Preoperative Treatment of Locally Advanced Rectal Cancer.

BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer.

Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR] = 0.3 in the targeted sequencing and OR = 0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR = 6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, non-responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.

Tumour budding as a prognostic biomarker in biopsies and resections of neoadjuvant-treated rectal adenocarcinoma.

BACKGROUND: Tumour budding (TB) is a marker of tumour aggressiveness which, when measured in rectal cancer resection specimens, predicts worse outcomes and response to neoadjuvant therapy. We investigated the utility of TB assessment in the setting of neoadjuvant treatment. METHODS AND RESULTS: A single-centre, retrospective cohort study was conducted. TB was assessed using the hot-spot International Tumour Budding Consortium (ITBCC) method and classified by the revised ITBCC criteria. Haematoxylin and eosin (H&E) and AE1/AE3 cytokeratin (CK) stains for ITB (intratumoural budding) in biopsies with PTB (peritumoural budding) and ITB (intratumoural budding) in resection specimens were compared. Logistic regression assessed budding as predictors of lymph node metastasis (LNM). Cox regression and Kaplan-Meier analyses investigated their utility as a predictor of disease-free (DFS) and overall (OS) survival. A total of 146 patients were included; 91 were male (62.3%). Thirty-seven cases (25.3%) had ITB on H&E and 79 (54.1%) had ITB on CK assessment of biopsy tissue. In univariable analysis, H&E ITB [odds (OR) = 2.709, 95% confidence interval (CI) = 1.261-5.822, P = 0.011] and CK ITB (OR = 2.165, 95% CI = 1.076-4.357, P = 0.030) predicted LNM. Biopsy-assessed H&E ITB (OR = 2.749, 95% CI = 1.258-6.528, P = 0.022) was an independent predictor of LNM. In Kaplan-Meier analysis, ITB identified on biopsy was associated with worse OS (H&E, P = 0.003, CK: P = 0.009) and DFS (H&E, P = 0.012; CK, P = 0.045). In resection specimens, CK PTB was associated with worse OS (P = 0.047), and both CK PTB and ITB with worse DFS (PTB, P = 0.014; ITB: P = 0.019). In multivariable analysis H&E ITB predicted OS (HR = 2.930, 95% CI = 1.261-6.809) and DFS (HR = 2.072, 95% CI = 1.031-4.164). CK PTB grading on resection also independently predicted OS (HR = 3.417, 95% CI = 1.45-8.053, P = 0.005). CONCLUSION: Assessment of TB using H&E and CK may be feasible in rectal cancer biopsy and post-neoadjuvant therapy-treated resection specimens and is associated with LNM and worse survival outcomes. Future management strategies for rectal cancer might be tailored to incorporate these findings.

Outcomes Following Pelvic Exenteration for Locally Recurrent Rectal Cancer With and Without En Bloc Sacrectomy.

BACKGROUND: Extended radical resection is often the only chance of cure for locally recurrent rectal cancer. Recurrence in the posterior compartment often necessitates en bloc sacrectomy as part of pelvic exenteration to obtain clear resection margins and provide survival benefit. OBJECTIVE: To compare oncological outcomes, morbidity, and quality-of-life outcomes following pelvic exenteration with and without en bloc sacrectomy for recurrent rectal cancer. DESIGN: Comparative cohort study with retrospective analysis of prospectively collected data. SETTING: This study was conducted at a high-volume pelvic exenteration center. PATIENTS: Patients who underwent pelvic exenteration for locally recurrent rectal cancer between 1994 and 2022. MAIN OUTCOME MEASURES: Overall survival, postoperative morbidity, R0 resection margin, and quality-of-life outcomes. RESULTS: Of 965 patients, 305 (31.6%) underwent pelvic exenteration for locally recurrent rectal cancer. Among these patients, 64.3% were men and the median age was 62 years (range, 29-86). One hundred eighty-five patients (60.7%) underwent en bloc sacrectomy, 65 (35.1%) underwent high transection, and 119 (64.3%) had sacrectomy below S2. R0 resection was achieved in 80% of patients with sacrectomy and 72.5% of patients without sacrectomy. Sacrectomy patients experienced more postoperative complications without increased mortality. The median overall survival was 52 months; median survival was 47 months with sacrectomy and 73 months without ( p = 0.059). Quality-of-life scores were not significantly different across physical component ( p = 0.346), mental component ( p = 0.787), or Functional Assessment of Cancer Therapy-Colorectal ( p = 0.679) scores at 24-month follow-up. LIMITATIONS: The generalizability of these findings may be limited outside of subspecialist exenteration units. Selection bias exists in a retrospective analysis. CONCLUSIONS: Patients undergoing pelvic exenteration with and without en bloc sacrectomy for locally recurrent rectal cancer experience similar rates of R0 resection, survival, and quality-of-life outcomes. As R0 remains the most important predictor of survival, the requirement of sacral resection should prompt referral to a subspecialist center that performs sacrectomy routinely. See Video Abstract . RESULTADOS DESPUS DE LA EXENTERACIN PLVICA PARA EL CNCER DE RECTO CON RECURRENCIA LOCAL, CON Y SIN SACRECTOMA EN BLOQUE: ANTECEDENTES:La resección radical ampliada es generalmente la única posibilidad de curación para el cáncer de recto con recurrencia local. La recurrencia en el compartimento posterior generalmente requiere sacrectomía en bloque como parte de la exenteración pélvica para obtener márgenes de resección claros y proporcionar un beneficio de supervivencia.OBJETIVO:Comparar los resultados oncológicos, de morbilidad y de calidad de vida después de la exenteración pélvica con y sin sacrectomía en bloque para el cáncer de recto recurrente.DISEÑO:Estudio de cohorte comparativo con análisis retrospectivo de datos recopilados prospectivamente.AMBIENTE AJUSTE:Estudio realizado en un centro de exenteración pélvica de alto volumen.PACIENTES:Aquellos sometidos a exenteración pélvica por cáncer de recto con recurrencia local entre 1994 y 2022.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia general, morbilidad posoperatoria, margen de resección R0 y resultados de calidad de vida.RESULTADOS:305 (31,6%) de 965 pacientes se sometieron a exenteración pélvica por cáncer de recto con recurrencia local. El 64,3% de los pacientes eran hombres con una mediana de edad de 62 años (rango 29-86). 185 pacientes (60,7%) fueron sometidos a sacrectomía en bloque, 65 (35,1%) fueron sometidos a transección alta, 119 (64,3%) tuvieron sacrectomía por debajo de S2. La resección R0 se logró en el 80% de los pacientes con sacrectomía y en el 72,5% sin ella. Los pacientes de sacrectomía experimentaron más complicaciones postoperatorias sin aumento de la mortalidad. La mediana de supervivencia global fue de 52 meses, 47 meses con sacrectomía y 73 meses sin sacrectomía ( p = 0,059). Las puntuaciones de calidad de vida no fueron significativamente diferentes entre las puntuaciones del componente físico ( p = 0,346), componente mental ( p = 0,787) o la evaluación funcional de la terapia contra el cáncer - colorrectal ( p = 0,679) a los 24 meses de seguimiento.LIMITACIONES:La generalización de estos hallazgos puede estar limitada fuera de las unidades de exenteración de subespecialistas. Existe un sesgo de selección en un análisis retrospectivo.CONCLUSIONES:Los pacientes sometidos a exenteración pélvica con y sin sacrectomía en bloque por cáncer de recto con recurrencia local experimentan tasas similares de resección R0, supervivencia y resultados de calidad de vida. Como R0 sigue siendo el predictor más importante de supervivencia, la necesidad de resección sacra debe provocar la derivación a un centro subespecialista que realice sacrectomía de forma rutinaria. (Traducción-Dr. Fidel Ruiz Healy ).

