BACKGROUND:Watch-and-wait management (WW) of rectal cancer is accepted for select patients with a complete clinical response (cCR) to neoadjuvant therapy (NAT). The appropriateness of WW for cancers beyond the reach of digital rectal examination (DRE) and/or with a delayed cCR is unclear. METHODS:In this retrospective multicenter study, tumor palpability and clinical response were determined after NAT. Local regrowth-free survival (LRFS), disease-free survival (DFS), rectal organ preservation (OP), and salvage surgery outcomes were assessed. RESULTS:Among 477 patients, 427 (90%) had palpable tumers, with initial cCR in 389 (91%) and delayed cCR in 38 (9%) patients, respectively, whereas 50 (10%) had nonpalpable tumors, with initial pCR in 38 (76%) and delayed pCR in 12 (24%) patients, respectively (p < 0.01). The 3-year LRFS rate was 81.4% (95% confidence interval [CI], 76.6-86.2%) for palpable tumors and 74.3% (95% CI, 61.0-88.6%) for nonpalpable tumors. The DFS rates were 80.8 % (95 % CI, 75.9-85.7%) and 74.3% (95% CI, 61.0-88.6%), respectively. The 3-year rectal OP rate was 82.7% (95% CI, 77.9-87.5%) and 76.0% (95%, CI, 62.9-89.1%), respectively, with no difference in the survival curves for these three outcomes. (all p > 0.05). The patients with initial cCR or delayed cCR also had no differences in LRFS, DFS, or OP, but the interval to each of these outcomes were decreased with delayed cCR (all p < 0.01). CONCLUSION:Watch-and-wait management of rectal tumors beyond the reach of DRE is appropriate, with oncologic and rectal organ preservation rates that do not differ from patients with palpable tumors. In comparison to cancers with initial cCR, cancers with delayed cCR have accelerated intervals to local regrowth, disease recurrence, and rectal organ loss.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Liquid biopsy by peripheral blood circulating tumor DNA (ctDNA) measurement has emerged as a promising biomarker in the management of CRC. We aimed to summarize the current landscape of ctDNA assessment in CRC by briefly addressing relevant technicalities of ctDNA assays, reviewing the current body of evidence regarding the utility of ctDNA across the clinical spectrum, and providing considerations and prospectus for the future of ctDNA in CRC. Data from prospective trials investigating the use of ctDNA in CRC is rapidly accumulating. Positive ctDNA status is a strong prognostic factor for recurrence, now recognized in cancer treatment guidelines, and is emerging as a potential guide for adjuvant therapies in the setting of resected localized and metastatic disease. Mounting evidence also suggests that ctDNA measurement can potentially have a meaningful impact for CRC screening, multi-cancer early detection, and longitudinal surveillance of tumor biology in the setting of systemic therapies such as anti-EGFR rechallenge. There is a paucity of randomized controlled trial data supporting ctDNA use. ctDNA assessment may improve the clinician’s ability to gain granular information about tumor biology and activity across the spectrum of CRC. The results of ongoing randomized trials will further inform the value of routine ctDNA testing while helping steer future investigation

Contemporary cancer research prioritizes clinical endpoints such as overall survival (OS) and disease-free survival (DFS). However, definition of the starting point, “time zero,” for time-to-event analyses remains inconsistent in the rectal cancer nonoperative management (NOM) literature, affecting study comparisons. Moreover, the traditional definition of DFS for NOM is complicated given the success of salvage surgery for local regrowth (LR). Our aim was to evaluate how these definitions affect estimates of OS, LR, and DFS. We analyzed both a single-institution and a multi-institution cohort of patients with rectal cancer on NOM, shifting time zero from diagnosis to the post-treatment response assessment and to the date of clinical complete response (cCR) determination. In the single-institution NOM cohort of 85 patients, shifting time zero from diagnosis to cCR determination led to a median 5-year OS decrease of 5

