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• W2657185887 abstract "A definition of rectal cancer is important for optimal planning of neoadjuvant therapy and surgical strategy. Anatomically the rectum is distal to the sigmoid colon and its upper limit is the termination of the sigmoid mesocolon. A commonly used definition is an adenocarcinoma with a distal margin at or below 15 cm from the anal verge, measured by rigid sigmoidoscopy. Standard anatomical texts put this at the level of the third sacral vertebra (Williams & Warwick, 1980) but it is generally agreed by surgeons that the rectum starts at the sacral promontory (UKCCCR, 1989). Whilst there remains debate about the proximal limit of the rectum, there is increasing recognition of the complexity of management of low rectal cancers. The Low Rectal Cancer Development Program (LOREC) has defined a ‘low’ rectal cancer as an MRI-based anatomical definition of an adenocarcinoma with its lower edge, at or below the origin of the levators at the pelvic side-wall. This usually corresponds to a measurement of within 6 cm of the anal verge (PELICAN Cancer Foundation; Salerno et al., 2006a, 2006b). A low rectal cancer should be defined as an MRI-based anatomical definition of an adenocarcinoma with its lower edge, at or below the origin of the levators at the pelvic side-wall. This usually corresponds to a measurement of within 6 cm of the anal verge. Recommendation grade D The Clinical Guidelines published by NICE (CG 131) in November 2011 defined three broad categories of rectal cancer, relating to the risk of pelvic local recurrence (LR) following treatment (Table 1) and represent a useful starting point for considering treatment strategy (National Institute for Health and Clinical Excellence, 2011). The increasingly widespread use of total mesorectal excision (TME), involving meticulous dissection of the mesorectal fascia (MRF) (Heald et al., 1982) has had a major impact in reducing LR of rectal cancer. The ‘low’ and ‘moderate’ LR groups can be considered as ‘resectable’ or ‘operable’, because the surgical MRF resection margin is not threatened. The ‘high’ LR risk group is at significant risk of surgical MRF resection margin being involved, unless some form of tumour downstaging can be achieved preoperatively. In addition, both the ‘moderate’ and the ‘high’ LR risk groups are at significant risk of developing distant metastatic disease, which is the main cause of death. These considerations drive the current treatment and clinical research strategies described below (Table 4.1). cT1 or cT2 or cT3a and no lymph node involvement any cT3b or greater, in which the potential surgical margin is not threatened or any suspicious lymph node not threatening the surgical resection margin or the presence of extramural vascular invasion a threatened (<1 mm) or breached resection margin or low tumours encroaching onto the inter-sphincteric plane or with levator involvement An involved circumferential resection margin (CRM), defined as tumour ≤1 mm from the surgical resection margin is an important, independent predictor of LR (historically up to 85%) (Nagtegaal et al., 2002; Quirke et al., 1986), distant metastases (DM) (Mawdsley et al., 2005) and poorer overall survival (OS) (Wibe et al., 2002), even after TME (Marijnen et al., 2003). The CRM can be involved by direct or discontinuous tumour spread, lymph node spread, lymphovascular spread and perineural spread (Nagtegaal & Quirke, 2008). The risk of CRM involvement is also related to the quality of TME surgery (Nagtegaal et al., 2002; Quirke et al., 2009). Local recurrence can also occur despite a clear CRM, possibly from lymphatic spread to pelvic side-wall nodes (Ueno et al., 2007). In patients undergoing surgery, with or without preoperative radiotherapy (RT), the combination of CRM and lymph node status may be a more effective discriminator of prognosis than TNM staging (Nagtegaal et al., 2007). Magnetic resonance imaging (MRI) is the current gold standard imaging modality for pre-treatment assessment of CRM involvement (MERCURY Study Group, 2006; The Royal College of Radiologists, 2014). High resolution MRI is essential for optimal staging and to guide management decisions (Al-Sukhni et al., 2012; Battersby et al., 2015). A well-performed MRI can identify the extent of extramural spread (T3a-d), which has a greater predictive value for nodal involvement than assessment of lymph node size per se. Lymph node status remains difficult to assess pre-treatment with poor sensitivity and specificity, although sensitivity may be increased by the addition of diffusion weighted MRI sequences (Heijnen et al., 2013). Assessment of extramural vascular invasion (EMVI) by MRI may define a subgroup at high risk of local and distant recurrence (Al-Sukhni et al., 2012; Battersby et al., 2015; Chand et al., 2015). This has been highlighted by the MERCURY study; independent MRI-defined risk factors were EMVI, tumours <4.0 