Executive Summary of the American Radium Society on Appropriate Use Criteria for Nonoperative Management of Rectal Adenocarcinoma: Systematic Review and Guidelines.

For patients with rectal cancer, the standard approach of chemotherapy, radiation therapy, and surgery (trimodality therapy) is associated with significant long-term toxicity and/or colostomy for most patients. Patient options focused on quality of life (QOL) have dramatically improved, but there remains limited guidance regarding comparative effectiveness. This systematic review and associated guidelines evaluate how various treatment strategies compare to each other in terms of oncologic outcomes and QOL. Cochrane and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology were used to search for prospective and retrospective trials and meta-analyses of adequate quality within the Ovid Medline database between January 1, 2012, and June 15, 2023. These studies informed the expert panel, which rated the appropriateness of various treatments in 6 clinical scenarios through a well-established consensus methodology (modified Delphi). The search process yielded 197 articles that advised voting. Increasing data have shown that nonoperative management (NOM) and primary surgery result in QOL benefits noted over trimodality therapy without detriment to oncologic outcomes. For patients with rectal cancer for whom total mesorectal excision would result in permanent colostomy or inadequate bowel continence, NOM was strongly recommended as usually appropriate. Restaging with tumor response assessment approximately 8 to 12 weeks after completion of radiation therapy/chemoradiation therapy was deemed a necessary component of NOM. The panel recommended active surveillance in the setting of a near-complete or complete response. In the setting of NOM, 54 to 56 Gy in 27 to 31 fractions concurrent with chemotherapy and followed by consolidation chemotherapy was recommended. The panel strongly recommends primary surgery as usually appropriate for a T3N0 high rectal tumor for which low anterior resection and adequate bowel function is possible, with adjuvant chemotherapy considered if N+. Recent data support NOM and primary surgery as important options that should be offered to eligible patients. Considering the complexity of multidisciplinary management, patients should be discussed in a multidisciplinary setting, and therapy should be tailored to individual patient goals/values.

Organ Preservation and Survival by Clinical Response Grade in Patients With Rectal Cancer Treated With Total Neoadjuvant Therapy: A Secondary Analysis of the OPRA Randomized Clinical Trial.

Importance: Assessing clinical tumor response following completion of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer is paramount to select patients for watch-and-wait treatment. Objective: To assess organ preservation (OP) and oncologic outcomes according to clinical tumor response grade. Design, Setting, and Participants: This was secondary analysis of the Organ Preservation in Patients with Rectal Adenocarcinoma trial, a phase 2, nonblinded, multicenter, randomized clinical trial. Randomization occurred between April 2014 and March 2020. Eligible participants included patients with stage II or III rectal adenocarcinoma. Data analysis occurred from March 2022 to July 2023. Intervention: Patients were randomized to induction chemotherapy followed by chemoradiation or chemoradiation followed by consolidation chemotherapy. Tumor response was assessed 8 (±4) weeks after TNT by digital rectal examination and endoscopy and categorized by clinical tumor response grade. A 3-tier grading schema that stratifies clinical tumor response into clinical complete response (CCR), near complete response (NCR), and incomplete clinical response (ICR) was devised to maximize patient eligibility for OP. Main Outcomes and Measures: OP and survival rates by clinical tumor response grade were analyzed using the Kaplan-Meier method and log-rank test. Results: There were 304 eligible patients, including 125 patients with a CCR (median [IQR] age, 60.6 [50.4-68.0] years; 76 male [60.8%]), 114 with an NCR (median [IQR] age, 57.6 [49.1-67.9] years; 80 male [70.2%]), and 65 with an ICR (median [IQR] age, 55.5 [47.7-64.2] years; 41 male [63.1%]) based on endoscopic imaging. Age, sex, tumor distance from the anal verge, pathological tumor classification, and clinical nodal classification were similar among the clinical tumor response grades. Median (IQR) follow-up for patients with OP was 4.09 (2.99-4.93) years. The 3-year probability of OP was 77% (95% CI, 70%-85%) for patients with a CCR and 40% (95% CI, 32%-51%) for patients with an NCR (P < .001). Clinical tumor response grade was associated with disease-free survival, local recurrence-free survival, distant metastasis-free survival, and overall survival. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, most patients with a CCR after TNT achieved OP, with few developing tumor regrowth. Although the probability of tumor regrowth was higher for patients with an NCR compared with patients with a CCR, a significant proportion of patients achieved OP. These findings suggest the 3-tier grading schema can be used to estimate recurrence and survival outcomes in patients with locally advanced rectal cancer who receive TNT. Trial Registration: ClinicalTrials.gov Identifier: NCT02008656.

Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.

Cost Drivers of Elective Colon and Rectal Surgery: A Retrospective Cohort Analysis.

BACKGROUND: Colorectal surgery is expensive. Few studies have evaluated complications as an economic cost driver, and there is little evidence comparing multiple cost drivers of colorectal surgery to determine the most effective means of reducing total cost. OBJECTIVE: This study aimed to determine the effects of surgical techniques, use of enhanced recovery protocols, and presence or absence of complications on the total cost of hospitalization for elective colorectal surgery. DESIGN: A retrospective cohort analysis using data from 2011 to 2018 was performed. The primary end point was a mean cost per hospitalization. The cost was compared between patients who experienced minimally invasive versus open surgeries, enhanced recovery after surgery protocols versus not, and complications versus none. SETTINGS: This study was conducted at a university-affiliated teaching hospital in the Northeastern United States. PATIENTS: Adult patients who have undergone elective colorectal surgery were included. MAIN OUTCOME MEASURES: The primary outcome for this study was the mean cost per hospitalization calculated using inpatient cost based on the total cost of the episode of care. RESULTS: A total of 1039 patients met the criteria for inclusion. The average cost of all hospitalizations was $19,801. Multivariate analysis demonstrated that enhanced recovery protocols substantially lowered the cost of care by $6392 ( p = 0.001), whereas complications increased the cost of care by $16,780 per episode ( p < 0.001). When complications occurred, enhanced recovery protocols reduced the cost by $17,963 ( p = 0.010). LIMITATIONS: This retrospective cohort study performed at a single institution has inherent limitations, including confounding and selection bias. CONCLUSIONS: For elective colorectal surgery, complications are associated with significantly increased costs. Avoiding complications should be a priority to reduce costs. Enhanced recovery protocols are associated with significantly reduced costs. Surgeons should focus future research efforts on improving protocols and processes that decrease postoperative complications to improve patient outcomes and to reduce costs associated with elective colorectal hospitalizations. See Video Abstract at http://links.lww.com/DCR/B927 . FACTORES DE COSTO DE LA CIRUGA ELECTIVA DE COLON Y RECTO UN ANLISIS DE COHORTE RETROSPECTIVE: ANTECEDENTES:La cirugía colorrectal es costosa. Pocos estudios han examinado las complicaciones como un factor de costo económico, y hay poca evidencia que compare múltiples factores de costo de la cirugía colorrectal para determinar los medios más efectivos para reducir el costo total.OBJETIVO:Este estudio tiene como objetivo determinar los efectos de las técnicas quirúrgicas, el uso de protocolos de enhanced recovery y la presencia o ausencia de complicaciones en el costo total de hospitalización por cirugía colorrectal electiva.DISEÑO:Se realizó un análisis retrospectivo de cohortes utilizando data del 2011-2018. El punto principal fue el costo medio por hospitalización. Se comparó el costo entre los pacientes que experimentaron: cirugías mínimamente invasivas versus abiertas, protocolos de enhanced recovery después de la cirugía versus no, y complicaciones versus no.FUENTE DE DATOS:Se consultó la base de datos financiera y contable del hospital y el registro médico electrónico para la obtencion de datos.ENTORNO CLINICO:Este estudio se realizó en un hospital docente afiliado a una universidad en el noreste de los Estados Unidos.PACIENTES:Se incluyeron pacientes adultos sometidos a cirugía colorrectal electiva.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal de este estudio fue el costo medio por hospitalización calculado utilizando el costo de hospitalización basado en el costo total del episodio de atención.RESULTADOS:Un total de 1.039 pacientes cumplieron los criterios de inclusión. El costo promedio de todas las hospitalizaciones fue de $19801. El análisis multivariante demostró que los protocolos de enhanced recovery redujeron sustancialmente el costo de la atención en $6392 ( p = 0,001), mientras que las complicaciones aumentaron el costo en $16780 por episodio ( p < 0,001). Cuando ocurrieron complicaciones, los protocolos de enhanced recovery redujeron el costo en $17963 ( p = 0,010).LIMITACIONES:Este es un estudio de cohorte retrospectivo realizado en una sola institución y tiene limitaciones inherentes que incluyen confusión y sesgo de selección.CONCLUSIONES:Video Resumen en http://links.lww.com/DCR/B927 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy.