BACKGROUND:The use of a watch-and-wait management strategy after a complete clinical response to neoadjuvant therapy for rectal cancer is increasing. However, insights into implementation, treatments, and outcomes on a national level in the United States are limited. OBJECTIVE:To investigate and report on watch-and-wait management practices and outcomes in the United States. DESIGN:Retrospective study. SETTING:Multicenter. PATIENTS:Patients with stage II or III rectal cancer who underwent intentional watch-and-wait management between January 2015 and August 2022. MAIN OUTCOME MEASURES:Patient and tumor characteristics, neoadjuvant treatment and response, local cancer regrowth and metastasis, salvage surgery, overall survival, and disease-specific survival. RESULTS:Among 545 patients from 33 centers, follow-up was 21 months (range, 9-37). Total neoadjuvant therapy or other types of neoadjuvant therapy were used in 395 (72%) and 150 (28%) patients, respectively. The estimated 3-year local regrowth rate was 23.8% (95% CI, 19.1%-29.4%). Patients with local regrowth had higher distant metastases incidence (14.2% vs 3.5%, p < 0.001). Salvage surgery was performed in 74 of 84 patients (88%) with local regrowth and included rectal resection in 66 patients (89%) and local excision in 8 (11%). Of 64 salvage resections with known pathology results, 58 (91%) were margin-negative. Overall, 3-year overall survival was 94.8% (95% CI, 90.5%-97.2%) and 3-year disease-specific survival was 96.2% (95% CI, 91.8%-98.2%). Patients with and without local regrowth exhibited 3-year overall survival of 83.6% (95% CI, 68.4%-91.9%) and 97.7% (95% CI, 93.3%-99.2%), respectively. LIMITATIONS:Retrospective study. CONCLUSIONS:This multicenter study indicates that the watch-and-wait approach for locally advanced rectal cancer is feasible with acceptable outcomes across a variety of geographical regions and practice settings in the United States. Local regrowth and distant metastasis rates were within published norms and salvage surgery proved effective. See Video Abstract . MANEJO DE ESPERA Y OBSERVACIN DEL CNCER RECTAL EXPERIENCIA DE PACIENTES DEL GRUPO DE INVESTIGACIN DEL CNCER RECTAL DE EE UU:ANTECEDENTES:El uso de una estrategia de manejo de observación y espera después de una respuesta clínica completa a la terapia neoadyuvante para el cáncer de recto está aumentando. Sin embargo, los conocimientos sobre la implementación, los tratamientos y los resultados, a nivel nacional de los Estados Unidos, son limitados.OBJETIVO:Investigar e informar sobre las prácticas y los resultados del manejo de observación y espera en los EE. UU.DISEÑO:Estudio retrospectivo.ESCENARIO:Multicéntrico.PACIENTES:Pacientes con cáncer de recto en estadio II o III que se sometieron a un manejo de observación y espera intencional entre enero de 2015 y agosto de 2022.PRINCIPALES MEDIDAS DE RESULTADOS:Características del paciente y del tumor, tratamiento neoadyuvante y respuesta, recrecimiento local del cáncer y metástasis, cirugía de rescate, supervivencia general y específica de la enfermedad.RESULTADOS:Entre 545 pacientes de 33 centros, el seguimiento fue de 21 meses (rango, 9-37). Se utilizó terapia neoadyuvante total u otros tipos de neoadyuvancia en 395 (72%) y 150 (28%) de los pacientes, respectivamente. La tasa estimada de recrecimiento local a 3 años fue del 23,8% (IC del 95%: 19,1-29,4%). Los pacientes con recrecimiento local tuvieron una mayor incidencia de metástasis a distancia (14,2% frente a 3,5%, p < 0,001). Se realizó cirugía de rescate en 74/84 (88%) pacientes con recrecimiento local e incluyó resección rectal en 66 (89%) y escisión local en 8 (11%). De 64 resecciones de rescate con resultados patológicos conocidos, 58 (91%) fueron márgenes negativos. En general, la supervivencia global a los 3 años fue del 94,8 % (IC del 95 %: 90,5-97,2 %) y la supervivencia específica de la enfermedad a los 3 años del 96,2 % (IC del 95 %: 91,8-98,2 %). Los pacientes con y sin recrecimiento local mostraron una supervivencia global a los 3 años del 83,6 % (IC del 95 %: 68,4-91,9 %) y del 97,7 % (IC del 95 %: 93,3-99,2 %), respectivamente.LIMITACIONES:Estudio retrospectivo.CONCLUSIÓN:Este estudio multicéntrico indica que el enfoque de observación y espera para el cáncer rectal localmente avanzado es factible con resultados aceptables en una variedad de regiones geográficas y entornos de práctica en los EE. UU. Las tasas de recrecimiento local y metástasis a distancia estuvieron dentro de las normas publicadas y la cirugía de rescate resultó eficaz. (Traducción-Dr Yolanda Colorado ).