Local Excision Versus Radical Resection for Grade 2 Rectal Neuroendocrine Tumors: A Multicenter Propensity Score-Matched Analysis.

BACKGROUND: Studies on grade 2 rectal neuroendocrine tumors are limited, and the optimal treatment for these tumors is not well established. OBJECTIVE: We aimed to compare the oncologic results of local excision versus radical resection for the treatment of grade 2 rectal neuroendocrine tumors. DESIGN: Retrospective multicenter propensity score-matched study to minimize heterogeneity between groups and focus on the differences between surgery strategies. SETTINGS: Seventeen large-scale Chinese medical centers participated in this study. PATIENTS: A total of 144 patients with pathologically confirmed grade 2 rectal neuroendocrine tumors were retrospectively analyzed. MAIN OUTCOME MEASURES: Cancer-specific survival and relapse-free survival were assessed to compare surgery strategies. RESULTS: A total of 144 patients with grade 2 rectal neuroendocrine tumors were enrolled in this study. Twenty-seven patients underwent endoscopic resection, 55 underwent transanal excision, 50 underwent radical resection, and 12 underwent palliative surgery or biopsy for distant metastasis. Of the 50 patients who underwent radical resection, 30 (60.0%) had clinically positive lymph nodes on the basis of the histopathology results. The optimal cutoff value for tumor size to predict cancer-specific survival was 1.5 cm. In patients with grade 2 rectal neuroendocrine tumors of ≤1.5-cm size, there were no significant differences in cancer-specific survival and relapse-free survival between local excision and radical resection groups ( p > 0.05). In patients with grade 2 rectal neuroendocrine tumors of >1.5-cm size, relapse-free survival was significantly lower in the local excision group than in the radical resection group ( p = 0.04). LIMITATIONS: The nature of retrospective reviews and a relatively short follow-up period are limitations of this study. CONCLUSIONS: Grade 2 rectal neuroendocrine tumors have a nonnegligible rate of lymph node metastasis. Local excision is a feasible choice for tumors of ≤1.5 cm size without metastasis, whereas radical resection is more beneficial in those of >1.5 cm size. See Video Abstract . ESCISIN LOCAL VERSUS RESECCIN RADICAL PARA TUMORES NEUROENDOCRINOS RECTALES GRADO ANLISIS MULTICNTRICO CON PUNTUACIN DE PROPENSIN COINCIDENTE: ANTECEDENTES:Los estudios sobre los tumores neuroendocrinos rectales de grado 2 son limitados y el tratamiento óptimo para estos tumores no está bien establecido.OBJETIVO:Comparar los resultados oncológicos de la escisión local versus la resección radical para el tratamiento de tumores neuroendocrinos rectales grado 2.DISEÑO:Estudio multicéntrico retrospectivo emparejado por puntuación de propensión para minimizar la heterogeneidad entre grupos y centrarse en la diferencia entre estrategias quirúrgicas.ESCENARIO:Diecisiete centros médicos chinos de gran tamaño participaron en este estudio.PACIENTES:Se analizaron retrospectivamente un total de 144 pacientes con tumores neuroendocrinos rectales grado 2 patológicamente confirmados.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron la supervivencia específica del cáncer y la supervivencia libre de recaída para comparar las estrategias quirúrgicas.RESULTADOS:En este estudio se inscribieron un total de 144 pacientes con tumores neuroendocrinos rectales grado 2. Veintisiete pacientes se sometieron a resección endoscópica, 55 a escisión transanal, 50 a resección radical y 12 a cirugía paliativa o biopsia por metástasis a distancia. De los 50 pacientes que se sometieron a resección radical, 30 (60,0%) tenían ganglios linfáticos clínicamente positivos según los resultados histopatológicos. El valor de corte óptimo para el tamaño del tumor para predecir la supervivencia específica del cáncer fue de 1,5 cm. En pacientes con tumores neuroendocrinos rectales grado 2 ≤ 1,5 cm, no hubo diferencias significativas en la supervivencia específica del cáncer y la supervivencia libre de recaída entre los grupos de escisión local y resección radical ( p >0,05). En pacientes con tumores neuroendocrinos rectales grado 2 > 1,5 cm, la supervivencia libre de recaída fue significativamente menor en el grupo de escisión local que en el grupo de resección radical ( p = 0,04).LIMITACIONES:La naturaleza de la revisión retrospectiva y el período de seguimiento relativamente corto son limitaciones de este estudio.CONCLUSIONES:Los tumores neuroendocrinos rectales grado 2 tienen una tasa no despreciable de metástasis en los ganglios linfáticos. La escisión local es una opción factible para tumores ≤ 1,5 cm sin metástasis, mientras que la resección radical es más beneficiosa en aquellos > 1,5 cm. (Traducción-Dr. Felipe Bellolio ).