cm from the anal verge and anterior tumours. A systematic review and meta-analysis (Al-Sukhni et al., 2012) concluded that MRI specificity was significantly higher for prediction of CRM involvement (94%, 95% CI 88–97) than for T (75%, 95% CI 68–80) and N stage (71%, 95% CI 59–81). Standardized proforma based reporting (Taylor et al., 2010) may improve staging consistency nationally and increase minimum dataset collection to 100% as shown in the Royal College of Radiologists/NCIN CASPAR project (Tait, 2015). All patients with rectal cancer being considered for curative surgery should have locoregional staging by high resolution MRI pelvis, unless there are contraindications. Recommendation grade B MRI should be reported as per Royal College of Radiologists’ guidance [BFCR(14)2]. Proforma based reporting can standardize and improve completeness of minimum staging data. Recommendation grade C Staging investigations should be reviewed by the Colorectal MDT in the context of the patients’ clinical history and findings, histology and results of other investigations to decide on the subsequent management of the patient. Recommendation grade D Colorectal MDTs should correlate pre-treatment radiological staging with post-surgical pathological stage. Recommendation grade D Radiotherapy and chemotherapy for rectal cancer should only be given after discussion and agreement by the Colorectal MDT, within facilities conforming to national guidelines. Recommendation grade C Introduction of population-based bowel screening, combined with improved access to diagnostic services has resulted in a downward shift in rectal cancer stage at presentation. The term early rectal cancer (ERC) encompasses a set of macroscopic and microscopic features that characterize tumours with an excellent prognosis following standard surgery. Such tumours may also be amenable to local techniques that aim to preserve the rectum and reduce treatment-related morbidity. Optimal management of ERC is yet to be determined; in fact there is no consensus as to the definition of ERC. A recent EAES/ESCP consensus conference stated that ‘ERC is a rectal cancer with good prognostic features that might be safely removed preserving the rectum, and that will have a very limited risk of relapse after local excision’ (Morino et al., 2015). ‘Conservative’ definitions such as this limit the application of rectal sparing treatment, whereas broader definitions increase the likelihood of under-treating patients. New multimodal treatment strategies may allow safe expansion of the application of rectal preserving therapy, while stratification through molecular profiling may personalize care and reduce risk of under-treatment. Rectal neoplasms present as a spectrum, ranging from benign to malignant. The ‘Significant Polyp Early Colorectal Cancer’ (SPECC) programme, supported by ACPGBI aims to improve outcomes by reducing over treatment of benign lesions and under treatment of cancer. A significant rectal neoplasm is defined as a sessile polyp >20 mm in diameter, which is morphologically aberrant, where polypectomy may be unsafe or result in incomplete excision (Moran & Dattani, 2016). Explain to patients and their family members or carers (as appropriate) that due to insufficient good quality clinical evidence, the optimal treatment for early rectal cancer is uncertain. Recommendation grade D Offer patients with early rectal cancer the opportunity to participate in clinical trials (if eligible) that evaluate the treatment options for early rectal cancer. Recommendation grade D There are particular pitfalls associated with the evaluation of rectal SPECC lesions and it is important that MDT's demonstrate appropriate expertise in the clinical, radiological and histopathological assessment of these cases. Evaluation should optimally include: An MRI performed prior to local excision of all rectal SPECC lesions is recommended. A significant proportion (20–40%) of SPECC lesions with ‘benign’ histology on initial biopsy are subsequently found to contain cancer within the lesion on complete lesion excision, and interpretation of MRI performed immediately after full thickness local excision is often hampered by surgical artefact and the presence of reactive lymph nodes. A pre-treatment MRI also serves as an important reference, for comparison with follow up imaging, to enable early detection of luminal or lymph node recurrence. In summary, the assessment, decision-making and treatment of rectal SPECC lesions are complex and continue to evolve. Expertise in imaging, pathology and surgery are essential to deliver a safe and effective ERC service and concentration of specialist services will facilitate this. For these reasons, NICE (CG 131) recommended formation of early rectal cancer MDTs. Patients with significant rectal neoplasms (SPECC lesions) should be adequately assessed prior to any definitive treatment. Recommendation grade C Patients with significant rectal neoplasms (SPECC