Shogan, Benjamin D. M.D.; Vogel, Jon D. M.D.; Davis, Bradley R. M.D.; Keller, Deborah M.D.; Ayscue, Jennifer M M.D.; Goldstein, Lindsey E. M.D.; Feingold, Daniel L. M.D.; Lightner, Amy L. M.D.; Paquette, Ian M. M.D.; On behalf of the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons Author Information

Supplemental Table 1: Molecular and clinical characteristics of the 10 CRC explants used in the PDX model experiments. Seven explants have a KRAS mutation, 4 have a PIK3CA mutation, and none have a BRAF mutation. Over half of the explants came from patients who had previously received treatment for mCRC. Supplemental Table 2: Using DCE-MRI measurements, treatment with cabozantinib demonstrated significant decrease in vascularity on day 28 compared to baseline and day 7. Regorafenib treatment did not demonstrate a decrease in vascularity. Supplemental Table 3: [18F] FDG-PET imaging revealed significantly reduced FDG avidity on days 7 and days 28 of cabozantinib treatment compared to baseline, whereas FDG avidity did not diminish in the regorafenib treated explants. Supplemental Table 4: To better understand the potential metabolic effects of cabozantinib, we analysed signalling pathways involved in metabolism using the KEGG database. Receptor tyrosine kinase (RTK) assay revealed a decrease in many of the pathways responsible for cell metabolism after 3 days of cabozantinib treatment in three of the sensitive CRC explants. Supplemental Figure 1: Cabozantinib and regorafenib treatment in a Humanized HGF mouse model. Cabozantinib had greater antitumor effects when compared to regorafenib in the hHGF scid mice in CRC203 and CRC020. Similar results were observed when compared to athymic nude mice for CRC203 (REG TGII: 39.3, Cabo TGII: 14.93) and CRC020 (REG TGII: 17.5, Cabo TGII: -5.68). Supplemental Figure 2: Changes in TIE2 and VEGFR2 expression were variable and did not demonstrate a sustained decrease after treatment with regorafenib. Supplemental Figure 3: After 7 days of regorafenib treatment, there was no significant reduction in activation of p-AXL, AKT, and pS6 compared to control, and there was a variable trend in p-MET and p-RET levels as measured by RTK assay. Supplemental Figure 4: Regorafenib treatment led to decreased ATG3, LC3A/B, and beclin-1 in the CRC098 explant; however, levels of these enzymes increased in the CRC162 explant. Supplemental Figure 5: In vitro analysis of caspase 3/7 expression in cell lines HCT116 (a, c) and HT29 (b, d) after cabozantinib and crizotinib treatment showed significant increase in autophagy index relative to control*** and to regorafenib###. Caspase 3/7 expression was measured via fluorescence using the CYTO-ID® Autophagy Detection Kit. Crizotinib combined with SBI-020695, an anti-ULK-1 agent, did not result in increased caspase 3/7 expression, whereas caspase 3/7 expression significantly increased with cabozantinib plus SBI-020695.

