High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study

To evaluate patients with proximal rectal cancer (PRC) (> 6 cm up to 12 cm) and distal rectal cancer (DRC) (0 to 6 cm from the anal verge). Two hundred and eighteen patients (120 male, 98 female, median age 58 years, range 19-88 years) comprised 100 with PRC and 118 with DRC. The proportion of T1, T2 vs T3, T4 stage cancers was similar in both groups (PRC: T1+T2 = 29%; T3+T4 = 71% and DRC: T1+T2 = -31%; T3+T4 = 69%). All patients had cancer confined to the rectum - those with synchronous distant metastasis were excluded. Surgical resection was with curative intent with or without pre-operative chemoradiation (c-RT). Follow-up was for a median of 35 mo (range: 12 to 126 mo). End points were: 30 d mortality, complications of operation, microscopic tumour- free margins, resection with a tumour-free circumferential margin (CRM) of 1 to 2 mm and > 2 mm, local recurrence, survival and the permanent stoma rate. Overall 30-d mortality was 6% (12): PRC 7 % and DRC 4%. Postoperative complications occurred in 14% with PRC compared with 21.5% with DRC, urinary retention was the complication most frequently reported (PRC 2% vs DRC 9%, P = 0.04). Twelve percent with PRC compared with 37% with DRC were subjected to preoperative c-RT (P = 0.03). A tumour-free CRM of 1 to 2 mm and > 2 mm was reported in 93% and 82% with PRC and 88% and 75% with DRC respectively (PRC vs DRC, P > 0.05). However, local recurrence was 5% for PRC vs 11% for DRC (P < 0.001). Three and five years survival was 65.6% and 60.2% for PRC vs 67% and 64.3% for DRC respectively. No patient with PRC and 23 (20%) with DRC received an abdomino-perineal resection. PRC and DRC differ in the rate of abdomino-perineal resection, post-operative urinary retention and local recurrence. Survival in both groups was similar.

Introduction: Robotic approach has been increasingly applied to the surgical resection of distal rectal cancer. All reports from the advocators on the use of robotic assistance in rectal s...

Watchful Waiting After Complete Clinical Response Following Concurrent Chemoradiation for Rectal Adenocarcinoma

Locally advanced rectal adenocarcinoma: Treatment sequences, intensification, and rectal organ preservation.

The principal goal in the management of any patient with rectal cancer is to provide the optimum chance for cure while maintaining their quality of life. Treatment options over the past century have reflected our ability to provide safe surgical care and, more recently, a greater understanding of tumor biology. Prior to the introduction of the abdominoperineal resection (APR) that was reported in the Lancet in 1908 by Sir Ernest Miles, perineal excision was the accepted approach for nearly all rectal cancer. Unfortunately, inconsistent surgical outcomes and high local recurrence even in Miles personal experience promoted alternative treatment. The acceptance of APR and subsequently low anterior resection reduced recurrence and improved long-term survival but often with the cost of decreased quality of life. A recent review by McCall et al. report disease specific recurrence at 8.5 percent, 16.3 percent and 28.6 percent for cancer stages I, II and III respectively with an overall reported recurrence rates following APR ranging from 10 to 29 percent. Reported five-year survival rates range 78 to 100 percent for stage I, 45 to 73 percent for stage II and 22 to 66 percent for stage III. The wide variations in recurrence and survival rates likely reflect differences in tumor size, proximity to the anal canal, depth of penetration in the rectal wall and unfavorable histologic characteristics. An additional confounding variable in the management of rectal cancer has been the use of adjuvant therapy do in part to the timing and dose/fractionation differences utilized. Given the variation in outcomes with APR and ongoing concerns regarding morbidity and quality of life issues associated with radical resection, many centers have revisited local therapy as a means of managing select patients with distal rectal cancers. These therapies include transanal and transcoccygeal excision as well as endocavitary radiation and even fulguration. It is the belief of many surgeons that our ability to more accurately stage patients preoperatively and add adjuvant therapy when indicated will improve our success with local excision.

For distal rectal tumors, abdominoperineal resection may achieve local control but with significant morbidity. High-dose radiation can improve pathologic response and allow for full-thickness local excision (FTLE) with comparable outcomes and improved morbidity. We report 15 years of data on distal rectal cancer treated with chemotherapy, intensity-modulated radiotherapy (IMRT), and FTLE via transanal endoscopic microsurgery. Forty-four patients were treated for cT1–T3, N0, and M0 distal rectal cancer using IMRT at 5580 cGy with 5-FU chemotherapy, followed by FTLE. Local recurrence (LR), disease-free survival (DFS), and overall survival (OS) were reported. Median follow-up was 51 months. Three patients (6.8%) had LR, all salvaged surgically. Mean DFS and OS are 8.56 and 9.10 years, respectively. DFS and OS were strongly associated with pathologic response to chemoradiotherapy (p = 0.043 and p = 0.023, respectively). Thirty-four patients (77%) are alive with no disease. Postoperative grade I–II complications noted in 17 patients and grade III complications in 2 patients. No patients required a diverting colostomy. High-dose IMRT and chemotherapy followed by FTLE to treat distal rectal cancers are well tolerated and effective. FTLE may improve outcomes and minimize complications in appropriately selected patients. Randomized clinical trials are needed to compare it with standard surgery.

