Short-course radiation with consolidation chemotherapy does not increase operative morbidity compared to long-course chemoradiation: A retrospective study of the US rectal cancer consortium.

BACKGROUND AND OBJECTIVES: Neoadjuvant short-course radiation and consolidation chemotherapy (SC TNT) remains less widely used for rectal cancer in the United States than long-course chemoradiation (LCRT). SC TNT may improve compliance and downstaging; however, a longer radiation-to-surgery interval may worsen pelvic fibrosis and morbidity with total mesorectal excision (TME). A single, US-center retrospective analysis has shown comparable risk of morbidity after neoadjuvant short-course radiation with consolidation chemotherapy (SC TNT) and long-course chemoradiation (LCRT). Validation by a multi-institutional study is needed. METHODS: The US Rectal Cancer Consortium database (2010-2018) was retrospectively reviewed for patients with nonmetastatic, rectal adenocarcinoma treated with neoadjuvant LCRT or SC TNT before TME. The primary endpoint was severe postoperative morbidity. Cohorts were compared by univariate analysis. Multivariable logistic regression modeled the odds of severe complication. RESULTS: Of 788 included patients, 151 (19%) received SC TNT and 637 (81%) LCRT. The SC TNT group had fewer distal tumors (33.8% vs. 50.2%, p < 0.0001) and more clinical node-positive disease (74.2% vs. 47.6%, p < 0.0001). The intraoperative complication rate was similar (SC TNT 5.3% vs. 4.4%, p = 0.65). There was no difference in overall postoperative morbidity (38.4% vs. 46.3%, p = 0.08). Severe morbidity was similar with low anterior resection (9.1% vs. 15.3%, p = 0.10) and abdominoperineal resection (24.4% vs. 29.7%, p = 0.49). SC TNT did not increase the odds of severe morbidity relative to LCRT on multivariable analysis (OR 0.64, 95% CI 0.37-1.10). CONCLUSIONS: SC TNT does not increase morbidity after TME for rectal cancer relative to LCRT. Concern for surgical complications should not discourage the use of SC TNT when aiming to increase the likelihood of complete clinical response.

Short-Course TNT Improves Rectal Tumor Downstaging in a Retrospective Study of the US Rectal Cancer Consortium.

BACKGROUND AND OBJECTIVES: The RAPIDO trial showed promising rates of pathologic complete response (pCR) after neoadjuvant short-course radiation with consolidation chemotherapy (total neoadjuvant therapy [SC TNT]) for rectal cancer. Only single-center reviews comparing tumor downstaging between SC TNT and long-course chemoradiation (LCRT) have been published in the United States. We reviewed our multi-institutional experience with both. METHODS: The US Rectal Cancer Consortium database (2007-2018) including data from six high-volume rectal cancer care centers was reviewed. Patients with nonmetastatic, rectal adenocarcinoma who had neoadjuvant LCRT alone or SC TNT before excision or definitive nonoperative management were included. The primary outcome was the rate of complete response (CR), including pCR or durable (12 month) clinical complete response. RESULTS: Of 857 included patients, 175 (20%) received SC TNT and 682 (80%) received LCRT. The LCRT group had more low tumors (51.8% vs. 37.1%, p < 0.0001) and more clinically node-negative disease (31.8% vs. 22.3%, p < 0.0001). The CR rate was higher after SC TNT (34.1% vs. 20.3%, p = 0.0001). SC TNT was a predictor of CR (OR: 2.52, CI: 1.68-3.78). SC TNT patients completing 5-6 months of consolidation chemotherapy had a CR rate of 42.9%. There was no difference in 3-year PFS. CONCLUSIONS: SC TNT increases CR rate when compared to LCRT. For patients seeking nonoperative options or fewer radiation treatments, SC TRT should be preferred over LCRT alone.

Radiotherapy for Rectal Cancer: How Much is Enough?

Though resection has been the mainstay of treatment for nonmetastatic rectal cancer over the past century, radiation has become an increasingly integral component of care for locally advanced disease. Today, two predominant radiotherapy approaches-hyperfractionated chemoradiotherapy and "short-course" radiation-are widely utilized to reduce local recurrence and, in some cases, cure disease. Both have been incorporated into total neoadjuvant therapy (TNT) regimens and achieved excellent local control and superior complete response rates compared to chemoradiation alone. Additionally, initial results of "watch and wait" protocols utilizing either radiation modality have been promising. Yet, differences do exist; though short course is cheaper and more convenient for patients, recently published data may show superior complete response and local recurrence rates with chemoradiation. Ultimately, direct comparisons of short-course radiotherapy against chemoradiation within the TNT framework are needed to identify optimal radiation regimens in the treatment of locally advanced rectal cancer.

Discharge Prescribing Protocol Decreases Opioids in Circulation and Does Not Increase Refills After Colorectal Surgery.