BACKGROUND: Total neoadjuvant therapy in rectal cancer may increase pathological complete response rates, potentially allowing for a nonoperative approach. OBJECTIVE: The objective of this study was to identify patient and tumor characteristics that predict a complete response following total neoadjuvant therapy. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted at a university-based National Cancer Institute–designated Comprehensive Cancer Center. PATIENTS: The patients include those with stage 2 or 3 rectal adenocarcinoma. INTERVENTIONS: Interventions included total neoadjuvant therapy, total mesorectal excision, and nonoperative management. MAIN OUTCOME MEASURES: Complete response was defined as either patients with a clinical complete response undergoing nonoperative management who remained cancer-free or patients undergoing surgery with a pathological complete response. RESULTS: Among 102 patients, median age was 54 years, 69% were male, median carcinoembryonic antigen level was 3.0 ng/mL, and the median distance of the tumor above the anorectal ring was 3 cm. Thirty-eight (37%) patients had a complete response, including 15 of 18 (83%) nonoperative patients who remained cancer free at a median of 22 months (range, 7–48 months) and 23 of 84 (27%) patients who underwent surgery and had a pathological complete response. The incomplete response group consisted of 61 patients who underwent initial surgery and 3 nonoperative patients with regrowth. There were no differences in gender, T-stage, or tumor location between groups. Younger age (median, 49 vs 55 years), normal carcinoembryonic antigen (71% vs 41%), clinical node-negative (24% vs 9%), smaller tumors (median 3.9 vs 5.4 cm), and wild-type p53 (79% vs 47%) and SMAD4 (100% vs 81%) were more likely to have a complete response (all p < 0.05). LIMITATIONS: This was a retrospective study with a small sample size. CONCLUSIONS: In patients with rectal cancer treated with total neoadjuvant therapy, more than one-third will achieve a pathological complete response or sustained clinical complete response with nonoperative management, making oncological resection superfluous in these patients. Smaller, wild-type p53 and SMAD4, and clinically node-negative cancers are predictive features of a complete response. See Video Abstract at http://links.lww.com/DCR/B889. CÁNCER DE RECTO: PREDICTORES CLÍNICOS Y MOLECULARES DE UNA RESPUESTA COMPLETA A LA TERAPIA NEOADYUVANTE TOTAL ANTECEDENTES: La terapia neoadyuvante total en el cáncer de recto puede aumentar las tasas de respuesta patológica completa y permitir potencialmente un enfoque no quirúrgico. OBJETIVO: El objetivo fue identificar las características tanto del paciente y del tumor que logren predecir una respuesta completa después de la terapia neoadyuvante total. DISEÑO: Este fue un estudio de cohorte retrospectivo. AJUSTES: Este estudio se realizó en un Centro Integral de Cáncer designado por el Instituto Nacional del Cáncer con sede universitaria. PACIENTES: Los pacientes incluyen aquellos con adenocarcinoma de recto en estadio 2 o 3. INTERVENCIONES: Terapia neoadyuvante total, escisión total del mesorrecto, manejo conservador no quirúrgico. PRINCIPALES MEDIDAS DE RESULTADO: La respuesta completa se definió como pacientes con una respuesta clínica completa sometidos a tratamiento no quirúrgico que permanecieron libres de cáncer o pacientes sometidos a cirugía con una respuesta patológica completa. RESULTADOS: Entre 102 pacientes, la mediana de edad fue de 54 años, el 69% fueron hombres, la mediana del nivel de antígeno carcinoembrionario fue de 3.0 ng/ml y la mediana de la distancia del tumor por encima del anillo anorrectal fue de 3 cm. Thirty-eight (37%) pacientes tuvieron una respuesta completa que incluyó a 15 de 18 (83%) pacientes con manejo no operatorio y que permanecieron libres de cáncer en una mediana de 22 meses (rango 7- 48 meses) y 23 de 84 (27%) pacientes que fueron sometidos a cirugía y tuvieron una respuesta patológica completa. El grupo de respuesta incompleta consistió en 61 pacientes que fueron sometidos inicialmente a cirugía y 3 pacientes no quirúrgicos con recrecimiento. No se encontró