e19374 Background: Chemoradiotheray (CR) followed by standard Surgical Resection (SR) is the standard treatment for distal locally-advanced rectal cancer (LARC) patients after a clinical compete response (cCR). Some novel approach suggested better functional results using robotic rectal resection (RRR) or avoiding surgical procedure, called Watch and Wait (WW) strategy. Methods: A Markov model-based, cost-utility analysis estimating mean costs and QALYs per patient was performed to compare SR, RRR and WW strategies for patients achieving a cCR to CRT. Rates of local regrowth, recurrence and distant metastasis were derived from series comparing WW to SR and from our previous comparative study of RRR versus SR. Lifetime incremental cost-utility ratio was calculated between strategies, and sensitivity analysis were performed to study model uncertainly. A willingness-to-pay of 30.000 per Quality Adjusted-Life Year (QALY) was used as a threshold to determine the most cost-effective treatment. Results: The base case 15-years cancer-specific survival was 93.5% (95% confidence interval [CI] 91.5-94.9] on a WW program, compared to 95.9% [95%CI 93.6-97.7] after RRR. WW was dominant relative to RRR with cost savings of $48,566.58 (95%CI $47,635.77 - $49,497.39 ) and incremental QALY of 7.47 (95%CI 1.46 – 7.48). WW was also dominant relative to LRR, with cost savings of $48,764.49 (95%CI $47,768.49 - $49,760.48 ) and incremental QALY of 7.44 (95%CI 7,43 – 7.45). WW remained dominant in sensitivity analysis unless the rate of SR fell to 73.0%). Conclusions: This study provides data of cost-effectiveness differences between SR, RRR, WW approaches in LARC after cCR, showing a benefit for WW.

This study aims to review the operative results and oncological outcomes of anterior resection for rectal and rectosigmoid cancer. Comparison was made between patients with total mesorectal excision (TME) for mid and distal cancer and partial mesorectal excision (PME) for proximal cancer, when a 4- to 5-cm mesorectal margin could be achieved. Risk factors for local recurrence and survival were also analyzed. Anterior resection has become the preferred treatment option rectal cancer. TME with sharp dissection has been shown to be associated with a low local recurrence rate. Controversies still exist as to the need for TME in more proximal tumor. Resection of primary rectal and rectosigmoid cancer was performed in 786 patients from August 1993 to July 2002. Of these, 622 patients (395 men and 227 women; median age, 67 years) underwent anterior resection. The technique of perimesorectal dissection was used. Patients with mid and distal rectal cancer were treated with TME while PME was performed for those with more proximal tumors. Prospective data on the postoperative results and oncological outcomes were reviewed. Risk factors for anastomotic leakage, local recurrence, and survival of the patients were analyzed with univariate and multivariate analysis. The median level of the tumor was 8 cm from the anal verge (range, 2.5-20 cm) and curative resection was performed in 563 patients (90.5%). TME was performed in 396 patients (63.7%). Significantly longer median operating time, more blood loss, and a longer hospital stay were found in patients with TME. The overall operative mortality and morbidity rates were 1.8% and 32.6%, respectively, and there were no significant differences between those of TME and PME. Anastomotic leak occurred in 8.1% and 1.3% of patients with TME and PME, respectively (P < 0.001). Independent factors for a higher anastomotic leakage rate were TME, the male gender, the absence of stoma, and the increased blood loss. The 5-year actuarial local recurrence rate was 9.7%. The advanced stage of the disease and the performance of coloanal anastomosis were independent factors for increased local recurrence. The 5-year cancer-specific survival was 74.5%. The independent factors for poor survival were the advanced stage of the disease and the presence of lymphovascular and perineural invasion. Anterior resection with mesorectal excision is a safe option and can be performed in the majority of patients with rectal cancer. The local recurrence rate was 9.7% and the cancer-specific survival was 74.5%. When the tumor requires a TME, this procedure is more complex and has a higher leakage rate than in those higher tumors where PME provides adequate mesorectal clearance. By performing TME in patients with mid and distal rectal cancer, the local control and survival of these patients are similar to those of patients with proximal cancers where adequate clearance can be achieved by PME.

Total mesorectal excision (TME) with intersphincteric resection and handsewn coloanal anastomosis (ISR-CAA) has been shown to be oncologically safe in patients with distal rectal cancer treated with preoperative chemoradiation. The introduction of the watch-and-wait (WW) strategy for rectal cancer patients with a clinical complete response to neoadjuvant therapy is changing the profile of patients undergoing TME surgery immediately following neoadjuvant treatment. The outcomes of ISR-CAA for patients with locally advanced rectal cancers not qualifying for WW have not been investigated. We conducted a retrospective analysis comparing the outcomes of ISR-CAA and abdominoperineal resection (APR) in patients with distal rectal cancer treated with neoadjuvant therapy and not qualifying for WW, at a comprehensive cancer center with an established WW program. The primary outcome was local recurrence-free survival. Sixty-seven patients had ISR-CAA and 79 had APR. Median follow-up was 61.1 months. The two groups were similar in sex, tumor stage, grade, and distance from the anal verge, but patients in the APR group were older on average. An R0 resection was achieved in 94% of ISR-CAA patients and 91% of APR patients. Patients in the ISR-CAA group had a lower 5-year rate of local recurrence-free survival (79% vs. 93%; p = 0.038) compared with the APR group; however, 5-year disease-free survival did not differ significantly between groups (67% for ISR-CAA and 64% for APR; p = 0.19). The local recurrence rate after ISR-CAA may be higher than after APR for patients without a clinical complete response to neoadjuvant therapy requiring TME surgery.