lesions), which may be suitable for rectal preserving treatment, should have access to an early rectal cancer MDT for further assessment and management. Recommendation grade D A pT1 malignant rectal polyp is an adenocarcinoma arising within a pre-existing adenoma in which tumour cells have breached the muscularis mucosa, extending into the submucosa but not the muscularis propria (Williams et al., 2013). This is often an unexpected finding following snare polypectomy or endoscopic mucosal resection on lesions presumed to be benign. Almost all locally removed malignant rectal polyps are stage I cancers and generally associated with an excellent prognosis. With no further treatment, the risks are of luminal recurrence and progression of involved undetected mesorectal lymph nodes. Current guidelines consider carcinoma within 1 mm of the resection margin as being involved but recent evidence suggests that the risk of recurrence is highest only when tumour is present at the resection margin or within diathermized tissue (Brown et al., 2016). Risk factors for lymph node involvement include extent of submucosal invasion, intramural lymphovascular invasion (LVI) and poor differentiation. However, these features are often difficult to assess due to destruction of important anatomical landmarks by the tumour and surgical factors such as piecemeal resection and diathermy artefact. Evidence of complete macroscopic removal by endoscopic assessment is important as pathological assessment of piecemeal specimens may be equivocal. Patients found to have pT1 rectal cancer polyps following local excision should be routinely staged with pelvic MRI, unless this was performed prior to the procedure. Staging for distant metastases by CT should be routinely performed as for all colorectal cancers. Piecemeal resection of significant rectal neoplasms (SPECC lesions) should be avoided, as this can preclude comment on the completeness of excision and complicates assessment of prognostic features. Recommendation grade C Standard primary radical TME is an oncologically effective treatment for early stage rectal cancer; only 2% and 12% of patients experience local or distant failure respectively (Peeters et al., 2007). However, radical resection of a rectal tumour requires a permanent stoma in approximately 25% of cases while many more patients have a temporary stoma, many of which are not reversed (Healthcare Quality Improvement Partnership, 2015). Six-month mortality following radical curative surgery for rectal cancer is 4.6% for patients aged 65–74 years rising to 13.4% for patients aged 75–84 years (Kapiteijn et al., 2001; Rutten et al., 2008). Recognized long-term morbidities of radical TME include impaired anal sphincter function, pelvic nerve damage (male and female urinary and sexual dysfunction) and small bowel adhesion formation. Early rectal tumours may be locally excised through the anus with low morbidity and mortality using Transanal Endoscopic Microsurgery (TEM) (Bach et al., 2009; Cataldo et al., 2005) allowing for preservation of the rectum and its function. Full thickness excision offers accurate pathological assessment and potential cure for many pT1 and pT2 cancers. Morbidity and mortality after local excision are lower than after radical resection, with a reported 30-day mortality of 0.5% compared with 2.4% in a study of 5305 patients (You et al., 2007). However, several case series have reported LR rates ranging from 5% to 28% for pT1 cancers and 11% to 45% for pT2 cancers following transanal excision (Endreseth et al., 2005; Garcia-Aguilar et al., 2000). These series predate accurate pre-treatment MRI staging, which may identify and exclude a proportion of high-risk patients. These series also predate widespread adoption of ‘optimized’ endoscopically-assisted TEM or transanal minimally invasive surgery (TAMIS) and include patients treated using per-anal excision. Per-anal excision is associated with higher recurrence rates, whilst endoscopically-assisted techniques are broadly similar in efficacy (Barendse et al., 2012; Moore et al., 2008). Presence of untreated involved mesorectal lymph nodes is another cause of local disease failure following local excision. The risk of lymph node involvement increases with depth of bowel wall penetration; for pT1 tumours the risk ranges from 1% to 3% for Kikuchi sm1, 8% for sm2 and 23% for sm3 (Tytherleigh et al., 2008). Overall incidence of lymph node metastasis ranges from 6% to 14% for pT1 tumours, 17% to 23% for pT2 tumours, and 49% to 66% for pT3 tumours (Ricciardi et al., 2006). Tumour implantation is another potential source of luminal recurrence and may explain why LR rates are often higher following local excision, than implied by the risk of lymph node metastasis. Prospectively collected data from the UK ACPGBI TEM Collaboration (n = 424) (Bach et al., 2009) (Table 4.2) identified depth of invasion, maximum tumour diameter and the presence of LVI as independent