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

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

A multi-centre randomized controlled trial investigating Consolidation Chemotherapy with and without oxaliplatin in distal rectal cancer and Watch & Wait.

BACKGROUND: Neoadjuvant chemoradiation(nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait-WW). Consolidation chemotherapy(cCT) regimens using fluoropyrimidine-based with or without oxalipatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients. However, the benefit of adding oxaliplatin to cCT compared to fluoropirimidine alone regimens in terms of primary tumor response remains unclear. Since oxalipatin-treatment may be associated with considerable toxicity, it becomes imperative to understand the benefit of its incorporation into standard cCT regimens in terms of primary tumor response. The aim of the present trial is to compare the outcomes of 2 different cCT regimens following nCRT (fluoropyrimidine-alone versus fluoropyrimidine + oxaliplatin) for patients with distal rectal cancer. METHODS: In this multi-centre study, patients with magnetic resonance-defined distal rectal tumors will be randomized on a 1:1 ratio to receive long-course chemoradiation (54 Gy) followed by cCT with fluoropyrimidine alone versus fluoropyrimidine + oxaliplatin. Magnetic resonance(MR) will be analyzed centrally prior to patient inclusion and randomization. mrT2-3N0-1 tumor located no more than 1 cm above the anorectal ring determined by sagittal views on MR will be eligible for the study. Tumor response will be assessed after 12 weeks from radiotherapy(RT) completion. Patients with clinical complete response (clinical, endoscopic and radiological) may be enrolled in an organ-preservation program(WW). The primary endpoint of this trial is decision to organ-preservation surveillance (WW) at 18 weeks from RT completion. Secondary endpoints are 3-year surgery-free survival, TME-free survival, distant metastases-free survival, local regrowth-free survival and colostomy-free survival. DISCUSSION: Long-course nCRT with cCT is associated with improved complete response rates and may be a very attractive alternative to increase the chances for organ-preservation strategies. Fluoropyrimidine-based cCT with or without oxaliplatin has never been investigated in the setting of a randomized trial to compare clinical response rates and the possibility of organ-preservation. The outcomes of this study may significantly impact clinical practice of patients with distal rectal cancer interested in organ-preservation. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT05000697; registered on August 11th, 2021.

Nonoperative Management of Rectal Cancer: The Watch and Wait Strategy.

In recent decades, rectal cancer management has become increasingly challenging for multiple reasons. Proper imaging using dedicated magnetic resonance, standardization of total mesorectal excision, and incorporation of neoadjuvant treatment regimens have contributed to a significant decrease in local recurrence rates. The observation of complete tumor response to radiation or chemoradiation led to the proposal of organ-preservation strategies with avoidance of immediate surgery and close surveillance (Watch and Wait strategy) in selected patients. The purpose of this article is to review the current evidence related to the selection criteria and outcomes in patients enrolled in this Watch and Wait strategy.

Laparoscopic colorectal surgery and discharge within 24 h-who is at risk for readmission?

AIM: The aim was to describe risk factors for hospital readmission in patients undergoing laparoscopic colorectal procedures and being discharged in ≤24 h. METHOD: All consecutive patients undergoing minimally invasive colorectal surgery between 2010 and 2019 from a single institution were retrospectively reviewed. All patients were included in an enhanced recovery programme. Patients who met criteria for hospital discharge were compared according to the need for readmission in a 45-day follow-up. RESULTS: In all, 664 patients underwent minimally invasive colorectal surgery during the study period and 237 (35.7%) were discharged in ≤24 h. Readmission was required in 16 (6.8%) patients discharged in ≤24 h and no postoperative mortality was observed in this group. Patients discharged in ≤24 h were more likely to have benign disease (P < 0.001), fewer associated procedures (P < 0.025) and intracorporeal anastomoses (P < 0.001). The type of surgical procedure (abdominoperineal resection), low rectal tumour, malignant disease, older age and longer operating time were associated with readmission. Age (OR 1.06; P = 0.037), malignant disease (OR 4.39; P = 0.05) and operating time (OR 1.03; P < 0.001) were identified as independent predictive factors for readmission amongst patients being discharged in ≤24 h. CONCLUSION: Highly selected patients undergoing minimally invasive procedures in colorectal surgery may be safely discharged within 24 h following the procedure. High-risk features for readmission include older age, malignant disease and longer operating time.