Jeopardizing cure and risking high local recurrence have served as arguments against sphincter-saving resection for patients with distal third rectal cancer. This prospective study examines and compares the local recurrence and survival rates in patients with distal third rectal cancer treated by either coloanal anastomosis or abdominoperineal resection. Between 1977 and 1993, 174 patients underwent coloanal anastomoses and 38 patients underwent abdominoperineal resection. All tumors were located 4 to 7 cm from the anal verge. One hundred ninety-three patients (91 percent) underwent rectal excision with a curative intent. Mean follow-up was 66 months after sphincter-saving resection and 65 months after abdominoperineal resection. Mean anastomotic height from the anal verge was 2.3 cm after sphincter-saving resection. Overall local recurrence rate was 7.9 percent after sphincter-saving resection and 12.9 percent after abdominoperineal resection. The five-year actuarial survival rate was 78 percent after sphincter-saving resection and 74 percent after abdominoperineal resection. Local recurrence and survival are not compromised in patients with distal third rectal cancer when treated by sphincter-saving resection, provided that oncologic principles are not violated. Coloanal anastomosis can be performed with an acceptable morbidity.

The American Society of Colon and Rectal Surgeons (ASCRS) is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines Committee is composed of society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus and to develop clinical practice guidelines based on the best available evidence. Although they are not proscriptive, these guidelines provide information on which decisions can be made and do not dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. These guidelines should not be deemed inclusive of all proper methods of care nor exclusive of methods of care reasonably directed toward obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient. STATEMENT OF THE PROBLEM Colorectal cancer remains the third most common cancer for both men and women, and the second leading cause of cancer-related deaths in the United States annually. It is projected that 145,600 new colorectal cancer cases will have been diagnosed and an estimated 51,020 deaths from colorectal cancer will have occurred in 2019.1 It is difficult to estimate statistics attributable specifically to rectal cancer because, historically, much of the reporting for rectal cancer has been combined with colon cancer as the single disease entity of "colorectal cancer."1 Overall, the incidence of colorectal cancer has declined over the past decades, largely because of risk factor modification and screening.2 However, the 18- to 50-year age group represents a unique cohort of patients in whom the incidence of rectal cancer has been increasing. In contrast to overall trends, rectal cancer incidence increased by 1.8% annually in younger adults between 1990 and 2013.1 In an effort to ensure that patients with rectal cancer receive appropriate care using a multidisciplinary approach, the ASCRS collaborated with a multispecialty effort to develop the National Accreditation Program in Rectal Cancer to create educational modules and a set of clinical standards focusing on program management, clinical services, and quality improvement regarding rectal cancer.3,4 Because rectal cancer management involves multiple disciplines working in conjunction with one another, the surgical guidelines presented here must be viewed within that context and represent only a portion of the treatment necessary for the optimal care of patients with rectal cancer. Colorectal cancer screening, bowel preparation, enhanced recovery pathways, surveillance after curative treatment, and prevention of thromboembolic disease, while relevant to the management of patients with rectal cancer, are beyond of the scope of these guidelines and are addressed in other guidelines.5–9 A guideline focusing on colorectal surgery and frailty is forthcoming. METHODOLOGY These guidelines are based on the last set of ASCRS Practice Parameters for the Management of Rectal Cancer published in 2013.10 A systematic search of MEDLINE, PubMed, Embase, and the Cochrane Database of Collected Reviews was performed from January 1, 2013 through January 15, 2020. Individual literature searches were conducted for each of the different sections of the guideline (Fig. 1). An additional limitation to core clinical journals was applied if the initial word combination search returned more than 500 articles. Directed searches using embedded references from primary articles were performed in selected circumstances. The 1812 screened articles were evaluated for their level of evidence, favoring clinical trials, meta-analysis/systematic reviews, comparative studies, and large registry retrospective studies over single institutional series, retrospective reviews, and peer-reviewed, observational studies. Additional references identified through embedded references and other sources as well as practice guidelines or consensus statements from relevant societies were also reviewed. A final list of 361 sources was evaluated for methodologic quality, the evidence base was examined, and a treatment guideline was formulated by the subcommittee for this guideline. The final grade of recommendation and level of evidence for each statement were determined using the Grades of Recommendation, Assessment, Development, and Evaluation system (Table 1). When agreement was incomplete regarding the evidence base or treatment guideline, consensus from the committee chair, vice chair, and 2 assigned reviewers determined the outcome. Members of the ASCRS Clinical Practice Guidelines Committee worked in joint production of these guidelines from inception to final publication. Recommendations formulated by the subcommittee were reviewed by the entire Clinical Practice Guidelines Committee. Final recommendations were approved by the ASCRS Executive Council. In general, each ASCRS Clinical Practice Guideline is updated every 5 years. No funding was received for preparing this guideline, and the authors have declared no competing interests related this material. This guideline conforms to the Appraisal of Guidelines for Research and Evaluation (AGREE) checklist.TABLE 1.: The GRADE system: grading recommendationsFIGURE 1.: PRISMA literature search flow sheet. CPG = Clinical Practice Guideline.Defining the Rectum The lower limit of the rectum is usually defined by the anorectal ring, an anatomic landmark palpable on physical examination or visible radiographically as the upper border of the anal sphincter and puborectalis muscles.11 The upper limit of the rectum has been variably defined by the splaying of the teniae coli, the sacral promontory, the proximal valve of Houston, or the level of the peritoneal reflection. A recent consensus conference defined the point of the sigmoid take-off (ie, the junction of the sigmoid mesocolon and mesorectum) as seen on cross-sectional imaging as the upper limit of the rectum.12 Given that the correlation among these landmarks is imperfect and the presence of all 3 valves of Houston is inconsistent, the upper limit of the rectum, from a clinical perspective, can be somewhat elusive. In practice, the location of a rectal cancer is most commonly assessed by the distance from its distal margin to the anal verge, defined as the beginning of the hair-bearing skin. Tumors within 15 cm of the anal verge are typically classified as rectal cancers, although the total length of the rectum can vary by body habitus and sex.11 PREOPERATIVE ASSESSMENT Evaluation 1. A cancer-specific history should be obtained eliciting disease-specific symptoms, associated symptoms, family history, and perioperative medical risk. Routine laboratory values, including CEA level, should also be evaluated, as indicated. Grade of recommendation: Strong recommendation based on moderate-quality evidence, 1B. A cancer-specific history remains a cornerstone of the preoperative evaluation. Bleeding, pain, or symptoms related to obstruction should be assessed to help determine the urgency and sequence of evaluation and intervention; this consideration is particularly relevant when neoadjuvant therapy is being considered. Urinary, sexual, and bowel function should be reviewed and symptoms indicative of malignant fistulas or severe radiating pain may alert the surgeon to locally advanced disease involving adjacent pelvic organs. The patient's medical fitness to undergo multimodality treatment should be assessed to guide treatment planning and perioperative management. A thorough discussion of perioperative risk stratification is beyond the scope of this guideline.13–15 A family history should typically document relevant premalignant lesions and cancers including details like the age at diagnosis and the lineage of affected first- and second-degree relatives. Patients should be asked about known predisposing hereditary cancer syndromes, prior genetic testing, and family ancestry or ethnicity that may be relevant.16 Patients with findings suggestive of an inherited susceptibility to colorectal cancer should typically be referred for genetic counseling. Guidelines on the management of patients with inherited colorectal cancer have been previously published.17,18 Routine laboratory bloodwork and a CEA level are part of the preoperative evaluation. The baseline CEA level before initiating elective treatment is prognostic of long-term survival and is used as a reference during posttherapy surveillance.19 Although CEA levels assessed at different time points during multimodality treatment can correlate with treatment response, CEA does not reliably predict pathologic response to neoadjuvant therapy.20–23 There is insufficient evidence to support the routine use of other tumor markers such as CA19-9 in the evaluation of patients with rectal cancer.24 2. As a part of a complete physical examination, the distance of the distal extent of the cancer from the anal verge and the cancer's relation to the sphincter complex should typically be assessed. Grade of recommendation: Strong recommendation based on low-quality evidence, 1C. Assessment of the relationship between the distal extent of the lesion to both the anorectal ring (ie, top of the sphincter complex) as well as the anal verge is essential for treatment planning and for evaluating the patient's candidacy for sphincter preservation and should ideally be performed before initiating neoadjuvant therapy, which may cause regression of the lesion. The distance should be assessed by digital examination and endoscopically (rigid proctoscopy may provide a more accurate measurement than flexible sigmoidoscopy). Endoscopic tattooing for purposes of anticipated intraoperative localization or to facilitate mucosal surveillance in the event of a clinical complete response may be helpful.25–29 3. Before elective treatment, the histological diagnosis of invasive adenocarcinoma should be confirmed, and patients should typically undergo a full colonic evaluation so the treatment plan can address synchronous pathology, as needed. Grade of recommendation: Strong recommendation based on moderate-quality evidence, 1B. It is important to confirm the histological diagnosis of invasive adenocarcinoma before initiating therapy in the elective setting, because rectal neoplasms of other histologies may be amenable to nonresectional or different multimodality treatment options.30 Because endoscopic biopsy may be nondiagnostic or incongruent with the clinical impression of invasive adenocarcinoma because of a sampling error, repeat endoscopic or operative biopsies may be required to establish the histological diagnosis for purposes of treatment planning. Operative excisional biopsy is typically not performed unless it is done as a curative-intent transanal full-thickness excision with adequate radial margins as discussed in detail later. Patients newly diagnosed with rectal cancer should typically undergo a full colon evaluation. Although the incidence of synchronous colorectal cancer is low, in the range of 1% to 3%, the incidence of synchronous adenomas or other polyps can be as high as 30%.31–34 Colonoscopy is a preferred evaluation method because it offers a therapeutic platform to treat synchronous polyps.35,36 In cases where a colonoscopy is not completed, for instance, due to an obstructing cancer, CT colonography may be used.37–40 Computed tomography colonography has been shown to be a superior diagnostic study compared with double-contrast barium enema among patients with symptoms suggestive of colorectal cancer and can detect synchronous lesions.41 In patients receiving neoadjuvant therapy, colonoscopy may be reattempted if there is sufficient tumor regression to permit passage of a colonoscope. If a preoperative colon evaluation is not performed, typically in cases where urgent intervention is needed for obstructing lesions, a complete colonoscopy should be planned postoperatively. Staging 1. Rectal cancer should typically be staged according to the American Joint Committee