predictors for LR. The lowest LR rate of <5% was seen in well or moderately differentiated pT1 sm1 lesions, without intramural LVI, measuring <3 cm. However, the majority of pT1-2N0 rectal cancers had one or more of the identified risk factors, with significantly higher LR rates of 15–30% following TEM alone. The risk of LR following local excision has to be considered within the context of alternative treatment by radical surgery and its morbidity and mortality risks. For most patients, a risk of LR <10% is acceptable but many will accept a risk of 30% to avoid the consequences of radical surgery (Johnston et al., 2013). Patient co-morbidity and life expectancy are important considerations in decision-making and there is no clear answer, although data are emerging on the efficacy of multimodal treatment of frail patients with ERC (Smart et al., 2016). Decisions need to be tailored to individual patients, although clinicians should leave patients in no doubt what is the standard of care for this stage of disease, offering the optimum chance of cure. The Association of Coloproctology of Great Britain and Ireland introduced guidance for the use of local excision for ERC (Williams et al., 2013). These include: When these criteria are adhered to, lymph-node involvement and LR rates of less that 10% can be expected in this population. For similar stage of cancer, radical surgery is associated with mortality in 3–5%, major morbidity in 20–40% and likelihood of stoma of 40% (Marijnen et al., 2005). The impact of radical surgery for early stage disease on long-term quality of life is well established (Doornebosch et al., 2007). This introduces the concept of trade-off in ERC where improved functional outcome and quality of life are traded off against potentially poorer oncological outcome. It can be a complex model for decision-making in ERC management, balancing optimal oncological treatment with patient wishes to minimize the adverse effects of treatment. Local excision with curative intent should be offered through endoscopic means (TEM, TEO, TAMIS) in preference to traditional per-anal excision. Recommendation grade C Local full thickness excision with negative margins of pT1 sm1 tumours (well or moderately differentiated) leads to very low local recurrence rates and may be considered standard of care. Recommendation grade C Following local excision pathology review, patients deemed be at an unacceptably high risk of LR should be considered for completion radical surgery. This approach is believed to offer good oncological outcomes (Bach et al., 2009; Hahnloser et al., 2005) and is quite different to salvage surgery for recurrent disease, where more extensive multimodality treatment may be necessary. Surgical outcomes are similar to radical surgery performed as the first procedure in terms of morbidity, mortality and length of hospital stay (Hompes et al., 2013). Anecdotally it is often technically more difficult that primary TME and permanent stoma rates may be higher compared to use of TME as primary treatment (van Gijn et al., 2013). There is no consensus on timing of completion surgery after local excision, which can vary from a few weeks to several months. Complications of local excision, such as wound dehiscence cause inflammation of the mesorectum and adherence of the mesorectal fascia to the pelvic side-wall. Postoperative radiotherapy may be considered for ‘high-risk’ patients who are unable or unwilling to undergo TME surgery. However, the benefit of adjuvant radiotherapy in reducing recurrence risk following local excision remains unproven (Greenberg et al., 2008; Rackley et al., 2016) and requires further high quality prospective research. In view of the increased risk of LR following local excision alone, patients must be offered regular surveillance to facilitate detection of recurrent disease at the earliest opportunity, in order to maximize the success of radical salvage surgery. Early detection can mitigate the impact of LR (De Graaf et al., 2009). Although the optimal surveillance strategy remains undefined, endoscopic assessment at 3–6 monthly intervals coupled with MRI pelvis at 3–6 monthly intervals and CT to detect distant metastases at 12 monthly intervals for 3–5 years is generally used. After local excision, patients with unfavourable pathology should be offered completion surgery with anterior resection or abdominoperineal resection. Every effort should be made to minimize the number of patients treated in this way, by placing emphasis on pre-treatment assessment by expert MDTs. Recommendation grade C After local excision alone, patients should be followed up under a defined surveillance protocol to detect recurrent disease at the earliest stage possible. Current recommendations are 3–6 monthly MRI, CEA and flexible sigmoidoscopy. Recommendation grade C Maas et al. 2010 reviewed 2323 patients treated with CRT demonstrating a clear correlation between the clinical T-stage and the pCR rate (cT1: 58%, cT2: 28%, cT3: 16% and cT4: 12%). The success rate of an organ preserving approach that incorporates radiotherapy will be dependent on the tumour stages treated. Combining radiotherapy with TEM surgery may: (a) remove minimal residual primary tumour, (b) effectively treat microscopic mesorectal lymph node metastases, (c) facilitate local excision with clear margins and (d) reduce the likelihood of tumour implantation at surgery. However, limited prospective evidence exists to guide the use of radiotherapy and local excision as curative treatment for ERC. The ACOSOG Z6041 (Garcia-Aguilar et al., 2012) and CARTS (Verseveld et al., 2015) trials investigated the safety and effectiveness of CRT and transanal excision for treatment of ERC. In addition, Appelt et al., (Appelt et al., 2015) studied the effectiveness of CRT combined with brachytherapy. Each of these studies reported high rates of organ preservation combined with low rates of LR, but all observed marked treatment-related toxicities that negated any benefit. A retrospective analysis of a cohort of UK patients (n = 62) with ERC, who were predominantly unfit for TME, treated with short course radiotherapy (SCRT) 25 Gy in 5 fractions and TEM reported high pCR rates (32%), low recurrence rates and low toxicity (Smart et al., 2016). The TREC trial evaluated the feasibility of randomizing fit patients with ERC between standard TME and rectal preservation using SCRT followed by TEM, is due to report results shortly. The international STAR-TREC trial will randomize patients with ERC into one of three arms; (a) standard surgery, (b) rectal preservation with mesorectal CRT and selective transanal excision or (c) rectal preservation with mesorectal SCRT and selective transanal excision. This study aims to recruit over 400 patients in the UK, Netherlands and Denmark to determine if TME surgery results in demonstrably lower pelvic relapse rates than the rectal sparing techniques. In summary, multimodal treatment of ERC using CRT combined with either TEMS or brachytherapy has resulted in unacceptable toxicities, defeating the concept of rectal sparing surgery. These treatments may be taken forward in clinical studies such as STAR-TREC, which will introduce new mesorectal irradiation techniques for ERC, designed to reduce treatment related toxicities. The application of radiotherapy in ERC remains the subject of clinical trials. Local excision after SCRT or CRT may be considered in patients with early rectal cancer who are unfit or refuse standard resectional surgery and appear to have residual disease. The role of preoperative radiotherapy and local excision in patients with early rectal cancer, who are fit for TME remains the subject of clinical trials. Recommendation grade C An alternative strategy for treating ERC is with 50 KV contact x-ray brachytherapy (CXB), also known as the Papillon technique, on small lesions (<3 cm), either alone (cT1 tumours) or combined with a course of pelvic external beam radiotherapy (EBRT) for cT2 tumours or cT1-2 tumours >3 cm (Hershman et al., 2003). Several studies have reported promisingly low LR rates (Sun Myint et al., 2007). Since introduction of CXB to the UK in 1993 (Sun Myint, 2007), although its use remains limited, several UK centres are being equipped with a new generation of CXB machines (Gerard et al., 2011). NICE (IPG 532) has recommended that in patients for whom surgery is not considered suitable, current evidence on the efficacy and safety of CXB for early-stage rectal cancer is adequate to support its use. However in patients who are considered suitable for surgery, but choose not to have an operation, although the evidence on the safety of CXB is adequate, the evidence on efficacy is inadequate (National Institute for Health and Clinical Excellence, 2015b). Patient selection to undergo CXB should be through a colorectal MDT, which includes a clinical oncologist and a colorectal surgeon with expertise in local excision techniques. Patients should be informed of all available different treatment options to enable shared decision making before proceeding with treatment. Data on patients undergoing CXB should be submitted to a NICE-supported audit database, based at Guildford. There are few randomized trial data on the use of CXB alone in patients with ERC (Lindegaard et al., 2007). One randomized trial evaluating the role of CXB boost following EBRT reported a significant increase in sphincter preservation compared to the no boost group (76% v 44%; P = 0.004), with no difference in morbidity, LR, and 2-year OS (Gerard et al., 2004). A randomized trial (OPERA) evaluating whether a CXB boost improves organ preservation when compared to an EBRT boost, has started to recruit in France and plans are in progress to open this trial in the UK (Gerard et al., 2011). The role of preoperative high dose-rate (HDR) brachytherapy was evaluated by NICE (IPG 531), stating that current evidence on the safety of this