PURPOSE: Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited. METHODS: In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival. RESULTS: Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates. CONCLUSION: Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.

The Potential for Overtreatment With Total Neoadjuvant Therapy (TNT): Consider One Local Therapy Instead.

With increased therapeutic options in rectal cancer, a central question has become how to tailor therapy to patient preferences to avoid both over and under treatment. Total Neoadjuvant Therapy (TNT), defined as delivering all planned chemotherapy and radiation therapy (RT) before surgery, was developed with the primary goal of improving overall survival through early elimination of micrometastatic disease. In this narrative review assessing patients with operable adenocarcinoma of the rectum, we sought to evaluate TNT versus alternative options with regard to both quality of life (QoL) and oncologic outcomes. Survey data of patient preferences reveal that an increased focus on QoL when discussing options is essential. While evidence favors TNT improving distant metastases-free survival, this has not yet translated to a clear OS benefit. The improved pathologic complete response rate with TNT compared to short course RT or chemoradiation alone suggests proceeding to surgery might result in overtreatment, lending support to a watch-and-wait option for patients with a goal for nonoperative management if a clinical complete response is achieved. Similarly, for select low-risk patients, surgery may be the only local therapy required allowing for safe omission of RT. In the treatment of rectal cancer, the future appears to be moving toward one local therapy. As an alternative to TNT, there is growing support for the concept we define herein as total definitive therapy instead: chemoradiation followed by consolidation chemotherapy, saving surgery only for incomplete responders rather than as part of the initial treatment plan. Also, selective use of RT should be considered for low-risk patients. By thoroughly assessing how these treatment de-escalation options compare to more traditional treatment algorithms, this narrative review provides guidance on how to honor patient preferences for QoL by avoiding treatments that might offer negligible benefits in oncologic outcomes.

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.

Patient Perceptions and Quality of Life After Colon and Rectal Surgery: What Do Patients Really Want?

BACKGROUND: Colorectal surgery outcomes must be accurately assessed and aligned with patient priorities. No study to date has investigated the patient's subjective assessment of outcomes most important to them during and following their surgical recovery. Although surgeons greatly value the benefits of laparoscopy, patient priorities remain understudied. OBJECTIVE: This study aimed to assess what aspects of patients' perioperative care and recovery they value most when queried in the postoperative period. DESIGN: This study is an exploratory cross-sectional investigation of a defined retrospective patient population. Enrollees were stratified into subcategories and analyzed, with statistical analysis performed via χ test and unpaired t test. SETTINGS: This study was conducted at a single academic medical center in New England. PATIENTS: Patients who underwent a colorectal surgical resection between 2009 and 2015 were selected. INTERVENTIONS: Patients within a preidentified population were asked to voluntarily complete a 32-item questionnaire regarding their surgical care. MAIN OUTCOME MEASURES: The primary outcomes measured were patient perioperative and postoperative quality of life and satisfaction on selected areas of functioning. RESULTS: Of 167 queried respondents, 92.2% were satisfied with their recovery. Factors considered most important included being cured of colorectal cancer (76%), not having a permanent stoma (78%), and avoiding complications (74%). Least important included length of stay (13%), utilization of laparoscopy (14%), and incision appearance and length (2%, 4%). LIMITATIONS: The study had a relatively low response rate, the study is susceptible to responder's bias, and there is temporal variability from surgery to questionnaire within the patient population. CONCLUSIONS: Overall, patients reported high satisfaction with their care. Most important priorities included being free of cancer, stoma, and surgical complications. In contrast, outcomes traditionally important to surgeons such as laparoscopy, incision appearance, and length of stay were deemed less important. This research helps elucidate the outcomes patients truly consider valuable, and surgeons should focus on these outcomes when making surgical decisions. See Video Abstract at http://links.lww.com/DCR/A596. See Visual Abstract at https://tinyurl.com/yb25xl66.