Nonoperative Management for T2 Low Rectal Cancer: A Western Approach.

The possibility of organ preservation in early rectal cancer has gained popularity during recent years. Patients with early tumor stage and low risk for local recurrence do not usually require neoadjuvant chemoradiation for oncological reasons. However, these patients may be considered for chemoradiation exclusively for the purpose of achieving a complete clinical response and avoid total mesorectal excision. In addition, cT2 tumors may be more likely to develop complete response to neoadjuvant therapy and may constitute ideal candidates for organ-preserving strategies. In the setting where the use of chemoradiation is exclusively used to avoid major surgery, one should consider maximizing tumor response. In this article, we will focus on the rationale, indications, and outcomes of patients with early rectal cancer being treated by neoadjuvant chemoradiation to achieve organ preservation by avoiding total mesorectal excision.

Prediction of Poor Response to Neoadjuvant Chemoradiation in Patients With Rectal Cancer Using a DNA Repair Deregulation Score: Picking the Losers Instead of the Winners.

BACKGROUND: Patients with rectal cancer may undergo neoadjuvant chemoradiation even in early stages in an attempt to achieve complete clinical response and undergo organ preservation. However, prediction of tumor response is unavailable. In this setting, accurate identification of poor responders could spare patients with early stage disease from potentially unnecessary chemoradiation. OBJECTIVE: This study focused on development/test of a score based on DNA repair gene expression to predict response to neoadjuvant chemoradiation in patients with rectal cancer. DESIGN: Pretreatment biopsy samples from patients with rectal cancer undergoing neoadjuvant chemoradiation were collected and underwent gene expression analysis using RNA-Seq (test cohort). A score was constructed using 8 differentially expressed DNA repair genes between good (complete clinical) and poor responders (incomplete clinical) to treatment. The score was validated in 2 independent cohorts of patients undergoing similar treatment strategies and using quantitative polymerase chain reaction and microarray gene expression data. SETTINGS: This was a retrospective analysis of gene expression data from 3 independent institutions. PATIENTS: Patients with rectal cancer undergoing neoadjuvant chemoradiation (50.4-54.0 Gy and 5-fluorouracil-based chemotherapy) were eligible. Patients with complete clinical response, complete pathological response, or ≤10% residual cancer cells were considered good responders. Patients with >10% residual cancer cells were considered poor responders. The test cohort included 25 patients (16 poor responders). Validation cohort 1 included 28 patients (18 poor responders), and validation cohort 2 included 46 patients (22 poor responders). MAIN OUTCOMES MEASURES: Response was correlated with the DNA repair score calculated using the expression levels of 8 DNA repair genes. DNA repair score sensitivity, specificity, and positive and negative predictive values were determined in test and validation cohorts. RESULTS: Poor responders had significantly lower DNA repair scores when compared with good responders across all 3 cohorts, regardless of the gene expression platform used. A low score correctly predicted poor response in 93%, 90%, and 71% in test, validation 1, and validation 2 cohorts. LIMITATIONS: This study was limited by its small sample size, different gene expression platforms, and treatment regimens across different cohorts used. CONCLUSIONS: A DNA repair gene score may predict patients likely to have poor response to chemoradiation. This score may be a relevant tool to be