treatment for rectal cancer and its efficacy in reducing tumour size appears adequate (National Institute for Health and Clinical Excellence, 2015c) but there is no evidence that it provides additional benefit when used as a boost to EBRT. However, rectal HDR brachytherapy can be offered for bulky residual rectal tumours following EBRT, in patients not suitable for surgery or CXB. Rectal HDR brachytherapy can also be offered for recurrent tumours following surgery or EBRT for symptom control (Hoskin et al., 2004). Contact x-ray brachytherapy (CXB) is considered a treatment option for patients with early rectal cancer as an alternative to TEM, for patients considered not suitable for surgery or for patients considered suitable for surgery, but who decline operation. This should only be offered with the appropriate arrangements in place for clinical governance, consent, audit and research, as recommended by NICE IPG 532. Recommendation grade B Two meta-analyses (Camma et al., 2000; Colorectal Cancer Collaborative Group, 2001), a systematic review (Munro & Bentley, 2002) and a Cochrane review (Wong et al., 2007) of randomized trials comparing the addition of radiotherapy (RT) to standard surgery consistently demonstrate a reduction of LR risk, with both pre- and postoperative RT, reduction of rectal cancer deaths but not improvement of OS. Radiotherapy delivery techniques in the early trials were sub-optimal by today's standards, including use of large parallel-opposed fields, which were associated with increased non-cancer deaths (Colorectal Cancer Collaborative Group, 2001). Preoperative RT to the pelvis can either be delivered by conventional fractionation (long course RT) of 45–50.4 Gy in 25–28 fractions over 5 weeks or by a short course of preoperative RT (SCPRT) of 25 Gy in 5 fractions over 1 week. Long course RT is often used to shrink or ‘downstage’ the tumour prior to surgical resection and can be made more effective by adding synchronous fluropyrimidine-based chemotherapy, also known as chemoradiotherapy (CRT). Surgery is usually performed 6–10 weeks after completion of CRT, to allow time for maximal response to occur. In contrast, SCPRT delivers a lower dose of radiation using larger doses per fraction, over a short duration followed by immediate surgery, which is scheduled for the following week. The short interval between commencing radiotherapy and surgery (usually ≤10 days) does not allow for any significant tumour shrinkage or downstaging. The Swedish Rectal Cancer trial (n = 1168) defined clinical practice in the 1990s (Folkesson et al., 2005; Swedish Rectal Cancer Trial, 1997). It compared the addition of SCPRT prior to surgery with surgery alone and reported fewer LRs and improved 5-year OS with SCPRT. Since then significant advances in the multidisciplinary management of rectal cancer have resulted in a marked reduction of LR after TME alone, with centres reporting LR rates as low as 3–6% (Heald & Ryall, 1986; Martling et al., 2000). This raised the question of whether there remained any benefits for SCPRT in addition to TME. Two trials were designed to address this question: the Dutch Colorectal Cancer Group trial (n = 1861) (Kapiteijn et al., 2001; Peeters et al., 2007) and the UK MRC CR07/NCIC-CTG C016 trial (n = 1350) (Sebag-Montefiore et al., 2009). Patients were randomized between SCPRT followed by immediate surgery or initial surgery followed by selective postoperative RT (Dutch trial) or CRT (CR 07) in patients found to have a CRM ≤1 mm. Unlike the Dutch trial, TME was not a protocol requirement in CR 07 but was performed in 93%. The use of SCPRT halved the risk of LR from 10.9% to 5.6% (P < 0.001) and from 11.5% to 4.7% at 5-years (HR 0.39, P < 0.0001) respectively. There was no difference in OS in both trials, although neither was statistically powered to detect a difference. The commonest cause of death was distant metastatic disease. Although patients found to have an involved CRM following SCPRT and TME remain at significant risk of LR (Marijnen et al., 2003), further radiotherapy given postoperatively is contraindicated. The risk of long-term radiation toxicity associated with this approach is considerable (over 84% at 5-years) (Svoboda et al., 1999). The EORTC 22921 trial (n = 1011) (Bosset et al., 2005; Bosset et al., 2006) and the FFCD 9203 trial (n = 733) (Gerard et al., 2006) compared preoperative long course CRT with long course RT in resectable (cT3-4) mid and low rectal cancers. Patients in EORTC 22921 were randomized to receive adjuvant 5FU in a 2 × 2 trial design, whereas all patients in FFCD 9203 received adjuvant 5FU. TME was not a protocol requirement in either trial. Both trials demonstrated that synchronous 5FU with long course RT significantly reduced LR compared to RT alone (8–9% vs 17%). Compliance with adjuvant 5FU was poor (only 43% received the protocol dose in EORTC 22921). Despite an improvement in pCR rate and reduced LR the addition of c" @default.
