, overall survival rates. RESULTS: A cohort of 430 patients with rectal adenocarcinoma who were treated with neoadjuvant therapy and entered watch-and-wait were included. Patients were divided into 3 groups according to age at diagnosis: early-onset (age < 50, n = 98), middle-aged (50-64, n = 163), and late-onset (65+, n = 169). No differences were noted in tumor distance from the anal verge ( p = 0.345) between groups. More patients in the early-onset cohort received induction chemotherapy with chemoradiation than late-onset patients, who more often received chemoradiation alone and had clinical stage I disease ( p = 0.015). Median follow-up time was 4.0years (IQR 2.6-5.5). The 3-year local regrowth rates in each group were 23.8% (95% CI: 15.2-32.4), 33.0% (95% CI: 25.6-40.4), and 26.1% (95% CI: 19.4-32.8) in the early, middle-aged, and late-onset patients, respectively ( p = 0.395). No associated differences in 5-year distant metastasis-free or recurrence-free survival rates were noted between the 3 age groups. The early-onset cohort had an associated superior disease-specific survival from the late-onset cohort. LIMITATIONS: Retrospective nature CONCLUSIONS: Early-onset rectal cancer patients have at least similar oncological outcomes compared to those in older age groups when treated non-operatively. These data provide reassurance when offering a watch-and-wait approach to patients with early-onset rectal cancer. See Video Abstract .