investigated in future studies focused on chemoradiation used in the context of organ preservation. See Video Abstract at http://links.lww.com/DCR/B104. PREDICCIÓN DE RESPUESTA DEFICIENTE A LA RADIO-QUIMIOTERAPIA NEOADYUVANTE EN PACIENTES CON CÁNCER RECTAL UTILIZANDO UNA PUNTUACIÓN DE DESREGULACIÓN DE REPARACIÓN DE ADN: ESCOGER LOS PERDEDORES EN LUGAR DE LOS GANADORES: Los pacientes con cáncer rectal pueden someterse a radio-quimioterapia neoadyuvante incluso en estadios tempranos en el intento por lograr una respuesta clínica completa y permitir una preservación de órgano. Sin embargo, aun no existen herramientas disponible para la prediccion de la respuesta tumoral al tratamiento. En este contexto, la identificación precisa de los tumores con mala respuesta al tratamiento podría evitar que los pacientes con enfermedad en estadio temprano sean sometidos a radio-quimioterapia potencialmente innecesaria.Desarrollo / testeo de una puntuación basada en la expresión genes reparadores del ADN para predecir la respuesta a la nCRT en pacientes con cáncer rectal.Se recogieron muestras de biopsia de pre-tratamiento de pacientes con cáncer rectal sometidos a radio-quimioterapia neoadyuvante y se les realizó un análisis de expresión génica utilizando RNAseq (cohorte de prueba). Se construyó una puntuación utilizando 8 genes de reparación de ADN expresados diferencialmente entre buenos (respuesta clinica completa) y pobres respondedores (respuesta clinica incompleta) al tratamiento. La puntuación se validó en 2 cohortes independientes de pacientes sometidos a estrategias de tratamiento similares y utilizando qPCR y datos de expresión de genes en chips ADN (biotecnología -microarrays).Análisis retrospectivo de los datos de expresión génica de 3 instituciones independientes.Fueron incluidos aquellos pacientes con cáncer rectal sometidos a radio-quimioterapia neoadyuvante (50,4-54 Gy y quimioterapia basada en 5FU). Los pacientes con respuesta clínica completa, respuesta patológica completa o ≤10% de células cancerosas residuales se consideraron buenos respondedores. Los pacientes con> 10% de células cancerosas residuales se consideraron de respuesta deficiente. La cohorte de prueba incluyó a 25 pacientes (16 respondedores pobres). La cohorte de validación n. ° 1 incluyó a 28 pacientes (18 respondedores pobres) y la cohorte de validación n. ° 2 incluyó a 46 pacientes (22 respondedores pobres).La respuesta se correlacionó con la puntuación de reparación de ADN calculada utilizando los niveles de expresión de 8 genes de reparación de ADN. La sensibilidad del puntaje de reparación del ADN, la especificidad, los valores predictivos positivos y negativos se determinaron en las cohortes de prueba y validación.Los malos respondedores tuvieron puntuaciones de reparación de ADN significativamente más bajas en comparación con los buenos respondedores en las 3 cohortes, independientemente de la plataforma de expresión génica utilizada. Una puntuación baja predijo correctamente una respuesta pobre en el 93%, 90% y 71% en las cohortes de prueba, validación n. ° 1 y validación n. ° 2, respectivamente.Pequeño tamaño de la muestra, diferentes plataformas de expresión génica y regímenes de tratamiento en diferentes cohortes utilizadas.La puntuacion basada en genes de reparación del ADN puede predecir los pacientes con respuesta pobre a la radio-quimioterapia. Esta puntuación puede ser una herramienta relevante para investigar en futuros estudios centrados en la radio-quimioterapia utilizada en el contexto de la preservación de órganos. Consulte Video Resumen en http://links.lww.com/DCR/B104. (Traducción-Dr. Xavier Delgadillo and Dr. Laura Melina Fernandez).

Organ Preservation Among Patients With Clinically Node-Positive Rectal Cancer: Is It Really More Dangerous?