BACKGROUND: Up to 10% of patients develop new, persistent opioid use after surgery. We aimed to assess our prescribing practices and patient utilization of opioids after colorectal surgery. OBJECTIVE: This study aimed to implement an opioid-prescribing protocol that will minimize the number of postoperative opioids to decrease community circulation and persistent use by patients. DESIGN: This was a single-institution, prospective study based on questionnaires of postoperative patients in 2019 and 2020 to determine opioid prescribing and usage patterns. Based on these preliminary results, a protocol was implemented in which patients were discharged with 5 or 15 oxycodone 5 mg equivalents based on opioid usage in the 24 hours before discharge. Patients were surveyed after protocol implementation. SETTINGS: Our institution is a large referral center for surgical treatment of colorectal disease. PATIENTS: Adults who underwent inpatient abdominal colorectal procedures. MAIN OUTCOME MEASURES: End points included the number of opioids prescribed, number of prescribed opioids taken, and refill rate. Nonparametric testing was used. RESULTS: Of 77 eligible patients, 61 were opioid naive. Preprotocol, opioid-naive patients (n = 29) were prescribed a median of 30 (interquartile range [IQR], 30-45) tablets but took only 10 (IQR, 0-10; p < 0.0001). Eighty-three percent took 20 or fewer tablets. After protocol implementation, opioid-naive patients (n = 32) were prescribed fewer tablets (median 15; IQR, 7-15; p < 0.0001) but took a similar number of tablets as the preprotocol group (median 10; IQR, 0-10; p = 0.21). The refill rate remained similar (13.8% vs 18.8%; p = 0.60). Protocol adherence was 90.6%. LIMITATIONS: This study is limited by sample size, cohort heterogeneity, and generalizability. CONCLUSIONS: Patients took significantly fewer opioids than were prescribed. Our protocol limited overprescribing and resulted in fewer opioids in the community without opportunity costs such as increased refills. Long-term studies are needed to assess the effects of persistent opioid use after surgery. See Video Abstract at http://links.lww.com/DCR/C93 .

ANTECEDENTES: Hasta el 10% de los pacientes desarrollan un nuevo uso persistente de opioides después de la cirugía. Nuestro objetivo fue evaluar nuestras prácticas de prescripción y la utilización de opioides por parte de los pacientes después de la cirugía colorrectal. OBJETIVO: Nuestro objetivo es implementar un protocolo de prescripción de opioides que minimice la cantidad de opioides posoperatorios para disminuir la circulación en la comunidad y el uso persistente por parte de los pacientes. DISEÑO: Estudio prospectivo, de una sola institución, basado en cuestionarios de pacientes postoperatorios en 2019 y 2020 para determinar los patrones de prescripción y uso de opioides. Con base en estos resultados preliminares, se implementó un protocolo en el que los pacientes eran dados de alta con 5 o 15 equivalentes de oxicodona de 5 mg según el uso de opioides en las 24 horas previas al alta. Los pacientes fueron encuestados después de la implementación del protocolo. AJUSTES: Nuestra institución es un gran centro de referencia para el tratamiento quirúrgico de la enfermedad colorrectal. PACIENTES: Adultos que se sometieron a procedimientos colorrectales abdominales con hospitalización. PRINCIPALES MEDIDAS DE RESULTADO: Los criterios de valoración incluyeron el número de opioides recetados, el número de opioides recetados tomados y la tasa de reabastecimiento. Se utilizaron pruebas no paramétricas. RESULTADOS: De 77 pacientes elegibles, 61 no habian recibido opioides. A los pacientes sin tratamiento previo con opioides antes del protocolo (n = 29) se les prescribió una mediana de 30 (rango intercuartilico [RIC] 30­45) comprimidos, pero solo tomaron 10 (RIC 0.10, p < 0,0001). El ochenta y tres por ciento tomo ≤20 comprimidos. Despues de la implementacion del protocolo, a los pacientes sin tratamiento previo con opioides (n = 32) se les prescribieron menos comprimidos (15; RIC 7.15, p < 0,0001), pero tomaron un numero similar antes de la intervención (10; RIC 0­10, p = 0,21). La tasa de reabastecimiento se mantuvo similar (13,8% frente a 18,8%, p = 0,60). La adherencia al protocolo fue del 90,6%. LIMITACIONES: Este estudio está limitado por el tamaño de la muestra, la heterogeneidad de la cohorte y la generalización. CONCLUSIONES: Los pacientes tomaron significativamente menos opioides de los prescritos. Nuestro protocolo limitó la prescripción excesiva y dio como resultados menos opioides en la comunidad sin costos de oportunidad, como el aumento de reabastecimiento. Se necesitan estudios a largo plazo para evaluar los efectos sobre el uso persistente de opioides después de la cirugía. Consulte Video Resumen en http://links.lww.com/DCR/C93 . (Traducción­Dr. Francisco M. Abarca-Rendon).

Circumferential Resection Margin as Predictor of Nonclinical Complete Response in Nonoperative Management of Rectal Cancer.