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• W2657185887 title "Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) - Multidisciplinary Management" @default.
• W2657185887 cites W141482010 @default.
• W2657185887 cites W1492190372 @default.
• W2657185887 cites W1520173814 @default.
• W2657185887 cites W1583454926 @default.
• W2657185887 cites W1585172067 @default.
• W2657185887 cites W1764231357 @default.
• W2657185887 cites W1775019116 @default.
• W2657185887 cites W1880063947 @default.
• W2657185887 cites W1893228501 @default.
• W2657185887 cites W1899767765 @default.
• W2657185887 cites W1900000927 @default.
• W2657185887 cites W1956561450 @default.
• W2657185887 cites W1964246852 @default.
• W2657185887 cites W1965026575 @default.
• W2657185887 cites W1967126296 @default.
• W2657185887 cites W1967776133 @default.
• W2657185887 cites W1968723620 @default.
• W2657185887 cites W1969561516 @default.
• W2657185887 cites W1971300092 @default.
• W2657185887 cites W1972637879 @default.
• W2657185887 cites W1974902120 @default.
• W2657185887 cites W1978224105 @default.
• W2657185887 cites W1979642977 @default.
• W2657185887 cites W1982185305 @default.
• W2657185887 cites W1983265147 @default.
• W2657185887 cites W1994795369 @default.
• W2657185887 cites W1994943514 @default.
• W2657185887 cites W1997160907 @default.
• W2657185887 cites W2003266266 @default.
• W2657185887 cites W2005750278 @default.
• W2657185887 cites W2005991780 @default.
• W2657185887 cites W2009781085 @default.
• W2657185887 cites W2010401910 @default.
• W2657185887 cites W2010744046 @default.
• W2657185887 cites W2015452694 @default.
• W2657185887 cites W2017132889 @default.
• W2657185887 cites W2020956130 @default.
• W2657185887 cites W2021416608 @default.
• W2657185887 cites W2022047512 @default.
• W2657185887 cites W2023366731 @default.
• W2657185887 cites W2023623711 @default.
• W2657185887 cites W2024391869 @default.
• W2657185887 cites W2025037284 @default.
• W2657185887 cites W2025508929 @default.
• W2657185887 cites W2032825860 @default.
• W2657185887 cites W2033407995 @default.
• W2657185887 cites W2034059743 @default.
• W2657185887 cites W2036704220 @default.
• W2657185887 cites W2038010015 @default.
• W2657185887 cites W2039012840 @default.
• W2657185887 cites W2039925327 @default.
• W2657185887 cites W2039973263 @default.
• W2657185887 cites W2041583693 @default.
• W2657185887 cites W2041727653 @default.
• W2657185887 cites W2043317119 @default.
• W2657185887 cites W2047778994 @default.
• W2657185887 cites W2048580016 @default.
• W2657185887 cites W2052779140 @default.
• W2657185887 cites W2053230335 @default.
• W2657185887 cites W2056520573 @default.
• W2657185887 cites W2058076434 @default.
• W2657185887 cites W2060706863 @default.
• W2657185887 cites W2064327476 @default.
• W2657185887 cites W2064802225 @default.
• W2657185887 cites W2067803433 @default.
• W2657185887 cites W2068701323 @default.
• W2657185887 cites W2069115558 @default.
• W2657185887 cites W2069793735 @default.
• W2657185887 cites W2070349109 @default.
• W2657185887 cites W2071971830 @default.
• W2657185887 cites W2072201955 @default.
• W2657185887 cites W2072729991 @default.
• W2657185887 cites W2072825452 @default.
• W2657185887 cites W2072878374 @default.
• W2657185887 cites W2077582039 @default.
• W2657185887 cites W2079737457 @default.
• W2657185887 cites W2082160016 @default.
• W2657185887 cites W2085867197 @default.
• W2657185887 cites W2087584936 @default.
• W2657185887 cites W2089714928 @default.

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