Preemptive Analgesia Decreases Pain Following Anorectal Surgery: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND: Postoperative pain is a frequent cause for delayed discharge following outpatient procedures, including anorectal surgery. Both central and peripheral pain receptor sensitization are thought to contribute to postoperative pain. Blocking these receptors and preempting sensitization prevents hyperalgesia leading to lower pain medication requirements. Studies in the orthopedic, urologic, and gynecologic literature support this practice, but the use of preemptive analgesia in anorectal surgery is understudied. OBJECTIVE: This study aimed to evaluate the effectiveness of preemptive analgesia in decreasing postoperative pain. DESIGN: This is a randomized, double-blinded, placebo-controlled trial. SETTING: This study was conducted at the University of Vermont Medical Center, a tertiary care referral center in Burlington, Vermont. PATIENTS: Patients who were over 18 years of age, ASA Physical Status Classes I, II, or III, and undergoing surgery for anal fissure, fistula or condyloma or hemorrhoids were selected. INTERVENTIONS: Preoperative oral acetaminophen and gabapentin followed by intravenous ketamine and dexamethasone were given before incision compared with oral placebos. MAIN OUTCOME MEASURES: The primary outcomes measured were postoperative pain scores, percentage of patients utilizing breakthrough narcotics, and rates of side effects. RESULTS: Ninety patients were enrolled. Because of patient withdrawal, screen failures, and loss to follow-up, 61 patients were analyzed (30 in the preemptive analgesia group and 31 in the control group). Patients in the active group had significantly less pain in the postanesthesia care unit and at 8 hours postoperatively. Significantly fewer participants in the active group used narcotics in the postanesthesia care unit and at 8 hours postoperatively. Average pain scores were excellent for both groups. There was no difference in the number of medication-related side effects between the 2 groups. LIMITATIONS: This study was limited by the small sample size and excellent pain control in both groups. CONCLUSIONS: Preemptive analgesia is safe and results in decreased pain in the early postoperative period following anorectal surgery. It should be implemented by surgeons performing these procedures. See Video Abstract at http://links.lww.com/DCR/A588.

Technical Considerations in Stoma Creation.

Creating an intestinal stoma is commonly the final aspect of an often emergent and complicated operation under difficult circumstances. While creation of a protruding, tension-free, and well-vascularized stoma is often straightforward, one must be prepared for challenging situations such as a thick abdominal wall and short, thickened mesentery. A successful stoma starts with attentive preoperative planning including site marking, thoughtful consideration of alternatives, and attention to technical detail. The tips provided in this article should facilitate the process of selecting the appropriate intestinal segment, identifying the correct stoma site, and creating a functional stoma even in the most challenging situations. Constructing a high-quality stoma will decrease complications and improve the patient's quality of life. Stoma creation is frequently the only component of an operation that the patient will have to live with for the remainder of his/her life.

Transanal Endoscopic Microsurgery for Early Rectal Cancer: A Single-Center Experience.

BACKGROUND: There is debate regarding the appropriate use of transanal endoscopic microsurgery for rectal cancer. OBJECTIVE: This study analyzed our single-center experience with transanal endoscopic microsurgery for early rectal cancer. DESIGN: Medical charts of patients who underwent transanal endoscopic microsurgery were reviewed to determine lesion characteristics, as well as operative and treatment characteristics. Complications and recurrences were recorded. SETTINGS: The study was conducted at a single academic medical center. PATIENTS: Patients with early stage cancer (T1 or T2, N0, and M0) of the rectum were included. MAIN OUTCOME MEASURES: Local and overall recurrence and disease-specific survival were measured. RESULTS: A total of 92 patients were analyzed. Median follow-up was 4.6 years. Negative margins were obtained in 98.9%. Length of stay was 1 day for 95.4% of patients. The complication rate was 10.9% (n = 10), including urinary retention at 4.3% (n = 4) and postoperative bleeding at 4.3% (n = 4). Preoperative staging included 54 at T1 (58.7%) and 38 at T2 (41.3%). Adjuvant therapy was recommended for all of the T2 and select T1 lesions with adverse features on histology. The final pathologic stages of tumors were ypT0 at 8.7% (n = 8), pT1 at 58.7% (n = 54), pT2 at 23.9% (n = 22), and ypT2 at 8.7% (n = 8). The 3-year local recurrence risk was 2.4% (SE = 1.7), and overall recurrence was 6.7% (SE = 2.9). There were no recurrences among patients with complete pathologic response to neoadjuvant therapy. Mean time to recurrence was 2.5 years (SD = 1.43). A total of 89.2% of patients with very low tumors underwent curative resection without a permanent stoma (33/37). The 3-year disease-specific survival rate was 98.6% (95% CI, 90.4%-99.8%), and overall survival rate was 89.4% (95% CI, 79.9%-94.6%). LIMITATIONS: The study was limited by its single-center retrospective experience. CONCLUSIONS: Transanal endoscopic microsurgery provides comparable oncologic outcomes to radical resection in properly selected patients with early rectal cancer. Sphincter preservation rates approach 90% even in patients with very distal rectal cancer.

Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial.

BACKGROUND: Local excision is an organ-preserving treatment alternative to transabdominal resection for patients with stage I rectal cancer. However, local excision alone is associated with a high risk of local recurrence and inferior survival compared with transabdominal rectal resection. We investigated the oncological and functional outcomes of neoadjuvant chemoradiotherapy and local excision for patients with stage T2N0 rectal cancer. METHODS: We did a multi-institutional, single-arm, open-label, non-randomised, phase 2 trial of patients with clinically staged T2N0 distal rectal cancer treated with neoadjuvant chemoradiotherapy at 26 American College of Surgeons Oncology Group institutions. Patients with clinical T2N0 rectal adenocarcinoma staged by endorectal ultrasound or endorectal coil MRI, measuring less than 4 cm in greatest diameter, involving less than 40% of the circumference of the rectum, located within 8 cm of the anal verge, and with an Eastern Cooperative Oncology Group performance status of at least 2 were included in the study. Neoadjuvant chemoradiotherapy consisted of capecitabine (original dose 825 mg/m(2) twice daily on days 1-14 and 22-35), oxaliplatin (50 mg/m(2) on weeks 1, 2, 4, and 5), and radiation (5 days a week at 1·8 Gy per day for 5 weeks to a dose of 45 Gy, followed by a boost of 9 Gy, for a total dose of 54 Gy) followed by local excision. Because of adverse events during chemoradiotherapy, the dose of capecitabine was reduced to 725 mg/m(2) twice-daily, 5 days per week, for 5 weeks, and the boost of radiation was reduced to 5·4 Gy, for a total dose of 50·4 Gy. The primary endpoint was 3-year disease-free survival for all eligible patients (intention-to-treat population) and for patients who completed chemotherapy and radiation, and had ypT0, ypT1, or ypT2 tumours, and negative resection margins (per-protocol group). This study is registered with ClinicalTrials.gov, number NCT00114231. FINDINGS: Between May 25, 2006, and Oct 22, 2009, 79 eligible patients were recruited to the trial and started neoadjuvant chemoradiotherapy. Two patients had no surgery and one had a total mesorectal excision. Four additional patients completed protocol treatment, but one had a positive margin and three had ypT3 tumours. Thus, the per-protocol population consisted of 72 patients. Median follow-up was 56 months (IQR 46-63) for all patients. The estimated 3-year disease-free survival for the intention-to-treat group was 88·2% (95% CI 81·3-95·8), and for the per-protocol group was 86·9% (79·3-95·3). Of 79 eligible patients, 23 (29%) had grade 3 gastrointestinal adverse events, 12 (15%) had grade 3-4 pain, and 12 (15%) had grade 3-4 haematological adverse events during chemoradiation. Of the 77 patients who had surgery, six (8%) had grade 3 pain, three (4%) had grade 3-4 haemorrhage, and three (4%) had gastrointestinal adverse events. INTERPRETATION: Although the observed 3-year disease free survival was not as high as anticipated, our data suggest that neoadjuvant chemoradiotherapy followed by local excision might be considered as an organ-preserving alternative in carefully selected patients with clinically staged T2N0 tumours who refuse, or are not candidates for, transabdominal resection. FUNDING: National Cancer Institute and Sanofi-Aventis.

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.

A novel approach to assessing technical competence of colorectal surgery residents: the development and evaluation of the Colorectal Objective Structured Assessment of Technical Skill (COSATS).