BACKGROUND: Short-course radiation therapy and consolidation chemotherapy with nonoperative intent has emerged as a novel treatment paradigm for patients with rectal cancer, but there are no data on the predictors of clinical complete response. OBJECTIVE: Evaluate the predictors of clinical complete response and survival. DESIGN: Retrospective cohort. SETTINGS: National Cancer Institute-designated cancer center. PATIENTS: Patients with stage I to III rectal adenocarcinoma treated between January 2018 and May 2019 (n = 86). INTERVENTIONS: Short-course radiation therapy followed by consolidation chemotherapy. MAIN OUTCOME MEASURES: Logistic regression was performed to assess for predictors of clinical complete response. The end points included local regrowth-free survival, regional control, distant metastasis-free survival, and overall survival. RESULTS: A positive (+) circumferential resection margin by MRI at diagnosis was a significant predictor of nonclinical complete response (OR: 4.1, p = 0.009) when adjusting for CEA level and primary tumor size. Compared to patients with a negative (-) pathologic circumferential resection margin, patients with a positive (+) pathologic circumferential resection margin had inferior local regrowth-free survival (29% vs 87%, p < 0.001), regional control (57% vs 94%, p < 0.001), distant metastasis-free survival (43% vs 95%, p < 0.001), and overall survival (86% vs 95%, p < 0.001) at 2 years. However, the (+) and (-) circumferential resection margin by MRI subgroups in patients who had a clinical complete response both had similar regional control, distant metastasis-free survival, and overall survival of more than 90% at 2 years. LIMITATIONS: Retrospective design, modest sample size, short follow-up, and the heterogeneity of treatments. CONCLUSIONS: Circumferential resection margin involvement by MRI at diagnosis is a strong predictor of nonclinical complete response. However, patients who achieve a clinical complete response after short-course radiation therapy and consolidation chemotherapy with nonoperative intent have excellent clinical outcomes regardless of the initial circumferential resection margin status. See Video Abstract at http://links.lww.com/DCR/C190 . EL MARGEN DE RESECCIN CIRCUNFERENCIAL COMO PREDICTOR NO CLNICO DE RESPUESTA COMPLETA EN EL MANEJO CONSERVADOR DEL CNCER DE RECTO: ANTECEDENTES:La radioterapia de corta duración y la quimioterapia de consolidación en el manejo conservador, han surgido como un nuevo paradigma de tratamiento, para los pacientes con cáncer de recto, lastimosamente no hay datos definitivos sobre los predictores de una respuesta clínica completa.OBJETIVO:Evaluar los predictores de respuesta clínica completa y de la sobrevida.DISEÑO:Estudio retrospectivo de cohortes.AJUSTES:Centro oncológico designado por el NCI.PACIENTES:Adenocarcinomas de recto estadio I-III tratados entre 01/2018 y 05/2019 (n = 86).INTERVENCIONES:Radioterapia de corta duración seguida de quimioterapia de consolidación.PRINCIPALES MEDIDAS DE RESULTADO:Se realizó una regresión logística para evaluar los predictores de respuesta clínica completa. Los criterios de valoración incluyeron la sobrevida libre de recidiva local, el control regional, la sobrevida libre de metástasis a distancia y la sobrevida general.RESULTADOS:Un margen de resección circunferencial positivo (+) evaluado por imagenes de resonancia magnética nuclear en el momento del diagnóstico fue un predictor no clínico muy significativo de respuesta completa (razón de probabilidades/ OR: 4,1, p = 0,009) al ajustar el nivel de antígeno carcinoembrionario y el tamaño del tumor primario. Comparando con los pacientes que presetaban un margen de resección circunferencial patológico negativo (-), los pacientes con un margen de resección circunferencial patológico positivo (+) tuvieron una sobrevida libre de recidiva local (29% frente a 87%, p < 0,001), un control regional (57% frente a 94%, p < 0,001), una sobrevida libre de metástasis a distancia (43% frente a 95%, p < 0,001) y una sobrevida global (86% frente a 95%, p < 0,001) inferior en 2 años de seguimiento. Sin embargo, los subgrupos de margen de resección circunferencial (+) y (-) evaluados por imágenes de resonancia magnética nuclear en pacientes que tuvieron una respuesta clínica completa tuvieron un control regional similar, una sobrevida libre de metástasis a distancia y una sobrevida general >90% en 2 años de seguimiento.LIMITACIONES:Diseño retrospectivo, tamaño modesto de la muestra, seguimiento corto y heterogeneidad de tratamientos.CONCLUSIONES:La afectación del margen de resección circunferencial evaluado por resonancia magnética nuclear al momento del diagnóstico es un fuerte factor predictivo no clínico de respuesta completa. Sin embargo, los pacientes que logran una respuesta clínica completa después de un curso corto de radioterapia y quimioterapia de consolidación como manejo conservador tienen excelentes resultados clínicos independientemente del estado del margen de resección circunferencial inicial. Consulte Video Resumen en http://links.lww.com/DCR/C190 . (Traducción-Dr. Xavier Delgadillo ).

Perioperative Complications After Proctectomy for Rectal Cancer: Does Neoadjuvant Regimen Matter?