diferencias de género, estadio T o ubicación del tumor entre los grupos. Edad más joven (mediana 49 frente a 55), antígeno carcinoembrionario normal (71% frente a 41%), ganglios clínicos negativos (24% frente a 9%), tumores más pequeños (mediana de 3,9 frente a 5,4 cm) y p53 de tipo salvaje (79 % vs 47%) y SMAD4 (100% vs 81%) tenían más probabilidades de tener una respuesta completa (todos p < 0,05). LIMITACIONES: Este fue un estudio retrospectivo y con un tamaño de muestra pequeño. CONCLUSIONES: En pacientes con cáncer de recto tratados con terapia neoadyuvante total, más de un tercio logrará una respuesta patológica completa o una respuesta clínica completa sostenida con manejo no operatorio, logrando que la resección oncológica sea superflua en estos pacientes. Los cánceres más pequeños, clínicamente con ganglios negativos, con p53 de tipo salvaje y SMAD4, son características predictoras de una respuesta completa. Consulte Video Resumen en http://links.lww.com/DCR/B889. (Traducción—Dr. Osvaldo Gauto)

Total neoadjuvant therapy for locally advanced rectal cancer may include induction chemotherapy and chemoradiation or short-course radiotherapy and consolidative chemotherapy. Patients with clinical stage 2 or 3 rectal cancer who received induction chemotherapy followed by long-course chemoradiation at the University of Colorado (2016–2020) or short-course radiotherapy followed by consolidative chemotherapy at Washington University (2017–2020) were assessed. Eighty-four patients received induction chemotherapy and chemoradiation and 83 received short-course radiotherapy and consolidative chemotherapy. Among patients with complete re-staging evaluation, clinical complete response rates were similar, 49% (18/37) and 53% (44/83), respectively (p = 0.659). In the induction chemotherapy and chemoradiation group, 80% (n = 67) underwent surgery and 28% (n = 19) achieved a pathologic complete response. In the short-course radiotherapy and consolidative chemotherapy group, 44 (53%) patients underwent surgery and 11% (n = 5) had a pathologic complete response. Overall, a complete response was observed in 43% (n = 36) of patients who received induction chemotherapy and chemoradiation compared to 53% (n = 44) who received short-course radiotherapy and consolidative chemotherapy (p = 0.189). Perioperative outcomes were similar in patients who received induction chemotherapy and chemoradiation compared to short-course radiotherapy and consolidative chemotherapy: intraoperative complications (2% vs 7%), complete mesorectal specimen (85% vs 84%), anastomotic leak (9% vs 7%), organ/space infection (9% vs 5%), readmission (19% vs 21%), and reoperation (8% vs 9%), respectively (all p > 0.05). In patients with clinical stage 2 or 3 rectal cancer, total neoadjuvant therapy with either induction chemotherapy and chemoradiation or short-course radiotherapy followed by consolidative chemotherapy were associated with similar perioperative morbidity and complete response rates.

BACKGROUND: In patients with ulcerative colitis who undergo IPAA, a diverting ileostomy is used to diminish the severity of anastomotic complications. Typically, the ileostomy is closed after an interval of 2 to 4 months. The safety of earlier closure of the ileostomy after pouch surgery is unknown. OBJECTIVE: This study aimed to compare postoperative outcomes in patients randomly assigned to early (7–12 days) or late (≥8 weeks) ileostomy closure after ileal pouch construction. DESIGN: This was a multicenter, prospective randomized trial. SETTING: The study was conducted at colorectal surgical units at select United States hospitals. PATIENTS: Adults with ulcerative colitis who underwent 2- or 3-stage proctocolectomy with IPAA were included. MAIN OUTCOME MEASURES: The primary outcomes included Comprehensive Complication Index at 30 days after ileostomy closure. The secondary outcomes included complications, severe complications, reoperations, and readmissions within 30 days of ileostomy closure. RESULTS: The trial was stopped after interim analysis because of a high rate of complications after early ileostomy closure. Among 36 patients analyzed, 1 patient (3%) had