Rectal Cancer Survival for Residual Carcinoma In Situ Versus Pathologic Complete Response After Neoadjuvant Therapy.

BACKGROUND: Pathologic complete response after neoadjuvant chemoradiotherapy for rectal cancer is associated with improved survival. It is unclear whether residual carcinoma in situ portends a similar outcome. OBJECTIVE: To compare the survival of patients with locally advanced rectal cancer who received neoadjuvant therapy and achieved pathologic carcinoma in situ versus pathologic complete response. DESIGN: Retrospective cohort study. SETTING: National public database. PATIENTS: A total of 4594 patients in the National Cancer Database from 2006 to 2016 with locally advanced rectal cancer who received neoadjuvant therapy, underwent surgery, and had node-negative ypTis or ypT0 on final pathology were included. Of these, 4321 patients (94.1%) had ypT0 and 273 (5.9%) had ypTis on final pathology. MAIN OUTCOME MEASURE: Overall survival. RESULTS: The median age was 60 years, and 1822 patients (39.7%) were women. On initial staging, 54.5% (n = 2503) had stage II disease and 45.5% (n = 2091) had stage III disease. The ypTis group had decreased overall survival compared to the ypT0 group (HR 1.42; 95% CI, 1.04-1.95; p = 0.028). Other factors associated with decreased overall survival were older age at diagnosis, increasing Charlson-Deyo score, and poorly differentiated tumor grade. Variables associated with improved survival were female sex, private insurance, and receipt of both neoadjuvant and adjuvant chemotherapy. For the total cohort, there was no difference in survival between clinical stage II and stage III. LIMITATIONS: Standard therapy versus total neoadjuvant therapy could not be abstracted. Overall survival was defined as the time from surgery to death from any cause or last contact, allowing for some erroneously misclassified deaths. CONCLUSIONS: ypTis is associated with worse overall survival than ypT0 for patients with locally advanced rectal cancer who receive neoadjuvant chemoradiotherapy followed by surgery. For this cohort, clinical stage was not a significant predictor of survival. Prospective trials comparing survival for these pathologic outcomes are needed. See Video Abstract . SUPERVIVENCIA DEL CNCER DE RECTO PARA EL CARCINOMA RESIDUAL IN SITU VS RESPUESTA PATOLGICA COMPLETA DESPUS DE LA TERAPIA NEOADYUVANTE: ANTECEDENTESLa respuesta patológica completa después de la quimiorradioterapia neoadyuvante para el cáncer de recto se asocia con una mayor supervivencia. No está claro si el carcinoma residual in situ presagia un resultado similar.OBJETIVOComparar la supervivencia de pacientes con cáncer de recto localmente avanzado que recibieron terapia neoadyuvante y lograron un carcinoma patológico in situ versus una respuesta patológica completa.DISEÑOEstudio de cohorte retrospectivo.ESCENARIOBase de datos pública nacional.PACIENTESSe incluyeron 4,594 pacientes de la Base de Datos Nacional de Cáncer de 2006 a 2016 con cáncer de recto localmente avanzado que recibieron terapia neoadyuvante, fueron sometidos a cirugía y tuvieron ganglios negativos, ypTis o ypT0 en el reporte patológico final. 4.321 (94,1%) tuvieron ypT0 y 273 (5,9%) tuvieron ypTis en el reporte final.PRINCIPALES MEDIDAS DE RESULTADOSupervivencia general.RESULTADOSLa mediana de edad fue de 60 años. 1.822 pacientes (39,7%) fueron mujeres. El 54,5% (n = 2.503) tuvo la enfermedad en estadio II y el 45,5% (n = 2.091) tuvo la enfermedad en estadio III según la estadificación inicial. El grupo ypTis tuvo una supervivencia general reducida en comparación con el grupo ypT0 (HR 1,42, IC 95 % 1,04-1,95, p = 0,028). Otros factores asociados con una menor supervivencia general fueron una edad más avanzada al momento del diagnóstico, un aumento de la puntuación de Charlson-Deyo y un grado tumoral poco diferenciado. Las variables asociadas con una mejor supervivencia fueron el sexo femenino, el seguro privado y la recepción de quimioterapia neoadyuvante y adyuvante. Para la cohorte total, no hubo diferencias en la supervivencia entre el estadio clínico 2 y el estadio 3.LIMITACIONESNo se pudo resumir el tratamiento estándar versus el tratamiento neoadyuvante total. La supervivencia general se definió como el tiempo transcurrido desde la cirugía hasta la muerte por cualquier causa o último contacto, lo que permite algunas muertes erróneamente clasificadas.CONCLUSIONESypTis se asocia con una peor supervivencia general que ypT0 en pacientes con cáncer de recto localmente avanzado que reciben quimiorradioterapia neoadyuvante seguida de cirugía. Para esta cohorte, el estadio clínico no fue un predictor significativo de supervivencia. Se necesitan ensayos prospectivos que comparen la supervivencia de estos resultados patológicos. ( Traducción-Dr Osvaldo Gauto ).