on Cancer TNM system before initiating treatment. Grade of recommendation: Strong recommendation based on moderate-quality evidence, 1B. Rectal cancer should be staged according to the TNM system before treatment, except when emergent surgery is required. The TNM system, as defined by the American Joint Committee on Cancer, describes the depth of local tumor invasion (T stage), the extent of regional lymph node involvement (N stage), and the presence of distant metastasis (M stage).42,43 Updated 8th edition staging definitions categorize lymph nodes harboring micrometastasis (clusters of 20 or more cancer cells or metastases measuring >0.2 mm and <2 mm in diameter) as N1 disease, the presence of tumor deposits (N1c disease) as stage III regardless of the status of the lymph nodes, and peritoneal metastases as M1c disease.42,43 Rectal cancer should be described by both its initial clinical stage (cTNM), which guides treatment decisions, as well as the final pathologic stage (pTNM), which can provide prognostic information.42 Clinical stage can be further prefixed to designate the staging modality used, including u for ultrasound, mr for MRI, and ct for CT scan. For patients treated with preoperative therapy, pathologic tumor response is reported as ypTNM.44,45 2. Rectal cancer protocol pelvic MRI is the preferred modality for locoregional clinical staging. Endorectal ultrasound (EUS) may be considered when differentiating between early T stages (ie, T1 versus T2 tumors) or when MRI is contraindicated. Grade of recommendation: Strong recommendation based on moderate-quality evidence, 1B. Magnetic resonance imaging staging of rectal cancer, using standardized technical protocols and reporting templates, assesses the depth of tumor penetration, presence of locoregional nodal metastases, and the relationship between lesions (tumor and/or nodes) within the mesorectum and the mesorectal fascia.46,47 Thus, MRI can help predict surgical clearance of the circumferential resection margin (CRM), the shortest distance between disease (tumor and/or malignant nodes) and the mesorectal fascia.47–49 A positive CRM has been variably defined as cancer within 1 mm or within 2 mm50,51 of the mesorectal fascia or levator ani muscle; the National Comprehensive Cancer Network currently defines it as within 1 mm.52 A positive CRM is associated with increased risk for local recurrence and decreased survival (5-year local recurrence: HR = 3.50; 95% CI, 1.53–8.00; p < 0.05; 5-year overall survival: HR = 1.97; 95% CI, 1.27–3.04; p < 0.01).53–55 Primary tumor features including T4 status, extramural vascular invasion, CRM within 1 mm, or extramural tumor depth of at least 5 mm are considered high-risk features.56,57 These factors should be considered as a critical part of clinical staging and are vital for planning preoperative therapy as discussed in Multidisciplinary Treatment Planning. Endorectal ultrasound should typically be considered complementary to MRI for purposes of clinical staging and is most useful in differentiating between early T stages (ie, T1 versus T2 tumors).57 Magnetic resonance imaging may also be contraindicated when certain implantable medical devices are present (ie, metallic implants, MR incompatible pacemakers).58,59 Disadvantages of EUS include operator dependency, limited accuracy in assessing bulky or locally advanced lesions, patient discomfort, and inability to evaluate stenotic lesions that preclude passage of the transducer.58,59 Accurately staging potentially involved pelvic lymph nodes (including mesorectal, lateral pelvic, and inguinal compartments) remains a diagnostic challenge for all imaging modalities.60 Sensitivity and specificity for clinical nodal staging have been reported as 55% and 74% for CT, 67% and 78% for EUS, and 66% and 76% for MRI.48,61 Nodal staging accuracy may be improved by incorporating criteria such as a spiculated border and mixed signal intensity as seen on MRI.57,62,63 3. Clinical staging for metastatic disease should typically be conducted in patients with rectal cancer. Grade of recommendation: Strong recommendation based on moderate-quality evidence, 1B. Clinical staging of distant metastatic disease should typically be completed before initiating treatment, because the presence of metastatic disease influences the treatment plan. In patients with metastatic rectal cancer from the Swedish Cancer Registry, the most common sites of metastasis were liver (70%), lung (47%), bone (12%), and nervous system (8%).64 Clinical staging should typically include contrast-enhanced CT scan of the chest, abdomen, and pelvis. Pulmonary CT, with its increased sensitivity and better ability to arbitrate otherwise indeterminate lesions over time, is recommended rather than chest x-ray.65,66 Computed tomography without intravenous contrast followed by triphasic (arterial, venous, and portal) contrast is generally the modality of choice for detecting and characterizing hepatic lesions.67–69 For smaller lesions, and to evaluate a liver with background fatty liver changes, MRI may be superior to multidetector CT and positron emission tomography (PET). There is insufficient evidence to support the routine use of PET/CT alone in the clinical staging of primary rectal cancer.60 Although PET/CT has been used for staging patients with suspected disease recurrence or for excluding other sites of distant disease in patients with stage IV rectal cancer being considered for curative-intent surgery, the evidence supporting added clinical value is limited.70,71 Positron emission tomography /CT may have a role in evaluating equivocal findings on contrast-enhanced CT.72,73 4. Restaging evaluation should be considered after neoadjuvant therapy in patients with locally advanced rectal cancer. Grade of recommendation: Strong recommendation based on low-quality evidence, 1C. Restaging evaluation consisting of clinical and endoscopic assessment and cross-sectional imaging should typically be considered after neoadjuvant therapy, in particular, if the assessment of local tumor response would influence the need for additional therapy and/or alter the surgical approach, or if there is a unique concern for interval development of metastatic disease. Importantly, restaging evaluates patients for a possible clinical complete response (cCR) and can adjust patient expectations. Some studies have demonstrated a change in treatment strategy after restaging in 11% to 15% of patients, typically due to identification of metastatic disease, but others have shown limited or no benefit to restaging.74,75 Although restaging is typically performed by repeating the same imaging studies that were done initially, the assessment of tumor response to neoadjuvant therapy has been challenging because of limited T and N staging accuracy for MRI, CT, or EUS in this setting.76–79 Advanced functional MRI (ie, diffusion-weighted MRI) and/or PET/CT scan may potentially improve the accuracy of assessing treatment response.70,80 Multidisciplinary Treatment Planning 1. The treatment of patients with rectal cancer should typically incorporate a multidisciplinary team tumor board discussion. Grade of recommendation: Strong recommendation based on low-quality evidence, 1C. Optimal management of patients with rectal cancer requires input and coordination among a team of clinicians including expertise from surgery, pathology, radiology, radiation, and medical oncology, and other ancillary team members. Although discussion of rectal cancer management by an multidisciplinary team can improve preoperative clinical staging, modify and multimodality treatment, plan technical of surgery, and pathologic staging, more studies are needed to a on and overall survival 2. If a or is being preoperative and should typically be Grade of recommendation: Strong recommendation based on moderate-quality evidence, 1B. with an is typically recommended for patients rectal cancer treatment may and patient can improve time to and Guidelines on and surgery have been previously and Operative 1. excision is an appropriate treatment modality for selected patients with rectal cancer without high-risk Grade of recommendation: Strong recommendation based on moderate-quality evidence, 1B. excision is an curative-intent treatment in selected patients with rectal cancer with clinical and histological excision may also be appropriate for patients with more advanced disease but who are considered for cancer surgery. local excision offers of operative risk and functional it does not or stage the mesorectal lymph The risk of nodal metastasis from T1 lesions from to 11% with risk associated with pathologic features such as invasion, tumor and or preoperative staging and patient are essential when local early depth of invasion (ie, may be difficult with MRI, and EUS may be as a complementary staging in certain Clinical criteria for local excision typically include limited to of the rectal that are well or without invasion, invasion, tumor on and no clinical nodal and that are for full-thickness Given of the of local the grade of this statement has been from a in the 2013 guidelines to a local excision involves full-thickness ideally with a mm circumferential margin with a depth to a of a The surgeon should typically the to facilitate pathologic and or excision should be if The procedure can be performed as a transanal excision or by using a transanal endoscopic platform like transanal endoscopic or transanal invasive surgery there is a of trials, studies that offers better and to more proximal lesions than transanal and and to be Endoscopic an advanced can potentially treat lesions with invasion, but the optimal patient criteria for this The of local recurrence local excision from to for T1 lesions and is than that after Patients should that if pathologic examination risk factors like T invasion, tumor or or invasion, resection will typically be In general, local excision is considered an treatment for lesions because the local recurrence from to and these have an risk for harboring nodal resection should typically be recommended these circumstances. When patients with high-risk T1 and T2 lesions resection or sphincter in combination with local excision has been considered. In a systematic of patients with rectal lesions by local who on to receive = were compared to who resection = the limited retrospective and the local recurrence for and resection were CI, versus CI, for lesions and 15% CI, versus CI, for Thus, in high-risk patients who or are for should typically be recommended after local excision and should be followed by surveillance for a potentially excision has also been performed after neoadjuvant for This has been in clinical assigned and patients with rectal cancer to neoadjuvant and local excision versus reported no in local recurrence or However, a demonstrated high of in particular, pain and for These patients regarding possible long-term and the and of this in routine clinical 1. A thorough surgical should typically be performed at the time of Grade of recommendation: Strong recommendation based on low-quality evidence, 1C. should typically include a thorough assessment of the peritoneal and the to detect or metastatic disease radiographically more advanced local disease to adjacent synchronous lesions, or findings that the operative plan and the to with the be before the vascular and to a 2. For curative resection of of the upper third of the rectum, a mesorectal excision should typically be performed as part of a resection with the mesorectum at least 5 cm the distal margin of the For of the and lower of the rectum, total mesorectal excision should typically be performed as a part of an resection or resection A distal margin is usually adequate for distal rectal cancers when combined with A distal margin is generally for cancers at or the mesorectal Grade of recommendation: Strong recommendation based on the high-quality evidence, surgical is to and and should the and anatomic of a between the and of the fascia of the rectal cancer and associated and tumor excision can the and intraoperative and the of local patients in Research and the local recurrence was for the group with a (ie, of compared with for the group with a (ie, of = Importantly, distal mesorectal of rectal cancer further than distal Although distal is beyond 1 cm from the distal of the cancer in only to of rectal deposits of distal mesorectal nodal can to 3 to cm distal to the primary address the for both and mesorectal for of the upper rectum, the mesorectal excision should typically 5 cm the distal of the for of the and lower rectum, a (ie, excision of all mesorectum to its most distal is required with a distal rectal resection margin at least 2 For of the distal rectum at or the mesorectal a margin of 1 cm in conjunction with a in selected distal margins may be in selected patients who are for sphincter preservation and who have demonstrated tumor regression after neoadjuvant In cases where preoperative anal function and distal pathologic clearance are may be followed by of an colorectal or In cases where the tumor involves the anal sphincter or the levator where