BACKGROUND: Select patients with complete clinical response to chemoradiation have been managed without radical surgery. The presence of radiologic evidence of nodal metastases at baseline could be a risk factor for local tumor regrowth, more advanced stage at the time of recurrence, and worse distant metastases-free survival. OBJECTIVE: The purpose of this study was to compare the outcomes of patients with baseline node-positive and node-negative cancer after neoadjuvant chemoradiation and complete clinical response managed nonoperatively. DESIGN: This was a retrospective review of consecutive patients with nonmetastatic distal rectal cancer undergoing neoadjuvant chemoradiation. PATIENTS: Consecutive patients with clinical and radiologic evidence of complete clinical response at 8 to 10 weeks were managed nonoperatively and enrolled in a strict follow-up program (watch and wait). Patients with incomplete clinical response or tumor regrowth after initial complete clinical response were referred to surgery. MAIN OUTCOMES MEASURES: Surgery-free and distant metastases-free survival were compared between patients according to nodal status at baseline. RESULTS: A total of 117 patients with node-positive and 218 with node-negative cancer at baseline were reviewed. Overall, 62 (53.0%; node positive) and 135 (61.9%; node negative) achieved a complete clinical response and were managed nonoperatively (p = 0.13). Patients with baseline node-positive cancer had similar rates of pathologic nodal metastases at the time of recurrence. Five-year surgery-free (39.7% vs 46.8%; p = 0.2) and distant metastases-free survival (77.5% vs 80.5%; p = 0.49) were similar between baseline node-positive and node-negative patients. LIMITATIONS: This was a retrospective study with a small sample size and possible inaccurate nodal staging. CONCLUSIONS: Patients with rectal cancer with node-positive cancer at baseline who develop a complete clinical response after neoadjuvant chemoradiation are not at increased risk for local tumor regrowth or development of more advanced disease at the time of recurrence. These patients seem to be safe candidates for organ-preserving strategies after achieving complete clinical response. See Video Abstract at http://links.lww.com/DCR/A902.

Organ Preservation in cT2N0 Rectal Cancer After Neoadjuvant Chemoradiation Therapy: The Impact of Radiation Therapy Dose-escalation and Consolidation Chemotherapy.

OBJECTIVE: To demonstrate the difference in organ-preservation rates and avoidance of definitive surgery among cT2N0 rectal cancer patients undergoing 2 different chemoradiation (CRT) regimens. BACKGROUND: Patients with cT2N0 rectal cancer are more likely to develop complete response to neoadjuvant CRT. Organ preservation has been considered an alternative treatment strategy for selected patients. Radiation dose-escalation and consolidation chemotherapy have been associated with increased rates of response and may improve chances of organ preservation among these patients. METHODS: Patients with distal and nonmetastatic cT2N0 rectal cancer managed by neoadjuvant CRT were retrospectively reviewed. Patients undergoing standard CRT (50.4 Gy and 2 cycles of 5-FU-based chemotherapy) were compared with those undergoing extended CRT (54 Gy and 6 cycles of 5-FU-based chemotherapy). Patients were assessed for tumor response at 8 to 10 weeks. Patients with complete clinical response (cCR) underwent organ-preservation strategy ("Watch and Wait"). Patients were referred to salvage surgery in the event of local recurrence during follow-up. RESULTS: Thirty-five patients underwent standard and 46 patients extended CRT. Patients undergoing extended CRT were more likely to undergo organ preservation and avoid definitive surgical resection at 5years (67% vs 30%; P = 0.001). After development of a cCR, surgery-free survival is similar between extended and standard CRT groups at 5 years (78% vs 56%; P = 0.12). CONCLUSIONS: Dose-escalation and consolidation chemotherapy leads to increased long-term organ-preservation rates among cT2N0 rectal cancer. After achievement of a cCR, the risk for local recurrence and need for salvage surgery is similar, irrespective of the CRT regimen.

The Estimate of the Impact of Coccyx Resection in Surgical Field Exposure During Abdominal Perineal Resection Using Preoperative High-Resolution Magnetic Resonance.