The Enigma That is Rectal Squamous Cell Carcinoma: A Case Series.

INTRODUCTION: Colorectal cancer is the third most common cancer and the third leading cause of cancer deaths in the United States. As rectal squamous cell carcinoma (SCC) is an uncommon colorectal cancer, there is limited data on this clinical entity. We aimed to evaluate the tumor characteristics, treatment, and clinical outcomes of this rare deadly disease. METHODS: Pathological specimens from 2017 to 2022 at a single National Cancer Institute-designated cancer center were screened for all rectal cases with a diagnosis of SCC. All patients with a primary rectal SCC were included. Patients who had extension to the dentate line or evidence of an anal mass, and those who were treated at an outside institution, were excluded. Demographic, treatment, outcome, and surveillance data was extracted. RESULTS: There were 56 specimens identified, nine of which met inclusion criteria. Most patients were White (78%), Hispanic (78%), and female (67%). The average age at diagnosis was 57 y [52-65]. All patients had nodal involvement at the time of clinical staging. All patients were treated with Nigro protocol, with one patient treated with surgery first. The median time of follow-up was 12 mo after initial treatment, 33% had recurrence, with median time to recurrence of 25 mo. Overall, mortality from rectal SCC was 33% at a median time of 37 mo from initial diagnosis. CONCLUSIONS: Rectal SCC is a colorectal cancer that is not fully understood. Our findings showed that treatment mirrors that of anal SCC, with similar rates of survival to both rectal adenocarcinoma and anal SCC.

Association of Surgical Approaches and Outcomes in Total Mesorectal Excision and Margin Status for Rectal Cancer.

INTRODUCTION: Despite being a key metric with a significant correlation with the outcomes of patients with rectal cancer, the optimal surgical approach for total mesorectal excision (TME) has not yet been identified. The aim of this study was to assess the association of the surgical approach on the quality of TME and surgical margins and to characterize the surgical and long-term oncologic outcomes in patients undergoing robotic, laparoscopic, and open TME for rectal cancer. METHODS: Patients with primary, nonmetastatic rectal adenocarcinoma who underwent either lower anterior resection or abdominoperineal resection via robotic (Rob), laparoscopic (Lap), or open approaches were selected from the US Rectal Cancer Consortium database (2007-2017). Quasi-Poisson regression analysis with backward selection was used to investigate the relationship between the surgical approach and outcomes of interest. RESULTS: Among the 664 patients included in the study, the distribution of surgical approaches was as follows: 351 (52.9%) underwent TME via the open approach, 159 (23.9%) via the robotic approach, and 154 (23.2%) via the laparoscopic approach. There were no significant differences in baseline demographics among the three cohorts. The laparoscopic cohort had fewer patients with low rectal cancer (<6 cm from the anal verge) than the robotic and open cohorts (Lap 28.6% versus Rob 59.1% versus Open 45.6%, P = 0.015). Patients who underwent Rob and Lap TME had lower intraoperative blood loss compared with the Open approach (Rob 200 mL [Q1, Q3: 100.0, 300.0] versus Lap 150 mL [Q1, Q3: 75.0, 250.0] versus Open 300 mL [Q1, Q3: 150.0, 600.0], P < 0.001). There was no difference in the operative time (Rob 243 min [Q1, Q3: 203.8, 300.2] versus Lap 241 min [Q1, Q3: 186, 336] versus Open 226 min [Q1, Q3: 178, 315.8], P = 0.309) between the three approaches. Postoperative length of stay was shorter with robotic and laparoscopic approach compared to open approach (Rob 5.0 d [Q1, Q3: 4, 8.2] versus Lap 5 d [Q1, Q3: 4, 8] versus Open 7.0 d [Q1, Q3: 5, 9], P < 0.001). There was no statistically significant difference in the quality of TME between the robotic, laparoscopic, and open approaches (79.2%, 64.9%, and 64.7%, respectively; P = 0.46). The margin positivity rate, a composite of circumferential margin and distal margin, was higher with the robotic and open approaches than with the laparoscopic approach (Rob 8.2% versus Open 6.6% versus Lap 1.9%, P = 0.17), Rob versus Lap (odds ratio 0.21; 95% confidence interval 0.05, 0.83) and Rob versus Open (odds ratio 0.5; 95% confidence interval 0.22, 1.12). There was no difference in long-term survival, including overall survival and recurrence-free survival, between patients who underwent robotic, laparoscopic, or open TME (Figure 1). CONCLUSIONS: In patients undergoing surgery with curative intent for rectal cancer, we did not observe a difference in the quality of TME between the robotic, laparoscopic, or open approaches. Robotic and open TME compared to laparoscopic TME were associated with higher margin positivity rates in our study. This was likely due to the higher percentage of low rectal cancers in the robotic and open cohorts. We also reported no significant differences in overall survival and recurrence-free survival between the aforementioned surgical techniques.

Evaluation of the prognostic impact of pathologic tumor regression grade on patients with colorectal cancer after preoperative chemoradiotherapy.