See Article on Page 231-237 The Korean Clinical Practice Guideline for Colon and Rectal Cancer v.1.0 (2012) recommends preoperative chemoradiation as an initial treatment for patients with clinical stage II and III (cT3+ or cN+) rectal cancer [1]. The National Comprehensive Cancer Network guideline v.4. (2013) for rectal cancer also recommends preoperative chemoradiation as an initial treatment for T3N0 or TanyN1-2 rectal cancer. Preoperative chemoradiotherapy significantly decreases the local recurrence rate after a total mesorectal excision (TME) curative resection for rectal cancer, but the functional disability of the anal sphincter after radiation therapy cannot be neglected. In Japan, a major trend in the treatment of rectal cancer has been the radical low anterior resection including lateral node dissection without adjuvant radiotherapy. The Study Group of the Japanese Society for Cancer of the Colon and Rectum reported on the Clinical Significance of the Mesorectal Extension of Rectal Cancer that the distance of mesorectal extension (DME), which was measured with histology after fixation in 20% formalin, was a significant prognostic factor for recurrence-free survival (cut off point, 4 mm) [2]. The multivariate Cox regression analysis showed that the recurrence-free five-year survival rate was significantly higher in patients with a DME ≤4 mm than in patients with DME >4 mm in stage IIA and IIIA cancer, but not in stage IIIC cancer (P = 0.00015, P = 0.0001, and P = 0.2697, respectively). The reports suggested that local recurrences were increased by the status of cancer-positive lymph nodes even in the same category of T3 cancer in patients without radiation therapy. The distal resection margin (DRM) means the length of the tumor-free normal mucosa and rectal wall. Han et al. [3] published the manuscript, 'Association between a close distal resection margin and recurrence after sphincter-saving resections for T3 midor low-rectal cancer without radiotherapy.' With retrospective data, they described the 5-year local recurrence rates as 6.69% in patient with DRM ≤10 mm and 9.52% in patients with DRM >10 mm, respectively (DRM cut off point, 1 cm; P = 0.3981). However, they gave no descriptions of cancer-positive lymph nodes in the groups with stage IIA, IIIB, and IIIC cancer. The local recurrence may be influenced not only by DRM but also by the status of lymph nodes. A Norwegian national study recommended a DRM of >10 mm for rectal cancer patients treated without radiotherapy [4]. The 5-year local recurrence rate was 14.5% for patients with DRM of 0-10 mm compared to 8.66% for patients with DRM >11 mm (P < 0.001). The proportions of T3 cancer were 48% and 63%, respectively, in those two groups. Current Japanese guidelines state a 2-cm DRM is needed for rectal cancer with a distal edge below the peritoneal reflection. Intramural and extramural distal spread prevents local control and promotes systemic metastasis. If the specimen is not pinned, the length of the DRM can shrink by 50% in a nonradiated rectum after formalin fixation. A gross determination of a safe distal resection margin is difficult in the operating room. The frozen-section result for the DRM may be falsely negative in 12% of all cases. A systemic review supported the practice of sphincter preservation in selected settings of close distal resection margins (≤1 cm) after mesorectal excision for distal rectal cancer [5]. A further subgroup study suggested that margins as close as ≤5 mm, if they were indeed negative, might be acceptable. However, the importance of patient and tumor selection for this approach must be emphasized. In distal rectal cancer, the mesorectal fascia does not extend beyond the puborectalis level, and the anal sphincter is another barrier for safe distal resection margins. Local recurrence may develop with uninvolved margins related to lymphatic spread from the DRM. In preoperative radiation cases, a distal clearance margin of 1 cm or less may a safe distance in patients who undergo lower rectum cancer surgery [6]. We would like to conclude with the following remark. Although reduction of the DRM to less than 10 mm does not increase local recurrences in many low-risk patients, a DRM >10 mm is safe in cases of rectal cancer with lymphovascular invasion, perineural invasion and multiple lymph-node metastases.