OBJECTIVE: Investigate the association between neoadjuvant treatment strategy and perioperative complications in patients undergoing proctectomy for nonmetastatic rectal cancer. SUMMARY OF BACKGROUND DATA: Neoadjuvant SC-TNT is an alternative to neoadjuvant CRT for rectal cancer. Some have argued that short-course radiation and extended radiation-to-surgery intervals increase operative difficulty and complication risk. However, the association between SC-TNT and surgical complications has not been previously investigated. METHODS: This single-center retrospective cohort study included patients undergoing total mesorectal excision for nonmetastatic rectal cancer after SC-TNT or CRT between 2010 and 2018. Univariate analysis of severe POM and multiple secondary outcomes, including overall POM, intraoperative complications, and resection margins, was performed. Logistic regression of severe POM was also performed. RESULTS: Of 415 included patients, 156 (38%) received SC-TNT and 259 (62%) received CRT. The cohorts were largely similar, though patients with higher tumors (69.9% vs 47.5%, P < 0.0001) or node-positive disease (76.9% vs 62.6%, P = 0.004) were more likely to receive SC-TNT. We found no difference in incidence of severe POM (9.6% SC-TNT vs 12.0% CRT, P = 0.46) or overall POM (39.7% SC-TNT vs 37.5% CRT, P = 0.64) between cohorts. Neoadjuvant regimen was also not associated with a difference in severe POM (odds ratio 0.42, 95% confidence interval 0.04-4.70, P = 0.48) in multivariate analysis. There was no significant association between neoadjuvant regimen and any secondary outcome. CONCLUSION: In rectal cancer patients treated with SC-TNT and proctectomy, we found no significant association with POM compared to patients undergoing CRT. SC-TNT does not significantly increase the risk of POM compared to CRT.

Total Neoadjuvant Therapy With Short-Course Radiation: US Experience of a Neoadjuvant Rectal Cancer Therapy.

BACKGROUND: Short-course radiation followed by chemotherapy as total neoadjuvant therapy has been investigated primarily in Europe and Australia with increasing global acceptance. There are limited data on this regimen's use in the United States, however, potentially delaying implementation. OBJECTIVE: This study aimed to compare clinical performance and oncologic outcomes of 2 rectal cancer neoadjuvant treatment modalities: short-course total neoadjuvant therapy versus standard chemoradiation. DESIGN: This is a retrospective cohort study. SETTING: This study was performed at a National Cancer Institute-designated cancer center. PATIENTS: A total of 413 patients had locally advanced rectal cancers diagnosed from June 2009 to May 2018 and received either short-course total neoadjuvant therapy or standard chemoradiation. INTERVENTIONS: There were 187 patients treated with short-course total neoadjuvant therapy (5 × 5 Gy radiation followed by consolidation oxaliplatin-based chemotherapy) compared with 226 chemoradiation recipients (approximately 50.4 Gy radiation in 28 fractions with concurrent fluorouracil equivalent). MAIN OUTCOME MEASURES: Primary end points were tumor downstaging, measured by complete response and "low" neoadjuvant rectal score rates, and progression-free survival. Secondary analyses included treatment characteristics and completion, sphincter preservation, and recurrence rates. RESULTS: Short-course total neoadjuvant therapy was associated with higher rates of complete response (26.2% vs 17.3%; p = 0.03) and "low" neoadjuvant rectal scores (40.1% vs 25.7%; p < 0.01) despite a higher burden of node-positive disease (78.6% vs 68.9%; p = 0.03). Short-course recipients also completed trimodal treatment more frequently (88.4% vs 50.4%; p < 0.01) and had fewer months with temporary stomas (4.8 vs 7.0; p < 0.01). Both regimens achieved comparable local control (local recurrence: 2.7% short-course total neoadjuvant therapy vs 2.2% chemoradiation, p = 0.76) and 2-year progression-free survival (88.2% short-course total neoadjuvant therapy (95% CI, 82.9-93.5) vs 85.6% chemoradiation (95% CI, 80.5-90.7)). LIMITATIONS: Retrospective design, unbalanced disease severity, and variable dosing of neoadjuvant consolidation chemotherapy were limitations of this study. CONCLUSIONS: Short-course total neoadjuvant therapy was associated with improved downstaging and similar progression-free survival compared with chemoradiation. These results were achieved with shortened radiation courses, improved treatment completion, and less time with diverting ostomies. Short-course total neoadjuvant therapy is an optimal regimen for locally advanced rectal cancer. See Video Abstract at http://links.lww.com/DCR/B724.TERAPIA NEOADYUVANTE TOTAL CON RADIACIÓN DE CORTA DURACIÓN: EXPERIENCIA ESTADOUNIDENSE DE UNA TERAPIA NEOADYUVANTE CONTRA EL CÁNCER DE RECTO. ANTECEDENTES: La radiación de corta duración seguida de quimioterapia como terapia neoadyuvante total se ha investigado principalmente en Europa y Australia con una aceptación mundial cada vez mayor. Sin embargo, datos limitados sobre el uso de este régimen en los Estados Unidos, han potencialmente retrasando su implementación. OBJETIVO: Comparar el desempeño clínico y los resultados oncológicos de dos modalidades de tratamiento neoadyuvante del cáncer de recto: terapia neoadyuvante total de corta duración versus quimioradiación. estándar. DISEO: Cohorte retrospectivo. AJUSTE: Centro oncológico designado por el NCI. PACIENTES: Un total de 413 cánceres rectales localmente avanzados diagnosticados entre junio de 2009 y mayo de 2018 que recibieron cualquiera de los regímenes neoadyuvantes. INTERVENCIONES: Hubo 187 pacientes tratados con terapia neoadyuvante total de ciclo corto (radiación 5 × 5 Gy seguida de quimioterapia de consolidación basada en oxaliplatino) en comparación con 226 pacientes de quimiorradiación (aproximadamente 50,4 Gy de radiación en 28 fracciones con equivalente de fluorouracilo concurrente). PRINCIPALES MEDIDAS DE RESULTADO: Los criterios primarios de valoración fueron la disminución del estadio del tumor, medido por la respuesta completa y las tasas de puntuación rectal neoadyuvante "baja", y la supervivencia libre de progresión. Los análisis secundarios incluyeron las características del tratamiento y las tasas de finalización, conservación del esfínter y recurrencia. RESULTADOS: La terapia neoadyuvante total de corta duración, se asoció con tasas más altas de respuesta completa (26,2% versus 17,3%, p = 0,03) y puntuaciones rectales neoadyuvantes "bajas" (40,1% versus 25,7%, p < 0,01) a pesar de una mayor carga de enfermedad con ganglios positivos (78,6% versus 68,9%, p = 0,03). Los pacientes de ciclo corto también completaron el tratamiento trimodal con mayor frecuencia (88,4% versus 50,4%, p < 0,01) y tuvieron menos meses con estomas temporales (4,8 versus 7,0, p < 0,01). Ambos regímenes lograron un control local comparable (recidiva local: 2,7% de SC-TNT versus 2,2% de TRC, p = 0,76) y supervivencia libre de progresión a 2 años (88,2% de SC-TNT [IC: 82,9 - 93,5] versus 85,6% CRT [CI: 80,5 - 90,7]). LIMITACIONES: Diseño retrospectivo, gravedad de la enfermedad desequilibrada y dosificación variable de quimioterapia neoadyuvante de consolidación. CONCLUSIONES: La terapia neoadyuvante total de ciclo corto se asoció con una mejora en la reducción del estadio y una supervivencia libre de progresión similar en comparación con la quimioradiación. Estos resultados se lograron con ciclos de radiación más cortos, tratamientos mejor finalizados y menos tiempo en ostomías de derivación. La terapia neoadyuvante total de corta duración es un régimen óptimo para el cáncer de recto localmente avanzado. Consulte Video Resumen en http://links.lww.com/DCR/B724. (Traducción- Dr. Fidel Ruiz Healy).