unplanned proctectomy with end-ileostomy. Of the remaining 35 patients, 28 patients (80%) were clinically eligible for early closure and underwent radiologic assessment. There were 3 radiologic failures. Of the 25 remaining patients, 22 patients (88%) were randomly assigned to early closure (n = 10) or late closure (n = 12), and 3 patients were excluded. Median Comprehensive Complication Index was 14.8 (0–54) and 0 (0–23) after early and late closure ( p = 0.02). One or more complications occurred in 7 patients (70%) after early closure and in 2 patients (17%) after late closure ( p = 0.01)‚ and complications were severe in 3 patients (30%) after early closure and 0 patients after late closure ( p = 0.04). Reoperation was required in 1 patient (10%) and 0 patients ( p = 0.26) after early closure and readmission was required in 7 patients (70%) and 1 patient (8%) after late closure ( p = 0.003). LIMITATIONS: This study was limited by early study closure and selection bias. CONCLUSIONS: Early closure of a diverting ileostomy in patients with ulcerative colitis who underwent IPAA is associated with an unacceptably high rate of complications. See Video Abstract at http://links.lww.com/DCR/C68. ALTA TASA DE COMPLICACIONES DESPUÉS DEL CIERRE PRECOZ DE LA ILEOSTOMÍA: TERMINACIÓN TEMPRANA DEL ENSAYO ALEATORIZADO DE INTERVALO CORTO VERSUS LARGO PARA LA REVERSIÓN DE LA ILEOSTOMÍA EN ASA DESPUÉS DE LA CIRUGÍA DE RESERVORIO ILEAL ANTECEDENTES: En los pacientes con colitis ulcerosa que se someten a una anastomosis del reservorio ileoanal, se utiliza una ileostomía de derivación para disminuir la gravedad de las complicaciones de la anastomosis. Por lo general, la ileostomía se cierra después de un intervalo de 2 a 4 meses. Se desconoce la seguridad del cierre más temprano de la ileostomía después de la cirugía de reservorio. OBJETIVO: Comparar los resultados posoperatorios en pacientes asignados al azar al cierre temprano (7–12 días) o tardío (≥ 8 semanas) de la ileostomía después de la construcción de un reservorio ileal. DISEÑO: Este fue un ensayo aleatorizado prospectivo multicéntrico. ESCENARIO: El estudio se realizó en unidades quirúrgicas colorrectales en hospitales seleccionados de los Estados Unidos. PACIENTES: Se incluyeron adultos con colitis ulcerosa que se sometieron a proctocolectomía en 2 o 3 tiempos con anastomosis ileoanal con reservorio. PRINCIPALES MEDIDAS DE RESULTADO: Los resultados primarios incluyeron el Índice Integral de Complicaciones a los 30 días después del cierre de la ileostomía. Los resultados secundarios incluyeron complicaciones, complicaciones graves, reoperaciones y readmisiones dentro de los 30 días posteriores al cierre de la ileostomía. RESULTADOS: El ensayo se detuvo después del análisis interino debido a una alta tasa de complicaciones después del cierre temprano de la ileostomía. Entre los 36 pacientes analizados, 1 (3%) tuvo una proctectomía no planificada con ileostomía terminal. De los 35 pacientes restantes, 28 (80%) fueron clínicamente elegibles para el cierre temprano y se sometieron a una evaluación radiológica. Hubo 3 fracasos radiológicos. De los 25 pacientes restantes, 22 (88 %) se asignaron al azar a cierre temprano (n = 10) o tardío (n = 12) y 3 fueron excluidos. La mediana del Índice Integral de Complicaciones fue de 14,8 (0–54) y 0 (0–23) después del cierre temprano y tardío ( p = 0,02). Una o más complicaciones ocurrieron en 7 pacientes (70%) después del cierre temprano y 2 (17%) pacientes después del cierre tardío ( p = 0,01) y fueron graves en 3 (30%) y 0 pacientes, respectivamente ( p = 0,04). Requirieron reintervención en 1 (10%) y 0 ( p = 0,26) y reingreso en 7 (70%) y 1 (8%) pacientes ( p = 0,003). LIMITACIONES: Este estudio estuvo limitado por el cierre temprano del estudio; sesgo de selección. CONCLUSIONES: El cierre temprano de una ileostomía de derivación en pacientes con colitis ulcerosa con anastomosis de reservorio ileoanal se asocia con una tasa inaceptablemente alta de complicaciones. Consulte Video Resumen en http://links.lww.com/DCR/C68. (Traducción—Dr. Felipe Bellolio )