Report overall long-term results of stage 0 rectal cancer following neoadjuvant chemoradiation and compare long-term results between operative and nonoperative treatment. Two-hundred sixty-five patients with distal rectal adenocarcinoma considered resectable were treated by neoadjuvant chemoradiation (CRT) with 5-FU, Leucovorin and 5040 cGy. Patients with incomplete clinical response were referred to radical surgical resection. Patients with incomplete clinical response treated by surgery resulting in stage p0 were compared to patients with complete clinical response treated by nonoperative treatment. Statistical analysis was performed using chi2, Student t test and Kaplan-Meier curves. Overall and disease-free 10-year survival rates were 97.7% and 84%. In 71 patients (26.8%) complete clinical response was observed following CRT (Observation group). Twenty-two patients (8.3%) showed incomplete clinical response and pT0N0M0 resected specimens (Resection group). There were no differences between patient's demographics and tumor's characteristics between groups. In the Resection group, 9 definitive colostomies and 7 diverting temporary ileostomies were performed. Mean follow-up was 57.3 months in Observation Group and 48 months in Resection Group. There were 3 systemic recurrences in each group and 2 endorectal recurrences in Observation Group. Two patients in the Resection group died of the disease. Five-year overall and disease-free survival rates were 88% and 83%, respectively, in Resection Group and 100% and 92% in Observation Group. Stage 0 rectal cancer disease is associated with excellent long-term results irrespective of treatment strategy. Surgical resection may not lead to improved outcome in this situation and may be associated with high rates of temporary or definitive stoma construction and unnecessary morbidity and mortality rates.