BACKGROUND: The prognostic value of the pathological response to preoperative chemoradiotherapy (CRT) in rectal cancer (RC) remains unknown. OBJECTIVES: We aimed to assess the predictive value of the response to CRT that was derived from an evaluation of the histological findings (whole-section vs. representative-section sampling) and attempted to determine an objective cut-off value for the tumor regression grade (TRG). METHODS: We examined the association of the TRG with the outcomes (recurrence-free survival [RFS] and overall survival [OS]) of 78 patients with RC. Patients with RC treated with preoperative CRT were divided into development (30 cases) and validation (48 cases) cohorts. The TRG was classified as grades I (Ia, Ib), II, and III. The cut-off value was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: The TRG determined from whole-section sampling versus representative-section sampling was more strongly correlated with patient survival. We found that in both cohorts, patients with a cut-off value of <73% had a poor prognosis. Finally, the cut-off value was found to be an independent predictive factor in both univariate and multivariate analysis. CONCLUSIONS: The TRG that was used to evaluate patients with RC who underwent preoperative CRT was an independent prognostic factor for outcome.

Effect of neoadjuvant therapy regimens on lymph nodes yield in rectal cancer.

BACKGROUND AND OBJECTIVES: Pathological nodal staging is relevant to postoperative decision-making and a prognostic marker of cancer survival. This study aimed to assess the effect of different total neoadjuvant therapy (TNT) regimens on lymph node status following total mesorectal excision (TME) for locally advanced rectal cancer (LARC). METHODS: A retrospective cohort study of patients treated for node-positive clinical stage 3 LARC with TNT between January 2015 and August 2022. Patients were stratified into induction therapy and consolidation therapy groups. Variables collated included patient demographics, clinical and radiological characteristics of the tumor, and pathology of the resected specimen. Primary outcome was total harvested lymph nodes. RESULTS: Ninety-seven patients were included (57 [58.8%] males; mean age of 58.5 ± 11.4 years). The induction therapy group included 85 (87.6%) patients while 12 (12.4%) patients received consolidation therapy. A median interquartile range value of 22.00 (5.00-72.00) harvested lymph nodes was recorded for the induction therapy group in comparison to 16.00 (16.00-47.00) in the consolidation therapy arm (p = 0.487). Overall pathological complete response rate was 34%. CONCLUSION: Total harvested nodes from resected specimens were marginally lower in the consolidation therapy group. Induction therapy may be preferrable to optimize postoperative specimen staging.

Outcomes of rectal cancer patients who refuse surgery after incomplete clinical response to neoadjuvant therapy.

BACKGROUND AND OBJECTIVES: Total mesorectal excision (TME) remains the standard of care for patients with rectal cancer who have an incomplete response to total neoadjuvant therapy (TNT). A minority of patients will refuse curative intent resection. The aim of this study is to examine the outcomes for these patients. METHODS: A retrospective cohort study of stage 1-3 rectal adenocarcinoma patients who underwent neoadjuvant chemoradiation therapy or TNT at a single institution. Patients either underwent TME, watch-and-wait protocol, or if they refused TME, were counseled and watched (RCW). Clinical outcomes and resource utilization were examined in each group. RESULTS: One hundred seventy-one patients (Male 59%) were included with a median surveillance of 43 months. Twenty-nine patients (17%) refused TME and had shortened overall survival (OS). Twelve patients who refused TME converted to a complete clinical response (cCR) on subsequent staging with a prolonged OS. 92% of these patients had a near cCR at initial staging endoscopy. Increased physician visits and testing was utilized in RCW and WW groups. CONCLUSION: A significant portion of patients convert to cCR and have prolonged OS. Lengthening the time to declare cCR may be considered in select patients, such as those with a near cCR at initial endoscopic staging.

Impact of tumor size on overall survival and cancer-specific survival of early-onset colon and rectal cancer: a retrospective cohort study.

PURPOSE: This study aimed to investigate the impact of tumor size on survival in early-onset colon and rectal cancer. METHODS: Early-onset colon and rectal cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Tumor size was analyzed as both continuous and categorical variables. Several statistical techniques, including restricted cubic spline (RCS), Cox proportional hazard model, subgroup analysis, propensity score matching (PSM), and Kaplan-Meier survival analysis, were employed to demonstrate the association between tumor size and overall survival (OS) and cancer-specific survival (CSS) of early-onset colon and rectal cancer. RESULTS: Seventeen thousand five hundred fifty-one (76.7%) early-onset colon and 5323 (23.3%) rectal cancer patients were included. RCS analysis confirmed a linear association between tumor size and survival. Patients with a tumor size > 5 cm had worse OS and CSS, compared to those with a tumor size ≤ 5 cm for both early-onset colon and rectal cancer. Notably, subgroup analysis showed that a smaller tumor size (≤ 50 mm) was associated with worse survival in stage II early-onset colon cancer, although not statistically significant. After PSM, Kaplan-Meier survival curves showed that the survival of patients with tumor size ≤ 50 mm was better than that of patients with tumor size > 50 mm. CONCLUSION: Patients with tumors larger than 5 cm were associated with worse survival in early-onset colon and rectal cancer. However, smaller tumor size may indicate a more biologically aggressive phenotype, correlating with poorer survival in stage II early-onset colon cancer.

Impact of adjuvant chemotherapy on survival after pathological complete response in rectal cancer: a meta-analysis of 31,558 patients.