Langenfeld, Sean J. M.D.; Davis, Bradley R. M.D.; Vogel, Jon D. M.D.; Davids, Jennifer S. M.D.; Temple, Larissa K.F. M.D.; Cologne, Kyle G. M.D.; Hendren, Samantha M.D.; Hunt, Steven M.D.; Garcia Aguilar, Julio M.D.; Feingold, Daniel L. M.D.; Lightner, Amy L. M.D.; Paquette, Ian M. M.D.; Prepared on behalf of the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons Author Information

BACKGROUND: The benefit of adjuvant therapy is unclear in patients with rectal cancer achieving a pathologic complete response after neoadjuvant chemoradiotherapy and total mesorectal excision. OBJECTIVE: This study aimed to assess the benefit of adjuvant chemotherapy on survival among rectal cancer patients with a pathologic complete response after neoadjuvant chemoradiation. DESIGN: Retrospective cohort study. SETTING: National Cancer Database (2004–2017). PATIENTS: Patients with clinical stage 2 or 3 rectal adenocarcinoma who underwent neoadjuvant chemoradiation (50–50.4 Gy in 25–28 fractions) followed by total mesorectal excision with a pathologic complete response were included. INTERVENTION: Adjuvant chemotherapy. MAIN OUTCOME MEASURES: Overall survival. RESULTS: There were 20,518 patients and 2221 (11%) had a pathologic complete response after neoadjuvant chemoradiation. Of 2221 patients, 1441 (65%) did not receive adjuvant therapy and 780 (35%) did. Patients who received adjuvant therapy were more likely to be younger (median 58 vs 62 y), have private insurance (61% vs 49%), and have node-positive disease (57% vs 48%) (all p < 0.05). There were no differences in sex, race, Charlson-Deyo score, clinical T-stage, tumor size and differentiation, adequate lymphadenectomy (12 or more), or sphincter preservation between groups (all p > 0.05). Overall survival at 5, 10, and 14 years was significantly longer in the adjuvant group (93%, 85%, 83%, respectively) compared to patients who did not receive adjuvant therapy (87%, 67%, 51%, respectively) ( p < 0.001). In a subgroup analysis, adjuvant therapy was associated with improved survival in patients with clinical stage 2 and 3 rectal cancer ( p < 0.001). After adjusting for patient and tumor characteristics, omission of adjuvant chemotherapy was associated with significantly worse survival (HR 1.53, 95% 1.08–2.16). LIMITATIONS: Selection bias, unknown perioperative morbidity, chemotherapy regimen, recurrence status, and other unidentified factors limiting survival analysis. CONCLUSIONS: In patients with clinical stage 2 or 3 rectal cancer, adjuvant chemotherapy was associated with improved overall survival in patients achieving a pathological complete response after neoadjuvant chemoradiotherapy. See Video Abstract at http://links.lww.com/DCR/C139. SOBREVIDA MEJORADA DESPUÉS DE LA TERAPIA ADYUVANTE EN PACIENTES CON CÁNCER DE RECTO LOCALMENTE AVANZADO CON RESPUESTA PATOLÓGICA COMPLETA ANTECEDENTES: En los pacientes con cáncer de recto que logran una respuesta patológica completa después de la quimiorradioterapia neoadyuvante y la escisión total del mesorrecto, el beneficio de la terapia adyuvante no está claro. OBJETIVO: Evaluar el beneficio de la quimioterapia adyuvante en la sobrevida de los pacientes con cáncer de recto con una respuesta patológica completa después de la quimiorradioterapia neoadyuvante. DISEÑO: Estudio de cohorte retrospectivo. ESCENARIO: Base de Datos Nacional de Cáncer (2004-2017). PACIENTES: Pacientes con adenocarcinoma rectal en estadio clínico 2 ó 3 que se sometieron a quimiorradiación neoadyuvante (50-50,4 Gy en 25-28 fracciones) seguida de escisión mesorrectal total con una respuesta patológica completa. INTERVENCIÓN: Quimioterapia adyuvante. PRINCIPALES MEDIDAS DE RESULTADO: Sobrevida global. RESULTADOS: Hubo 20.518 pacientes y 2.221 (11%) tuvieron una respuesta patológica completa después de la quimiorradiación neoadyuvante. Entre estos 2221 pacientes, 1441 (65%) no recibieron terapia adyuvante y 780 (35%) sí. Los pacientes que recibieron terapia adyuvante tenían más probabilidades de ser más jóvenes (mediana de 58 frente a 62 años), tener un seguro privado (61% frente a 49%) y tener enfermedad con linfonodos positivos (57% frente a 48 %) (todos p < 0,05). No hubo diferencias en género, raza, puntuación de Charlson-Deyo, estadio T