To analyze early results of a single institution's experience using neo-adjuvant chemoradiotherapy in locally advanced, ultrasound-staged rectal cancer. Since 1998, 67 consecutive patients (36 males and 31 females; mean age, 59.5) have received preoperative combined treatment for T3 or T4 rectal cancer. All patients were staged by endorectal ultrasound and computed tomography, and all had a pathology-demonstrated invasive adenocarcinoma of the rectum. Patients were treated preoperatively with concomitant radiochemotherapy: pelvic irradiation (50 Gy in 25 fractions) and protracted-venous-infusion 5-fluorouracil (225 mg/m2/d, 7 days per week). Patients were restaged within 4 weeks, then submitted to surgery within 6-7 weeks after the end of therapy. Adjuvant postoperative chemotherapy with 5-fluorouracil plus folinic acid--the "de Gramont" schedule--for 24 weeks was purposed to all patients. Radiotherapy was completed in all cases; only one patient required suspension of the treatment for grade 4 toxicity (diarrhea). Instead, chemotherapy was interrupted in 3 cases (2 for central venous catheter thrombosis and 1 for grade IV diarrhea). Sixty-six patients underwent surgical resection (1 patient died before surgical treatment). Radical surgery was performed in 94%, and 46% of the 26 patients with distal rectal cancer had a conservative sphincter-sparing surgery. A complete pathologic response (defined as no evidence of viable tumor cells) was obtained in 22%. At a median follow-up of 17 months, distant metastases have been observed in 10 patients, and 3 of them developed a local recurrence. The actuarial estimations of 4-year overall survival, disease-free survival, local and distant control are 79%, 61%, 94% and 61%, respectively. Preoperative chemoradiotherapy seems to be an effective and well-tolerated treatment with a low complication rate. The high percentage of down-staging and sphincter sparing, also in distal rectal cancer, shows the efficacy of the treatment, which could significantly influence the incidence of relapses and quality of life.