Thoracic Epidural Analgesia: Does It Enhance Recovery?

BACKGROUND: Thoracic epidural analgesia has been shown to be an effective method of pain control. The utility of epidural analgesia as part of an enhanced recovery after surgery protocol is debatable. OBJECTIVE: This study aimed to determine if the use of thoracic epidural analgesia in an enhanced recovery after surgery protocol decreases hospital length of stay or inpatient opioid consumption after elective colorectal resection. DESIGN: This is a single-institution retrospective cohort study. SETTINGS: The study was performed at a high-volume, tertiary care center in the Midwest. An institutional database was used to identify patients. PATIENTS: All patients undergoing elective transabdominal colon or rectal resection by board-certified colon and rectal surgeons from 2013 to 2017 were included. MAIN OUTCOME MEASURES: The main outcome was length of stay. The secondary outcome was oral morphine milligram equivalents consumed during the first 48 hours. RESULTS: There were 1006 patients (n = 815 epidural, 191 no epidural) included. All patients received multimodal analgesia with opioid-sparing agents. Univariate analysis demonstrated no difference in length of stay between those who received thoracic epidural analgesia and those who did not (median, 4 vs 5 days; p = 0.16), which was substantiated by multivariable linear regression. Subgroup analysis showed that the addition of epidural analgesia resulted in no difference in length of stay regardless of an open (n = 362; p = 0.66) or minimally invasive (n = 644; p = 0.46) approach. Opioid consumption data were available after 2015 (n = 497 patients). Univariate analysis demonstrated no difference in morphine milligram equivalents consumed in the first 48 hours between patients who received epidural analgesia and those who did not (median, 135 vs 110 oral morphine milligram equivalents; p = 0.35). This was also confirmed by multivariable linear regression. LIMITATIONS: The retrospective observational design was a limitation of this study. CONCLUSION: The use of thoracic epidural analgesia within an enhanced recovery after surgery protocol was not found to be associated with a reduction in length of stay or morphine milligram equivalents consumed within the first 48 hours. We cannot recommend routine use of thoracic epidural analgesia within enhanced recovery after surgery protocols. See Video Abstract at http://links.lww.com/DCR/A765.

Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial.

BACKGROUND: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response. OBJECTIVE: The purpose of this study was to analyze disease-free and overall survival. DESIGN: This was a nonrandomized phase II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS: Four sequential study groups with stage II or III rectal cancer were included. INTERVENTION: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6. MAIN OUTCOME MEASURES: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study. RESULTS: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03). LIMITATIONS: The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients. CONCLUSIONS: Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.