BACKGROUND: Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a complete pathological response (pCR) is a strong indicator of a positive prognosis, the specific benefits of adjuvant chemotherapy after pCR remain unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to assess the potential advantages of adjuvant therapy in patients who achieve pCR. METHODS: In this study, we searched Medline, Embase, and Web of Science databases for relevant research. We focused on binary outcomes, analyzing them using odds ratios (ORs) with 95% confidence intervals (CIs). To account for potential variability between studies, all endpoints were analyzed with DerSimonian and Laird random-effects models. We assessed heterogeneity using the I2 statistic and employed the R statistical software (version 4.2.3) for all analyses. RESULTS: Thirty-four studies, comprising 31,558 patients, were included. The outcomes demonstrated a significant difference favoring the AC group in terms of overall survival (OS) (HR 0.75; 95% CI 0.60-0.94; p = 0.015; I2 = 0%), and OS in 5 years (OR 1.65; 95% CI 1.21-2.24; p = 0.001; I2 = 39%). There was no significant difference between the groups for disease-free survival (DFS) (HR 0.94; 95% CI 0.76-1.17; p = 0.61; I2 = 17%), DFS in 5 years (OR 1.19; 95% CI 0.82-1.74; p = 0.36; I2 = 43%), recurrence-free survival (RFS) (HR 1.10; 95% CI 0.87-1.40; p = 0.39; I2 = 0%), and relapse-free survival (OR 1.08; 95% CI 0.78-1.51; p = 0.62; I2 = 0%). CONCLUSION: This systematic review and meta-analysis found a significant difference in favor of the ACT group in terms of survival after pCR. Therefore, the administration of this treatment as adjuvant therapy should be encouraged in clinical practice.

Prognostic analysis of rectal cancer patients after neoadjuvant chemoradiotherapy: different prognostic factors in patients with different TRGs.

PURPOSE: The extent of tumor regression varies widely among locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME). The purpose of this retrospectively study is to assess prognostic factors in LARC patients with NCRT, and further to analyze survival outcomes in patients with different tumor regression grades (TRGs). METHODS: This study includes LARC patients who underwent NCRT and TME at our institution. We retrospectively analyzed the clinicopathological characteristics and survival of all patients, and performed subgroup analysis for patients with different TRGs. Survival differences were compared using the Kaplan-Meier method and the log rank test. Additionally, a multiple Cox proportional hazard model was used to identify independent prognostic factors. RESULTS: The study included 393 patients, with 21.1%, 26.5%, 45.5%, and 6.9% achieving TRG 0, TRG 1, TRG 2, and TRG 3, respectively. The overall survival (OS) rate and disease-free survival (DFS) rate for all patients were 89.4% and 70.7%, respectively. Patients who achieved TRG 0-3 had different 5-year OS rates (96.9%, 91.1%, 85.2%, and 68.8%, P = 0.001) and 5-year DFS rates (80.8%, 72.4%, 67.0%, 55.8%, P = 0.031), respectively. Multivariate analyses showed that the neoadjuvant rectal (NAR) score was an independent prognostic indicator for both overall survival (OS) (HR = 4.040, 95% CI = 1.792-9.111, P = 0.001) and disease-free survival (DFS) (HR = 1.971, 95% CI = 1.478-2.628, P ˂ 0.001). In the subgroup analyses, the NAR score was found to be associated with DFS in patients with TRG 1 and TRG 2. After conducting multivariate analysis, it was found that ypT stage was a significant predictor of DFS for TRG 1 patients (HR = 4.384, 95% CI = 1.721-11.168, P = 0.002). On the other hand, ypN stage was identified as the dominant prognostic indicator of DFS for TRG 2 patients (HR = 2.795, 95% CI = 1.535-5.091, P = 0.001). However, none of these characteristics was found to be correlated with survival in patients with TRG 0 or TRG 3. CONCLUSION: NAR score, in particular, appears to be the most powerful prognostic factor. It is important to consider various prognostic predictors for patients with different TRGs.

MRI-defined T3, clear mesorectal fascia mid-low rectal cancer: is neoadjuvant treatment necessary?

AIM: Neoadjuvant treatments (nCRT) are becoming the standard treatment for patients with stage II or III mid-low rectal cancer. Recently, some studies have shown that surgery alone may be sufficient for patients with T3 rectal cancer. This raises the question of whether nCRT is necessary for all patients with T3 rectal cancer. Therefore, this study compared the clinical outcomes of patients with MRI-defined T3, clear MRF mid-low rectal cancer treated with surgery alone (TME group) or nCRT followed by surgery (nCRT + TME group). METHODS: A total of 1509 patients were enrolled in this study. After a 1:1 propensity score matching analysis, 480 patients were included in each group. The primary endpoint was 3-year disease-free survival (DFS). The secondary endpoints included the perioperative outcomes, histopathologic outcomes, and other follow-up outcomes. RESULTS: nCRT had advantages in rates of sphincter-preserving surgery and tumor downstaging, but it was accompanied by a higher rate of enterostomies. At 3 years after surgery, local recurrence occurred in 3.3% of patients in the TME group and in 3.5% of patients in the nCRT + TME group (P = 0.914), the DFS rates were 78.3% in the TME group and 75.3% in the nCRT + TME group (P = 0.188), and the overall survival rates were 90.3% in the TME group and 89.9% in the nCRT + TME group (P = 0.776). CONCLUSIONS: Surgery alone versus nCRT followed by surgery may provide similar long-term oncological outcomes for patients with MRI-defined T3, clear MRF, and mid-low rectal cancer. nCRT may cause overtreatment in some patients.

Construction of a nomogram based on clinicopathologic features to predict the likelihood of No. 253 lymph node metastasis in rectal cancer patients.