Local excision (LE) has been proposed as an alternative to radical resection for early distal rectal cancer, for which the optimal oncologic treatment remains unclear. The goal of this study was to compare the overall survival of rectal cancer patients with early distal tumors who underwent LE versus abdominoperineal resection (APR) using a large contemporary database. The National Cancer Database (2004-2013) was used to identify patients with early T-stage rectal adenocarcinoma who underwent LE or APR. Patients were split into groups based on T stage and type of surgery (LE vs. APR). The primary outcome measure was overall survival. An adjusted Cox proportional hazards model was used to evaluate the impact of treatment strategy on survival. Overall, there were 2084 patients with T1 tumors and 912 patients with T2 tumors. For patients with T1 disease, after adjusting for age, sex, income level, race, Charlson score, insurance payor, and tumor size, there was no significant difference in survival between the LE and APR groups (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.65-1.22; P = 0.49). For patients with T2 disease, after adjusting for age, Charlson score, and tumor size, there was no significant difference in survival between patients undergoing LE + chemoradiation therapy (CRT) and APR (HR 1.11, 95% CI 0.84-1.45; P = 0.47). Patients with early distal rectal adenocarcinoma who underwent LE had similar survival to patients who underwent APR. LE is an acceptable oncologic treatment strategy for patients with T1 rectal cancers, and LE with CRT is an acceptable oncologic treatment for patients with T2 distal rectal cancers.