Benchmarking rectal cancer care: institutional compliance with a longitudinal checklist.

BACKGROUND: In 2012, the American Society of Colon and Rectal Surgeons published the Rectal Cancer Surgery Checklist, a consensus document listing 25 essential elements of care for all patients undergoing radical surgery for rectal cancer. The authors herein examine checklist adherence in a mature, multisurgeon specialty academic practice. MATERIALS AND METHODS: A retrospective medical record review of patients undergoing elective radical resection for rectal adenocarcinoma over a 23-mo period was conducted. Checklists were completed post hoc for each patient, and these results were tabulated to determine levels of compliance. Subgroup analyses by compliance and experience levels of the treating surgeon were performed. RESULTS: A total of 161 patients underwent resection, demonstrating a median completion rate of 84% per patient. Poor compliance was noted consistently in documenting baseline sexual function (0%), multidisciplinary discussion of treatment plans (16.8%), pelvic nerve identification (8.7%) and leak testing (52.9%), and radial margin status reporting (57.5%). Junior surgeons achieved higher rates of compliance and were more likely to restage after neoadjuvant therapy (67.9% versus 29.4%, P < 0.001), discuss patients at tumor board (31.3% versus 13.2%, P = 0.014), and document leak testing (86.7% versus 47.2%, P = 0.005) compared with senior surgeons. CONCLUSIONS: Checklist compliance within a high-volume, specialty academic practice remains varied. Only surgeon experience level was significantly associated with high checklist compliance. Junior surgeons achieved greater compliance with certain items, particularly those that reinforce decision-making. Further efforts to standardize rectal cancer care should focus on checklist implementation, targeted surgeon outreach, and assessment of checklist compliance correlation to clinical outcomes.

Combined rectopexy and sacrocolpopexy is safe for correction of pelvic organ prolapse.

PURPOSE: Pelvic floor abnormalities often affect multiple organs. The incidence of concomitant uterine/vaginal prolapse with rectal prolapse is at least 38%. For these patients, addition of sacrocolpopexy to rectopexy may be appropriate. Our aim was to determine if addition of sacrocolpopexy to rectopexy increases the procedural morbidity over rectopexy alone. METHODS: We utilized the ACS-NSQIP database to examine female patients who underwent rectopexy from 2005 to 2014. We compared patients who had a combined procedure (sacrocolpopexy and rectopexy) to those who had rectopexy alone. Thirty-day morbidity was compared and a multivariable model constructed to determine predictors of complications. RESULTS: Three thousand six hundred patients underwent rectopexy; 3394 had rectopexy alone while 206 underwent a combined procedure with the addition of sacrocolpopexy. Use of the combined procedure increased significantly from 2.6 to 7.7%. Overall morbidity did not differ between groups (14.8% rectopexy alone vs. 13.6% combined procedure, p = 0.65). Significant predictors of morbidity included addition of resection to a rectopexy procedure, elevated BMI, smoking, wound class, and ASA class. After controlling for these and other patient factors, the addition of sacrocolpopexy to rectopexy did not increase overall morbidity (OR 1.00, p = 0.98). CONCLUSIONS: There is no difference in operative morbidity when adding sacrocolpopexy to a rectopexy procedure. Despite a modest increase in utilization of combined procedures over time, the overall rate remains low. These findings support the practice of multidisciplinary evaluation of patients presenting with rectal prolapse, with the goal of offering concurrent surgical correction for all compartments affected by pelvic organ prolapse disorders.

Preoperative Chemotherapy and Survival for Large Anorectal Gastrointestinal Stromal Tumors: A National Analysis of 333 Cases.

PURPOSE: Anorectal gastrointestinal stromal tumors (GISTs) are exceedingly rare, and management remains controversial in regard to local resection (LR) and preoperative chemotherapy. METHODS: The National Cancer Data Base was queried from 1998 to 2012 for cases of GIST resection in the rectum or anus. Patient demographics, type of surgery (LR vs. radical excision [RE]), short-term outcomes, and overall survival (OS) were analyzed. Preoperative chemotherapy was recorded following the US FDA approval of imatinib in 2002. RESULTS: Overall, 333 patients with resection of anorectal GISTs were included. Mean age at presentation was 62.3 years (range 22-90), and median tumor size was 4.0 cm (interquartile range 2.2-7.0). Five-year OS for all patients was 77.6%. In a multivariable survival analysis, only age and tumor size >5 cm (hazard ratio 2.48, 95% confidence interval 1.50-4.01; p = 0.004) were associated with increased mortality. One hundred and sixty-three (49.0%) patients underwent LR, compared with 158 (47.4%) who underwent RE. For tumors smaller than 5 cm, no difference in 5-year survival by surgical approach was observed (LR 82.3% vs. RE 82.6%; p = 0.71). Fifty-nine patients (17.7%) received preoperative chemotherapy; for patients undergoing RE with tumors >5 cm, there was decreased mortality in the group who received preoperative chemotherapy (5-year OS with chemotherapy 79.2% vs. no chemotherapy 51.2%; p = 0.03). CONCLUSIONS: Size is the most important determinant in survival following resection. Local excision is common, with resection split between LR and RE. For smaller tumors, LR may be adequate therapy. Preoperative chemotherapy may result in improved survival for large tumors treated with radical resection, but the data are imperfect.