PURPOSE: To explore the high-risk factors for rectal cancer No.253 lymph node metastasis (LNM) and to construct a risk nomogram for the individualized prediction of No.253 LNM. METHODS: This was a retrospective analysis of 425 patients with rectal cancer who underwent laparoscopic-assisted radical surgery. Independent risk factors for rectal cancer No.253 LNM was identified using multivariate logistic regression analysis, and a risk prediction nomogram was constructed based on the independent risk factors. In addition, the performance of the model was evaluated by discrimination, calibration, and clinical benefit. RESULTS: Multivariate logistic regression analysis showed that No.253 lymphadenectasis on CT (OR 10.697, P < 0.001), preoperative T4-stage (OR 4.431, P = 0.001), undifferentiation (OR 3.753, P = 0.004), and preoperative Ca199 level > 27 U/ml (OR 2.628, P = 0.037) were independent risk factors for No.253 LNM. A nomogram was constructed based on the above four factors. The calibration curve of the nomogram was closer to the ideal diagonal, indicating that the nomogram had a better fitting ability. The area under the ROC curve (AUC) was 0.865, which indicated that the nomogram had high discriminative ability. In addition, decision curve analysis (DCA) showed that the model could show better clinical benefit when the threshold probability was between 1% and 50%. CONCLUSION: Preoperative No.253 lymphadenectasis on CT, preoperative T4-stage, undifferentiation, and elevated preoperative Ca199 level were found to be independent risk factors for the No.253 LNM. A predictive model based on these risk factors can help surgeons make rational clinical decisions.

Modified neoadjuvant rectal score as a novel prognostic model for rectal cancer patients who underwent chemoradiotherapy.

BACKGROUND: The neoadjuvant rectal score (NAR score) has recently been proposed as a better prognostic model than the conventional TNM classification for rectal cancer patients that have undergone neoadjuvant chemoradiotherapy. We recently developed an apoptosis-detection technique for assessing the viability of residual tumors in resected specimens after chemoradiotherapy. This study aimed to establish an improved prognostic classification by combining the NAR score and the assessment of the apoptosis of residual cancer cells. METHODS: We retrospectively enrolled 319 rectal cancer patients who underwent chemoradiotherapy followed by radical surgery. The recurrence-free survival and overall survival of the four models were compared: TNM stage, NAR score, modified TNM stage by re-staging according to cancer cell viability, and modified NAR score also by re-staging. RESULTS: Downstaging of the ypT stage was observed in 15.5% of cases, whereas only 4.5% showed downstaging of ypN stage. C-index was highest for the modified NAR score (0.715), followed by the modified TNM, TNM, and NAR score. Similarly, Akaike's information criterion was smallest in the modified NAR score (926.2), followed by modified TNM, TNM, and NAR score, suggesting that the modified NAR score was the best among these four models. The overall survival results were similar: C-index was the highest (0.767) and Akaike's information criterion was the smallest (383.9) for the modified NAR score among the four models tested. CONCLUSION: We established a novel prognostic model, for rectal cancer patients that have undergone neoadjuvant chemoradiotherapy, using a combination of apoptosis-detecting immunohistochemistry and neoadjuvant rectal scores.

Prolonged interval to surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A meta-analysis of randomized controlled trials.

BACKGROUND: Long-course neoadjuvant chemoradiotherapy (NCRT), followed by surgery after an interval of 6-8 weeks, represents standard of care for patients with locally advanced rectal cancer (LARC). Increasing this interval may improve rates of complete pathological response (pCR) and tumour downstaging. We performed a meta-analysis comparing standard (SI, within 8 weeks) versus longer (LI, after 8 weeks) interval from NCRT to surgery. METHODS: PubMed, Embase, and Cochrane databases were searched up to 31 August 2022. Randomized controlled trials (RCTs) comparing SI with LI after NCRT for LARC were included. The primary endpoint was pCR rate. Secondary endpoints included rates of R0 resection, circumferential resection margin positivity (+CRM), TME completeness, lymph node yield (LNY), operative duration, tumour downstaging (TD), sphincter preservation, mortality, postoperative complications, surgical site infection (SSI) and anastomotic leak (AL). Random effects models were used to calculate pooled effect size estimates. RESULTS: Four RCTs encompassing 867 patients were included. There were 539 males (62.1%). LI was associated with a higher pCR rate (OR 0.61, 95%CI â€‹= â€‹0.39-0.95, p â€‹= â€‹0.03), and more TD (OR 0.60, 95%CI â€‹= â€‹0.37-0.97, p â€‹= â€‹0.04) compared to SI. However, there was no difference in rates of R0 resection (p â€‹= â€‹0.87), +CRM (p â€‹= â€‹0.66), sphincter preservation (p â€‹= â€‹0.26), incomplete TME (p â€‹= â€‹0.49), LNY (p â€‹= â€‹0.55), SSI (p â€‹= â€‹0.33), AL (p â€‹= â€‹0.20), operative duration (p â€‹= â€‹0.07), mortality (p â€‹= â€‹0.89) or any surgical complication (p â€‹= â€‹0.91). CONCLUSIONS: A LI to surgery after NCRT for LARC increases pCR and TD rates. Local recurrence or survival were not assessed due to unavailable data. We recommend deferring TME until after an interval of 8 weeks following completion of NCRT.

When is neoadjuvant chemotherapy indicated in rectal neuroendocrine tumors? An analysis of the National Cancer Database.