OBJECTIVE: To estimate the improvement in surgical exposure by removal of the coccyx, during abdomino-perineal resection (APR), in rectal cancer patients. METHODS: Retrospective study of 29 consecutive patients with rectal cancer was carried out. Using MR T2 sagittal series, the solid angle was estimated using the angle determined by the anterior resection margin and the tip of coccyx (no coccyx resection) or the tip of last sacral vertebra (coccyx resection). The solid angle provides an estimate of the tridimensional surface area provided by an original angle resulting in the best estimate of the surgeon's view/exposure to the critical dissecting point of choice (anterior rectal wall). The difference ("Gain") in surgical field exposure by removal of the coccyx was compared by the solid angle variation between the two estimates (with and without the coccyx). RESULTS: Routine removal of the coccyx determines an average 42% (95% CI 27-57%) gain in surgical field exposure area facing the anterior rectal wall at the level of the prostate/vagina by the surgeon. Fifteen (51%) patients had ≥30% (median) estimated gain in surgical field exposure by coccygectomy. There was no association between BMI, age or gender and estimated gain in surgical field exposure area. CONCLUSIONS: Routine removal of the coccyx during APR may result in an average increase in 42% in surgical field exposure during APR's perineal dissection. Precise estimation of surgical field exposure gain by removal of the coccyx may be predicted by MR sagittal series for each individual patient.

Is neoadjuvant chemoradiation with dose-escalation and consolidation chemotherapy sufficient to increase surgery-free and distant metastases-free survival in baseline cT3 rectal cancer?

Patients with cT3 rectal cancer are less likely to develop complete response to neoadjuvant chemoradiation (nCRT) and still face significant risk for systemic relapse. In this setting, radiation (RT) dose-escalation and consolidation chemotherapy in "extended" nCRT regimens have been suggested to improve primary tumor response and decrease the risks of systemic recurrences. For these reasons we compared surgery-free and distant-metastases free survival among cT3 patients undergoing standard or extended nCRT. METHODS: Patients with distal and non-metastatic T3 rectal cancer managed by nCRT were retrospectively reviewed. Patients undergoing standard CRT (50.4 Gy and 2 cycles of 5FU-based chemotherapy) were compared to those undergoing extended CRT (54 Gy and 6 cycles of 5FU-based chemotherapy). Patients were assessed for tumor response at 8-10 weeks. Patients with complete clinical response (cCR) underwent organ-preservation strategy (Watch & Wait). Patients were referred to salvage surgery in the event of local recurrence during follow-up. Cox's logistic regression was performed to identify independent features associated with improved surgery-free survival after cCR and distant-metastases-free survival. RESULTS: 155 patients underwent standard and 66 patients extended CRT. Patients undergoing extended CRT were more likely to harbor larger initial tumor size (p = 0.04), baseline nodal metastases (cN+; p < 0.001) and higher tumor location (p = 0.02). Cox-regression analysis revealed that the type of nCRT regimen was not independently associated with distinct surgery-free survival after cCR or distant-metastases-free survival (p > 0.05). CONCLUSIONS: Dose-escalation and consolidation chemotherapy are insufficient to increase long-term surgery-free survival among cT3 rectal cancer patients and provides no advantage in distant metastases-free survival.

Local Excision and Endoscopic Resections for Early Rectal Cancer.

Radical surgery is considered as the standard treatment for rectal cancer. Transanal local excision has been considered an interesting alternative for the management of selected patients with rectal cancers for many decades. Different approaches had been considered for local excision, from endoscopic submucosal dissection to resections using platforms, such as transanal endoscopic microsurgery or transanal minimally invasive surgery. Identifying the ideal candidate for this approach is crucial, as a local failure after local excision is associated with poor outcomes, even for an initial early rectal tumor. In this article, the diagnostic tools and criteria to select patients for local excision, the different modalities used, and the outcomes are discussed.

Management of the Complete Clinical Response.

Organ preservation is considered in the management of selected patients with rectal cancer. Complete clinical response observed after neoadjuvant chemoradiation for rectal cancer is one of these cases. Patients who present complete clinical response are candidates to the watch-and-wait approach, when radical surgery is not immediately performed and is offered only to patients in the event of a local relapse. These patients are included in a strict follow-up, and up of 70% of them will never be operated during the follow-up. This strategy is associated with similar oncological outcomes as patients operated on, and the advantage of avoiding the morbidity associated to the radical operation. In this article we will discuss in detail the best candidates for this approach, the protocol itself, and the long-term outcomes.

Baseline T Classification Predicts Early Tumor Regrowth After Nonoperative Management in Distal Rectal Cancer After Extended Neoadjuvant Chemoradiation and Initial Complete Clinical Response.