Omission of Adjuvant Chemotherapy Is Associated With Increased Mortality in Patients With T3N0 Colon Cancer With Inadequate Lymph Node Harvest.

BACKGROUND: Adjuvant chemotherapy for T3N0 colon cancer is controversial. National guidelines recommend its use in patients with stage II with high-risk features, including lymph node harvest of less than 12, yet this treatment is underused. OBJECTIVE: The purpose of this study was to demonstrate that the use of adjuvant chemotherapy in patients with T3N0 adenocarcinoma with inadequate lymph node harvest is beneficial. DESIGN: This was a retrospective population-based study of patients with resected T3N0 adenocarcinoma of the colon. SETTINGS: The National Cancer Database was queried from 2003 to 2012. PATIENTS: A total of 134,567 patients with T3N0 colon cancer were included in this analysis. MAIN OUTCOME MEASURES: The use of chemotherapy, short-term outcomes, and overall survival was evaluated. Clinicopathologic factors associated with omission of chemotherapy were also analyzed. RESULTS: Inadequate lymph node harvest was observed in 23.3% of patients, and this rate decreased over the study period from 46.8% in 2003 to 12.5% in 2012 (p < 0.0001). Overall 5-year survival for patients with T3N0 cancer was 66.8%. Inadequate lymph node harvest among these patients was associated with lower overall 5-year survival (58.7% vs 69.8%; p < 0.001). The use of adjuvant chemotherapy among patients with T3N0 cancer after inadequate lymph node harvest was only 16.7%. In a multivariable analysis, factors associated with failure to receive chemotherapy included advanced age (OR = 0.44 (95% CI, 0.43-0.45)), increased comorbidities (OR = 0.7 (95% CI, 0.66-0.76)), and postoperative readmission (OR = 0.78 (95% CI, 0.67-0.91)). Patients with inadequate lymph node harvest who received adjuvant chemotherapy had improved 5-year survival (chemotherapy, 78.4% vs no chemotherapy, 54.7%; p < 0.001). Even when controlling for all of the significant variables, the administration of chemotherapy remained a predictor of decreased mortality (HR = 0.57 (95% CI, 0.54-0.60); p < 0.001). LIMITATIONS: This study was limited by its retrospective, population-based design. CONCLUSIONS: Patients with T3N0 colon cancer with inadequate lymph node harvest who receive adjuvant chemotherapy have increased overall survival. Despite this survival benefit, a fraction of these patients receive adjuvant chemotherapy. Barriers to chemotherapy are multifactorial.

Impaired outcome colitis-associated rectal cancer versus sporadic cancer.

BACKGROUND: The surgical management of colitis-associated rectal cancer (CARC) is not well defined. This study determines outcomes after surgery for CARC compared with sporadic rectal cancer. MATERIALS AND METHODS: This is a retrospective cohort study comparing 27 patients with CARC with 54 matched patients with sporadic cancer. Matching criteria included age, gender, neoadjuvant chemoradiation, and American Joint Committee on Cancer stage. Outcome measures were disease-free and overall survival, tumor characteristics, and postoperative morbidity. RESULTS: Compared to those with sporadic rectal cancer, patients with CARC underwent proctocolectomy more frequently (21 [78%] versus 6 [22%] P < 0.001) and were more likely to have mucinous tumors (11 [40.7%] versus 12 [22.3%] P = 0.03). Overall 3-y survival was significantly reduced in CARC patients compared with patients with sporadic rectal cancer. Those with CARC undergoing segmental proctectomy only demonstrated reduced overall and disease-free survival compared to patients with sporadic rectal cancer and to colitis patients undergoing proctocolectomy (P = 0.002). CONCLUSIONS: Patients with CARC undergoing proctectomy demonstrate reduced disease-free survival versus those undergoing proctocolectomy, and versus patients with sporadic rectal cancer undergoing proctectomy. These findings warrant further study and suggest that proctocolectomy should be considered the preferred surgical approach for CARC.

Watch and Wait: Is Surgery Always Necessary for Rectal Cancer?

OPINION STATEMENT: Despite decades of high-quality research, the treatment of rectal cancer remains a work in progress. The interplay between chemotherapy, radiotherapy, and surgery is under constant rearrangement and refinement. Through this all, the desire to preserve the anal sphincters and quality of life remains at the forefront. In the past decade, standard of care for stage II or III rectal cancers in the USA has been neoadjuvant chemoradiation therapy (CRT) followed by radical surgical resection of the rectum. While timing and sequence of the CRT continues to evolve, surgical resection has remained essential in treatment. This stands in contrast to anal cancer, where surgery is reserved purely for salvage. This article describes a treatment strategy that attempts to treat rectal adenocarcinoma with CRT alone, reserving surgery for failure or salvage. Of the studies performed to date, a number are methodologically sound and show promise. However, the body of evidence has yet to reach a size to sway practitioners from the established trinity of chemotherapy, radiotherapy, and surgery. Interestingly, few trials administer post treatment full-dose systemic chemotherapy, which is the standard of care in patients undergoing surgical resection. Better identification of patients that will have complete cure from this approach, combined with long-term outcome data on salvage patients, is necessary for this therapy to be universally embraced.

Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial.

BACKGROUND: Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. METHODS: We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II-III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m(2) per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6-8 weeks after chemoradiation. Patients in groups 2-4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m(2) or 400 mg/m(2), according to the discretion of the treating investigator, oxaliplatin 85 mg/m(2) in a 2-h infusion, bolus fluorouracil 400 mg/m(2) on day 1, and a 46-h infusion of fluorouracil 2400 mg/m(2). The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816. FINDINGS: Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10-30) of 60 patients in group 1, 17 (25%, 16-37) of 67 in group 2, 20 (30%, 19-42) of 67 in group 3, and 25 (38%, 27-51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39-8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2-4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients). INTERPRETATION: Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials. FUNDING: National Institutes of Health National Cancer Institute.

Acute health care resource utilization for ileostomy patients is higher than expected.

BACKGROUND: Patients requiring an ileostomy following colorectal surgery are at risk for increased health-care utilization after discharge. Prior studies evaluating postoperative ileostomy care may underestimate health-care utilization by reporting only "same-institution" readmission rates. OBJECTIVE: The aim of this study was to determine the rates of health-care utilization of new ostomates within 30 days of discharge in a multicenter environment. DESIGN: This is a retrospective cohort study. SETTINGS: This study was conducted at acute-care, community hospitals in California, Florida, Nebraska, and New York. PATIENTS: Adult patients who underwent colorectal surgery with primary anastomosis, colostomy, or ileostomy between July 2009 and September 2010 were identified. MAIN OUTCOME MEASURES: The primary outcome measured was hospital-based acute care, defined as hospital readmission or emergency department visit, at any hospital within 30 days of surgery. Multivariate regression models were used to compare the outcomes across groups. RESULTS: Overall, 75,136 patients underwent colectomy with most receiving a primary anastomosis (79.3%), whereas colostomies were created in 12.8% and ileostomies were created in 8.0%. Diagnoses of colorectal cancer (36.1%) or diverticular disease (22.0%) were most common. Patients with a colostomy (18.8%; adjusted odds ratio [AOR], 1.23 [95% CI, 1.17-1.30]) or ileostomy (36.1%; AOR, 2.28 [95% CI 2.15-2.42]) were significantly more likely than patients with a primary anastomosis (16.2%) to have a hospital-based acute-care encounter within 30 days of discharge. Among patients undergoing ileostomy, postoperative infection, renal failure, and dehydration were the most common diagnoses for hospital-based acute-care events. Overall, 20% of these encounters occurred at hospitals other than where the index surgery occurred. LIMITATIONS: Coding accuracy, the inability to capture events occurring in physician offices, and the retrospective study design were limitations of the study. CONCLUSIONS: Patients undergoing colorectal surgery with an ileostomy return to the hospital after discharge twice as frequently as those with a primary anastomosis or colostomy, often to hospitals other than the primary institution. As postdischarge health-care utilization becomes a measured quality metric, it is increasingly important to help these patients to safely transition to home.

Accordion complication grading predicts short-term outcome after right colectomy.

BACKGROUND: The Accordion severity grading system is a novel system to score the severity of postoperative complications in a standardized fashion. This study aims to demonstrate the validity of the Accordion system in colorectal surgery by correlating severity grades with short-term outcomes after right colectomy for colon cancer. METHODS: This is a retrospective cohort review of patients who underwent right colectomy for cancer between January 1, 2002, and January 31, 2007, at a single tertiary care referral center. Complications were categorized according to the Accordion severity grading system: grades 1 (mild), 2 (moderate), 3-5 (severe), and 6 (death). Outcome measures were hospital stay, 30-d readmission rate and 1-y survival. Correlation between Accordion grades and outcome measures is reflected by Spearman rho (ρ). One-year survival was obtained per Kaplan-Meier method and compared by logrank test for trend. Significance was set at P ≤ 0.05. RESULTS: Overall, 235 patients underwent right colectomy for cancer of which 122 (51.9%) had complications. In total, 52 (43%) had an Accordion grade 1 complication; 44 (36%) grade 2; four (3%) grade 3; 11 (9%) grade 4; seven (6%) grade 5; and four (3%) grade 6. There was significant correlation between Accordion grades and hospital stay (ρ = 0.495, P < 0.001) and 30-d readmission rate (ρ = 0.335, P < 0.001). There was a significant downward trend in 1-y survival as complication severity by Accordion grade increased (P = 0.02). CONCLUSIONS: The Accordion grading system is a useful tool to estimate short-term outcomes after right colectomy for cancer. High-grade Accordion complications are associated with longer hospital stay and increased risk of readmission and mortality.