BACKGROUND: Rectal neuroendocrine tumors (rNET) are rare and challenging to manage. While most patients with small rNET can be definitively treated with local excision, the role of chemotherapy in general and neoadjuvant therapy particularly in managing advanced rNET has not been well established. Therefore, this study aimed to determine which patients with rNET may gain a survival benefit from neoadjuvant chemotherapy. METHODS: A retrospective cohort analysis of all patients who underwent surgical resection of rNET in the US National Cancer Database (NCDB) (2004-2019) was performed. First, univariate and multivariate Cox regression analyses were performed to determine the independent predictors of poor overall survival (OS) and define the high-risk groups. Afterward, stratified OS analyses were performed for each high-risk group to assess whether neoadjuvant chemotherapy had a survival benefit in each group. RESULTS: A total of 1837 patients (49.8% female; mean age 56.6 ± 12.3 years) underwent radical resection of a rNET. Tumors > 20 mm in size, clinical T4 tumors, poorly differentiated tumors, and metastatic disease were independent predictors of worse OS and were defined as high-risk groups. Neoadjuvant chemotherapy did not have a significant survival benefit in any of the high-risk groups, except for patients with high-grade rNETs where neoadjuvant therapy significantly improved OS to a mean of 30.9 months compared with 15.9 months when neoadjuvant therapy was not given (p = 0.006). CONCLUSIONS: Neoadjuvant chemotherapy improved the OS of patients with high-grade rNET by 15 months and may be indicated for this group.

Specialty-Certified Colorectal Surgeons Demonstrate Favorable Short-term Surgical Outcomes for Laparoscopic Low Anterior Resection: Assessment of a Japanese Nationwide Database.

BACKGROUND: There are few studies on the impact of a colorectal-specific technically certified surgeon on good surgical outcomes for laparoscopic low anterior resection in the real world. OBJECTIVE: To evaluate the short-term outcomes of laparoscopic low anterior resection with the participation of a certified colorectal surgeon. DESIGN: This was a retrospective cohort study using a Japanese nationwide database. SETTING: This study was conducted as a project for the Japan Society of Endoscopic Surgery and the Japanese Society of Gastroenterological Surgery. PATIENTS: This study included 41,741 patients listed in the National Clinical Database who underwent laparoscopic low anterior resection performed by certified, noncertified, and colorectal-specific certified surgeons, according to the Endoscopic Surgical Skill Qualification System, from 2016 to 2018. MAIN OUTCOME MEASURES: Operative mortality rate and anastomotic leak rate were the primary outcome measures. RESULTS: Overall 30-day mortality and operative mortality were 0.2% and 0.3%, respectively, without significant differences between all kinds of certified and noncertified surgeon groups. Overall anastomotic leak rate was 9.3%, with a significant difference between the 2 groups. Colorectal- and stomach-certified groups had lower 30-day mortality and operative mortality than the biliary-certified and noncertified groups. The anastomotic leak rate was the lowest in the colorectal-certified group. Based on a logistic regression analysis using the risk-adjusted model, operative mortality was significantly higher in the biliary-certified group than in the colorectal-certified group. Moreover, anastomotic leak rate was significantly lower in the colorectal-certified group than in the stomach-certified and noncertified groups. LIMITATIONS: This study was a retrospective study, and there was a possibility of different definitions of anastomotic leak due to the use of a nationwide database. CONCLUSIONS: The participation of a colorectal-specific certified surgeon may decrease the risk of operative mortality and anastomotic leak for laparoscopic low anterior resection. CIRUJANO COLORRECTAL ALTAMENTE CALIFICADO PROVOCA RESULTADOS QUIRRGICOS FAVORABLES A CORTO PLAZO PARA LA RESECCIN ANTERIOR BAJA LAPAROSCPICA EVALUACIN DE LA BASE DE DATOS NACIONAL JAPONESA: ANTECEDENTES:Hay pocos estudios sobre el impacto de un cirujano certificado técnicamente especializado en cáncer colorrectal con un buen resultado quirúrgico para la resección anterior baja laparoscópica en el mundo real.OBJETIVO:Evaluar los resultados a corto plazo de la resección anterior baja laparoscópica con la participación de un cirujano colorrectal certificado.DISEÑO:Este fue un estudio de cohorte retrospectivo que utilizó una base de datos nacional japonesa.AJUSTE:Este estudio se realizó como un proyecto para la Sociedad Japonesa de Cirugía Endoscópica y la Sociedad Japonesa de Cirugía Gastroenterológica.PACIENTES:este estudio incluyó a 41 741 pacientes incluidos en la base de datos clínica nacional que se sometieron a una resección anterior baja laparoscópica realizada por cirujanos certificados, no certificados y certificados específicamente colorrectales, según el Sistema de calificación de habilidades quirúrgicas endoscópicas de 2016 a 2018.PRINCIPALES MEDIDAS DE RESULTADO:La tasa de mortalidad operatoria y la tasa de fuga anastomótica fueron los resultados primarios.RESULTADOS:La mortalidad general a los 30 días y la mortalidad operatoria fueron del 0,2 % y el 0,3 %, respectivamente, sin diferencias significativas entre los grupos de todos los tipos de cirujanos certificados y no certificados. La tasa global de fuga anastomótica fue del 9,3 %, con una diferencia significativa entre los dos grupos. Los grupos con certificación colorrectal y estomacal tuvieron una mortalidad a los 30 días y una mortalidad operatoria más bajas que los grupos con certificación biliar y sin certificación. La tasa de fuga anastomótica fue la más baja en el grupo certificado colorrectal. Con base en un análisis de regresión logística utilizando el modelo ajustado por riesgo, la mortalidad operatoria fue significativamente más alta en el grupo con certificación biliar que en el grupo con certificación colorrectal. Además, la tasa de fuga anastomótica fue significativamente más baja en el grupo con certificación colorrectal que en los grupos con certificación estomacal y sin certificación.LIMITACIONES:Este estudio fue retrospectivo y existía la posibilidad de diferentes definiciones de fuga anastomótica debido al uso de una base de datos nacional.CONCLUSIONES:La participación de un cirujano certificado en video específico colorrectal puede disminuir el riesgo de mortalidad operatoria y fuga anastomótica para la resección anterior baja laparoscópica. (Traducción-Dr. Mauricio Santamaria ).