BACKGROUND: Selected patients with rectal cancer and complete clinical response after neoadjuvant chemoradiation have been managed nonoperatively with acceptable outcomes. However, ≈20% of these patients will develop early tumor regrowth. Identification of these patients could select candidates for more intensive follow-up. OBJECTIVE: The purpose of this study was to investigate the influence of baseline radiological T classification on recurrences after a complete clinical response managed nonoperatively after chemoradiation. DESIGN: This was a retrospective review of a prospective collected database. SETTINGS: The study was conducted at a single center. PATIENTS: Patients with distal rectal cancer (cT2-4N0-2M0) undergoing extended chemoradiation (54 Gy + 5-fluorouracil-based chemotherapy) were eligible. Patients were reassessed for tumor response at 10 weeks after radiation completion. Patients with complete clinical response (clinical, radiological, and endoscopic) were managed nonoperatively and strictly followed. MAIN OUTCOMES MEASURES: Complete clinical response rates, early tumor regrowth rates (<12 mo), local recurrence-free survival, and distant metastases-free survival were measured. RESULTS: A total of 91 consecutive patients with rectal cancer underwent extended chemoradiation. Sixty-one patients developed initial complete clinical response (67%). cT2 patients developed similar initial complete clinical response rates compared with cT3/T4 (72% vs 63%; p = 0.403). Early tumor regrowths were more frequent among baseline cT3/4 when compared with cT2 patients (30% vs 3%; p = 0.007). There were no differences in late local recurrences (p = 0.593) or systemic recurrences (p = 0.387). Local recurrence-free survival was significantly better for cT2 patients at 1 year (96% vs 69%; p = 0.009). After Cox regression analysis, baseline T stage was an independent predictor of improved local recurrence-free survival at 1 year (p = 0.03; OR = 0.09 (95% CI, 0.01-0.81)). LIMITATIONS: This study was limited by its small sample size, retrospective nature, and short follow-up. CONCLUSIONS: cT2 patients who develop complete clinical response after extended chemoradiation managed nonoperatively are less likely to develop early tumor regrowths when compared with cT3/4 patients. cT3/4 patients should undergo more intensive follow-up after a complete clinical response to allow for early detection of early regrowths.

New Strategies in Rectal Cancer.

In recent years, our understanding of rectal cancer has improved, including how locally advanced disease responds to chemotherapy and radiation. This has led to new innovations and advances in the treatment of rectal cancer, which includes organ-preserving strategies for responsive disease, and minimally invasive approaces for the performance of total mesorectal excision/protectomyh for persistently advanced disease. This article discusses new strategies for rectal cancer therapy, including Watch and Wait, local excision, minimally invasive proctectomy, and transanal total mesorectal excision particularly in the setting of preoperative multimodality treatment.

Transanal Endoscopic Microsurgery (TEM) Following Neoadjuvant Chemoradiation for Rectal Cancer: Outcomes of Salvage Resection for Local Recurrence.

BACKGROUND: Transanal endoscopic microsurgery (TEM) has been considered an alternative for selected patients with rectal cancer following neoadjuvant chemoradiation (CRT). Immediate total mesorectal completion for all patients with unfavorable pathological features would result in unnecessary protectomies in a significant proportion of patients. Instead, salvage total mesorectal excision (TME) could be restricted for patients developing local recurrence. The aim of the present study is to determine oncological outcomes of salvage resection for local recurrences following CRT and TEM. METHODS: Consecutive patients undergoing TEM following neoadjuvant CRT for rectal cancer were reviewed. Patients with "near" complete response to CRT (≤3 cm; ycT1-2N0) were offered TEM. Salvage surgery was attempted in the event of a local recurrence. RESULTS: A total of 53 patients were managed by CRT followed by TEM. Unfavorable pathological features were present in 36 patients (68 %). None of the patients underwent immediate completion TME. There were 12 patients who developed local recurrence resulting in a 2-year local recurrence-free survival of 77 % (95 % CI, 53-100 %). Of these patients, 9 developed exclusively local recurrences, and all had at least 1 unfavorable pathological feature in the specimen after TEM (100 %). Eight patients (8 of 9) underwent salvage resection (abdominoperineal resection [APR] in 87 %) with CRM+ in 7 of 8 patients (87 %). Four patients developed local re-recurrence after a median 36 months of follow-up. The 2-year local re-recurrence free survival was 60 %. CONCLUSIONS: Salvage resection for local recurrence following CRT and TEM is associated with high rates of R1 resection (CRM+) and local re-recurrence. Immediate completion of TME should be considered for patients with unfavorable pathological features after TEM.