clínico, tamaño y diferenciación del tumor, linfadenectomía adecuada (≥12) o preservación del esfínter entre los grupos (todos p > 0,05). La sobrevida general a los 5, 10 y 14 años fue significativamente mayor en el grupo adyuvante (93%, 85%, 83%, respectivamente) en comparación con los pacientes que no recibieron terapia adyuvante (87%, 67%, 51% respectivamente) ( p < 0,001). En un análisis de subgrupos, la terapia adyuvante se asoció con una mejor sobrevida general en pacientes con cáncer de recto en estadio clínico 2 y 3 ( p < 0,001). Después de ajustar por las características del paciente y del tumor, la omisión de la quimioterapia adyuvante se asoció con una sobrevida global significativamente peor (HR 1,53, IC del 95%, 1,08–2,16). LIMITACIONES: Sesgo de selección; morbilidad perioperatoria desconocida, régimen de quimioterapia, estado de recurrencia y otros factores no identificados que limitan el análisis de sobrevida. CONCLUSIONES: En pacientes con cáncer de recto en estadio clínico 2 ó 3, la quimioterapia adyuvante se asoció con una mejor sobrevida general en pacientes que lograron una respuesta patológica completa después de la quimiorradioterapia neoadyuvante. Consulte Video Resumen en http://links.lww.com/DCR/C139. (Traducción—Dr. Felipe Bellolio )

85 Background: Rising rates of early-onset colorectal cancer (EOCRC) pose a dilemma for clinicians when deciding how to treat early-stage patients to maximize outcomes. While standard-of-care for Stage II colon cancer is largely surgical resection, evidence suggests that treatment selection may differ by patient age. We sought to determine whether rates of adjuvant chemotherapy administration differ between early and later-onset patients with Stage II CRC. Methods: Data were derived from the Flatiron National Database spanning 1/1/2003 to 8/1/2021. Patients 18 years or older with Stage II CRC were grouped into those aged 18-49 (EOCRC) and those aged 50 or older (LOCRC). Demographic characteristics, ECOG score, stage and site of tumor, and chemotherapy were included for all patients. Primary outcomes of interest included rates of adjuvant chemotherapy administration by age and ethnicity. Univariate and multivariable logistic regression models were used to evaluate relationships between chemotherapy administration, age groups, and ethnicity while adjusting for significant covariates. Results: Of 2133 patients with Stage II CRC, 1606 patients with complete data were included. A secondary analysis of 1065 patients with colon cancer was performed to address potential confounding factors related to neoadjuvant and/or adjuvant chemotherapy given in patients with stage II rectal cancer. Mean age of EOCRC patients was 45.0 years (range: 41.0-48.0) vs. 68.0 years (60.0-75.0) for LOCRC. Adjusting for ethnicity, gender, site, and ECOG score, multivariate analysis showed EOCRC patients received chemotherapy significantly more often than LOCRC patients for stage II CRC (adjusted odds ratio 1.85, 95% CI 1.32-2.60, p < 0.001). Similar findings were observed in the colon cancer only cohort (adjusted OR 2.02, 95% CI 1.31-3.09, p < 0.001). By ethnicity, non-Hispanic patients received chemotherapy at significantly lower rates than Hispanic patients in both cohorts (adjusted odds ratio 0.58, 95% CI 0.39-0.88, p = 0.009 and adjusted odds ratio 0.55, 95% CI 0.34-0.91, p = 0.018). In a subgroup analysis of Stage IIA patients, multivariate logistic regression adjusting for gender, ECOG, site, and ethnicity showed that patients with EOCRC were more likely to receive chemotherapy than patients with LOCRC (adjusted odds ratio 1.91, 95% CI 1.21-2.99, p = 0.005). Updated survival data will be presented. Conclusions: Adjuvant chemotherapy is given preferentially in Stage II EOCRC, even in Stage IIA disease, despite deviation from established guidelines. This may expose patients at low risk for recurrence to unnecessary toxicities and reveals potential provider bias in favor of younger patients in aggressively treating CRC, despite unclear evidence for any outcome benefit.

Department of Surgery, PIH Health, Whittier, CA Funding/Support: None reported. Financial Disclosure: None reported.