OBJECTIVE: To develop and evaluate an objective method of technical skills assessment for graduating subspecialists in colorectal (CR) surgery-the Colorectal Objective Structured Assessment of Technical Skill (COSATS). BACKGROUND: It may be reasonable for the public to assume that surgeons certified as competent have had their technical skills assessed. However, technical skill, despite being the hallmark of a surgeon, is not directly assessed at the time of certification by surgical boards. METHODS: A procedure-based, multistation technical skills examination was developed to reflect a sample of the range of skills necessary for CR surgical practice. These consisted of bench, virtual reality, and cadaveric models. Reliability and construct validity were evaluated by comparing 10 graduating CR residents with 10 graduating general surgery (GS) residents from across North America. Expert CR surgeons, blinded to level of training, evaluated performance using a task-specific checklist and a global rating scale. The mean global rating score was used as the overall examination score and a passing score was set at "borderline competent for CR practice." RESULTS: The global rating scale demonstrated acceptable interstation reliability (0.69) for a homogeneous group of examinees. Both the overall checklist and global rating scores effectively discriminated between CR and GS residents (P < 0.01), with 27% of the variance attributed to level of training. Nine CR residents but only 3 GS residents were deemed competent. CONCLUSIONS: The Colorectal Objective Structured Assessment of Technical Skill effectively discriminated between CR and GS residents. With further validation, the Colorectal Objective Structured Assessment of Technical Skill could be incorporated into the colorectal board examination where it would be the first attempt of a surgical specialty to formally assess technical skill at the time of certification.

A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial.

PURPOSE: We designed American College of Surgeons Oncology Group (ACOSOG) Z6041, a prospective, multicenter, single-arm, phase II trial to assess the efficacy and safety of neoadjuvant chemoradiation (CRT) and local excision (LE) for T2N0 rectal cancer. Here, we report tumor response, CRT-related toxicity, and perioperative complications (PCs). METHODS: Clinically staged T2N0 rectal cancer patients were treated with capecitabine and oxaliplatin during radiation followed by LE. Because of toxicity, capecitabine and radiation doses were reduced. LE was performed 6 weeks after CRT. Patients were evaluated for clinical and pathologic response. CRT-related complications and PCs were recorded. RESULTS: Ninety patients were accrued; 6 received nonprotocol treatment. The remaining 84 were 65% male; median age 63 years; 83% Eastern Cooperative Oncology Group performance score 0; 92% white; mean tumor size 2.9 cm; and average distance from anal verge 5.1 cm. Five patients were considered ineligible. Therapy was completed per protocol in 79 patients, but two patients did not undergo LE. Among 77 eligible patients who underwent LE, 34 patients achieved a pathologic complete response (44%) and 49 (64%) tumors were downstaged (ypT0-1), but 4 patients (5%) had ypT3 tumors. Five LE specimens contained lymph nodes; one T3 tumor had a positive node. All but one patient had negative margins. Thirty-three (39%) of 84 patients developed CRT-related grade ≥3 complications. Rectal pain was the most common PC. CONCLUSIONS: CRT before LE for T2N0 tumors results in a high pathologic complete response rate and negative resection margins. However, complications during CRT and after LE are high. The true efficacy of this approach will ultimately be assessed by the long-term oncologic outcomes.

Identification of a biomarker profile associated with resistance to neoadjuvant chemoradiation therapy in rectal cancer.