Pitfalls of transanal endoscopic microsurgery for rectal cancer following neoadjuvant chemoradiation therapy.

Transanal endoscopic microsurgery has become a very useful surgical tool for the management of selected cases of rectal cancer. However, the considerably high local recurrence rates led to the introduction of neoadjuvant therapies including radiation with or without chemotherapy. This treatment strategy may result in significant rates of tumor regression allowing the procedure to be offered to a significant proportion of cases. On the other hand, neoadjuvant chemoradiation (CRT) may also determine wound-healing difficulties with significant postoperative pain. In addition, salvage total mesorectal excision in the case of local recurrence may also be a challenging task. Finally, accurate selection criteria for this minimally invasive approach are still lacking and may be influenced by baseline staging, post-treatment staging and final pathology information. Ultimately, selection of patients for this treatment modality remains a significant challenge for the colorectal surgeon who should be aware of the pitfalls of this procedure in the setting of neoadjuvant CRT.

Transanal endoscopic microsurgery for residual rectal cancer (ypT0-2) following neoadjuvant chemoradiation therapy: another word of caution.

BACKGROUND: Significant tumor downstaging among patients with rectal cancer following neoadjuvant chemoradiation has raised the issue of offering patients with small residual cancers restricted to the bowel wall an alternative treatment strategy to total mesorectal excision. Transanal endoscopic microsurgery may allow proper primary tumor resection with promising oncological outcomes, less postoperative morbidity, and minimal long-term sexual, urinary, and fecal continence disorders in comparison with radical resection. OBJECTIVE: The aim of this study was to determine the oncological outcomes of patients with residual rectal cancers restricted to the rectal wall (ypT0-2) following neoadjuvant chemoradiation and transanal endoscopic microsurgery. DESIGN: This study considered a prospective cohort of patients with residual rectal cancers following neoadjuvant chemoradiation treated by transanal endoscopic microsurgery and no additional systemic therapy. SETTINGS: This study was a single-institution experience. PATIENTS: Patients with adenocarcinoma of the rectum located no more than 7 cm from the anal verge and endorectal ultrasound- or magnetic resonance-staged cT2-4N0-2M0 treated by neoadjuvant chemoradiation (50.4-54 Gy and 5-fluorouracil-based chemotherapy) were eligible for the study. Patients with small residual tumors (≤3 cm) radiologically staged ycT0-2N0 were treated by transanal endoscopic microsurgery. INTERVENTIONS: Transanal endoscopic microsurgery was performed. MAIN OUTCOME MEASURES: The primary outcome measured was local recurrence. RESULTS: Of the 27 patients treated by transanal endoscopic microsurgery, 3 had ypT0, 6 had ypT1, and 18 had ypT2 cancers. All patients underwent R0 transanal endoscopic microsurgery excision. Local recurrence was observed in 4 (15%) patients after a median follow-up of 15 months. Only lymphovascular invasion was an independent predictive factor for local failure (p = 0.04). Tumor size, ypT status, T-status downstaging, lateral/radial margins, and tumor regression grade were not predictors of local failure. LIMITATIONS: This study was limited by the small sample size and limited follow-up. CONCLUSIONS: A local failure rate of 15% after transanal endoscopic microsurgery for patients with residual rectal cancers restricted to the bowel wall (ypT0-2) may limit the indication of this procedure to highly selected patients as an alternative to standard radical total mesorectal excision.