OBJECTIVE: To identify a biomarker profile associated with tumor response to chemoradiation (CRT) in locally advanced rectal cancer. BACKGROUND: Rectal cancer response to neoadjuvant CRT is variable. Whereas some patients have a minimal response, others achieve a pathologic complete response (pCR) and have no viable cancer cells in their surgical specimens. Identifying biomarkers of response will help select patients more likely to benefit from CRT. METHODS: This study includes 132 patients with locally advanced rectal cancer treated with neoadjuvant CRT followed by surgery. Tumor DNA from pretreatment tumor biopsies and control DNA from paired normal surgical specimens was screened for mutations and polymorphisms in 23 genes. Genetic biomarkers were correlated with tumor response to CRT (pCR vs non-pCR), and the association of single or combined biomarkers with tumor response was determined. RESULTS: Thirty-three of 132 (25%) patients achieved a pCR and 99 (75%) patients had non-pCR. Three individual markers were associated with non-pCR; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutation (P = 0.0145), cyclin D1 G870A (AA) polymorphism (P = 0.0138), and methylenetetrahydrofolate reductase (NAD(P)H) C677T (TT) polymorphism (P = 0.0120). Analysis of biomarker combinations revealed that none of the 27 patients with both tumor protein p53 (p53) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations had a pCR. Further, in patients with both p53 and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations or the cyclin D1 G870A (AA) polymorphism or the methylenetetrahydrofolate reductase (NAD(P)H) C677T (TT) polymorphism (n = 52) the association with non-pCR was further strengthened; 51 of 52 (98%) of patients were non-pCR. These biomarker combinations had a validity of more than 70% and a positive predictive value of 97% to 100%, predicting that patients harboring these mutation/polymorphism profiles will not achieve a pCR. CONCLUSIONS: A specific biomarker profile is strongly associated with non-pCR to CRT and could be used to select optimal oncologic therapy in rectal cancer patients. ClinicalTrials.org Identifier: NCT00335816.

The high yield of 1-year colonoscopy after resection: is it the handoff?

BACKGROUND: This study aimed to determine the diagnostic yield of colonoscopy 1 year after colorectal cancer (CRC) resection based on whether the index colonoscopy was performed by the operating surgeon. METHODS: All patients undergoing surgery for colorectal cancer by two colon and rectal surgeons at a university hospital from 1991 to 2005 were identified from the tumor registry. Those patients with a complete preoperative colonoscopy by any physician and a 1-year follow-up examination by the operating surgeon were selected for the study population. Family history of colorectal cancer, tumor location, endoscopist, presence of synchronous neoplasms, and findings of 1-year colonoscopy were recorded. Fisher's exact test was used to compare the probability of finding any adenoma, advanced adenoma, or invasive cancer based on the index endoscopist. RESULTS: Of the 719 patients who underwent resection during the study period, 432 met the inclusion criteria. The index colonoscopy for 117 of these patients (27.1%) was performed by one of the two surgeons. Overall, 10 patients (2.3%) had a "new" cancer diagnosed at 1 year, and 1 patient (0.2%) had a local recurrence. Patients whose index colonoscopy was performed by their operating surgeon appeared less likely to have an advanced lesion found at 1 year (5.1% vs 11.4%; p = 0.06). The index colonoscopy for 9 of the 10 of cancers found at 1 year was not performed by the operating surgeon. CONCLUSIONS: Colonoscopy 1 year after CRC resection is clearly justified. An index colonoscopy by the operating surgeon eliminates a "handoff" and may diminish the incidence of high-risk lesions at 1 year.

Anastomotic leaks after bowel resection: what does peer review teach us about the relationship to postoperative mortality?

BACKGROUND: Anastomotic leak is a dreaded complication of intestinal surgery and has been associated with a high mortality rate. But it is uncertain exactly which patient populations are at risk of death from the leak. We sought to assess the impact of surgeon volume on leak rate and to better understand the relationship of a leak to postoperative mortality. STUDY DESIGN: All adult patients having a small or large bowel resection with anastomosis at a university hospital from July 2003 to June 2006 were entered into a prospectively maintained quality database; data were entered by a specially trained nurse practitioner who rounded daily with housestaff. Patients with a postoperative leak based on standardized criteria were identified. Patient characteristics, surgical procedure, and operating surgeon were noted. Overall complication and leak rates by surgeon were compared using Fisher's exact test. Individual case review by a group of peers was performed for all patients with a leak who died, to determine the relationship to mortality. RESULTS: Five hundred fifty-six patients underwent resection with anastomosis during the study period. There were 27 patients with leaks (4.9%), 6 of whom died. Leak rate for the highest-volume surgeons ranged from 1.6% to 9.9% (p <0.01), and overall complication rate varied from 30.5% to 44% (p=0.04). In four of six deaths, leaks occurred in very ill patients undergoing emergency procedures and appeared to be premorbid events. In only one patient did the leak appear to be the primary cause of death. CONCLUSIONS: The variability in leak rate by surgeons doing similar operations suggests that many leaks may be preventable. But death after a leak is most often a surrogate for a critically ill patient and was infrequently the actual cause of death.