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• W2155492044 abstract "The incidence of rectal cancer in the European Union is ∼35% of the total colorectal cancer incidence, i.e. 15–25/100 000 per year. The mortality is 4–10/100 000 per year with the lower figures valid for female individuals. The risk increases with age. Median age at diagnosis is about 70 years or slightly older in most European countries. The literature on risk factors for colorectal cancer is extensive. Diet and dietary components are important, although the risk increases are not marked and not universally seen. Dietary fibre most likely decreases the risk, whereas excessive consumption of red or processed meat most likely increases it. Smoking increases the risk as does at least moderate and heavy alcohol use. It has been noted that an otherwise healthy lifestyle can substantially reduce the risk [1.Kirkegaard H. Johnsen N.F. Christensen J. et al.Association of adherence to lifestyle recommendations and risk of colorectal cancer: a prospective Danish cohort study.BMJ. 2010; 341: c5504Crossref PubMed Scopus (140) Google Scholar]. Regular use of NSAIDs is associated with reduced incidence. Diabetes type II increases the risk and there is probably a causal role of hyperinsulinaemia and insulin-like growth factors. Ulcerative colitis and Crohn's disease also increase the risk. Up to about 15% of cases have a hereditary component although this is more pronounced for colon cancer than for rectal cancer. The most common disorders are Lynch syndrome and familial adenomatous polyposis. Diagnosis is based on a digital rectal examination including rigid sigmoidoscopy with biopsy for histopathological examination. Tumours with distal extension to ≤15 cm from the anal margin (as measured by rigid sigmoidoscopy) are classified as rectal, more proximal tumours as colonic. The majority (95%–98%) are adenocarcinomas usually arising from an adenoma. Most rectal adenocarcinomas are characterised by chromosomal instability; microsatellite instability (MSI) is very rare (a few percent). Approximately one-third of rectal cancers are associated with aberrant DNA methylation. Several pathways are central to rectal cancer carcinogenesis, the WNT signalling pathways being the most important. The tumour suppressor gene APC is frequently mutated. Inactivation of additional tumour suppressor genes in the P53 and TGFβ pathways are seen, as well as activations of oncogenes such as KRAS and PI3CKA. BRAF mutations are rare in rectal cancer. Complete history and physical examination, complete blood count, liver and renal function tests, carcinoembryonic antigen, chest X-ray (alternatively computed tomography (CT) scan) and CT or magnetic resonance imaging (MRI) or ultrasound of liver and abdomen should be carried out. Endoscopic rectal ultrasound (ERUS) for the earliest tumours (cT1-T2) or rectal MRI for all tumours, including the earliest ones, is required in order to select patients for preoperative treatment and extent of surgery [2.Puli S.R. Reddy J.B. Bechtold M.L. et al.Accuracy of endoscopic ultrasound to diagnose nodal invasion by rectal cancers: a meta-analysis and systematic review.Ann Surg Oncol. 2009; 16: 1255-1265Crossref PubMed Scopus (131) Google Scholar, 3.Al-Sukhni E. Milot L. Fruitman M. et al.Diagnostic accuracy of MRI for assessment of T category, lymph node metastases, and circumferential resection margin involvement in patients with rectal cancer: a systematic review and meta-analysis.Ann Surg Oncol. 2012; 19: 2212-2223Crossref PubMed Scopus (364) Google Scholar] [III, A]. Preoperative complete colonoscopy is required. If the tumour is obstructive, virtual colonoscopy or barium enema is recommended also to exclude further manifestations (but regular colonoscopy should be added after resolution of the obstructive situation). Nodal staging is very unreliable even using both ERUS and MRI. In addition to large size (which in itself is not particularly accurate), roundness, irregular border and hypoechoic nature/heterogeneous signal on ERUS provide additional information. Histopathological examination should include surgical specimen with proximal, distal and circumferential margins and regional lymph nodes (it is recommended to examine at least 12 nodes). The pathohistological circumferential resection margin (crm) status is very important. There are uncertainties in the interpretation of this and the residual (R) tumour classification, and an expanded classification has been suggested [4.Wittekind C. Compton C. Quirke P. et al.A uniform residual tumor (R) classification: integration of the R classification and the circumferential margin status.Cancer. 2009; 115: 3483-3488Crossref PubMed Scopus (167) Google Scholar]. Moreover, vascular and nerve invasion should be evaluated [III, A]. The TNM staging system should be used. In these recommendations, version 7 (from 2010) is preferred, although version 5 is still used in some European countries. There is a need for further sub-classification of cT3, as indicated in Table 1. The TNM system is shown in Table 2, and stage grouping in Table 3.Table 1Diagnostic work-up in primary rectal cancerParameterMethod of choiceLocation (distance from anal verge)PalpationRigid sigmoidoscopy (flexible endoscopy)Morphological verificationBiopsyT stage EarlyERUSMRI Intermediate/advancedMRI (ERUS)Sphincter infiltrationMRI (ERUS, palpation)N stageMRI (CT, ERUS)M stageCT, MRI (or US) of the liver/abdomenCT/chest X-ray of the thoraxEvaluationMDT conferenceMRI, magnetic resonance imaging; ERUS, endorectal ultrasound; CT, computed tomography; US, ultrasound; MDT, multidisciplinary team. Methods within brackets are less optimal. Open table in a new tab Table 2TNM classification (version 7, 2010) with sub-classificationsTNMExtension toTisCarcinoma in situ: intraepithelial or invasion of lamina propriaT1SubmucosaT2Muscularis propriaT3Subserosa/perirectal tissueT3aaThis sub-classification based upon an evaluation using MRI before treatment decision is clinically valuable, and is used in these recommendations. It can be used also in the histopathological classification but is not validated and not incorporated in any of the TNM versions (5–7). <1 mmT3b 1–5 mmT3c 5–15 mmT3d 15+ mmT4Perforation into visceral peritoneum (a) or invasion to other organs (b)bThis is the sub-classification in TNM 6–7. It was the opposite in TNM 5. Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY.: Springer, 2010. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springer.com.N11–3 regional nodes involved N1a1 lymph node N1b2–3 lymph nodes N1cSmall deposits in the fatN24 or more regional nodes involved N2a4–6 lymph nodes N2b7 or more lymph nodesM1Distant metastases M1aOne distant organ or set of lymph nodes M1bMore than one organ or to the peritoneuma This sub-classification based upon an evaluation using MRI before treatment decision is clinically valuable, and is used in these recommendations. It can be used also in the histopathological classification but is not validated and not incorporated in any of the TNM versions (5–7).b This is the sub-classification in TNM 6–7. It was the opposite in TNM 5. Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY.: Springer, 2010. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springer.com. Open table in a new tab Table 3Stage groupingIT1-2, N0, M0IIAT3, N0, M0IIBT4a, N0, M0IICT4b, N0, M0IIIAT1-2, N1/N1c, M0T1, N2a, M0IIIBT3-T4a, N1/N1c, M0T2-T3, N2a, M0T1-2, N2b, M0IIICT4a, N2a, M0T3-4a, N2b, M0T4b, N1-2, M0IVAT1-4, N1-2, M1aIVBT1-4, N1-2, M1bEdge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY.: Springer, 2010. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springer.com. Open table in a new tab MRI, magnetic resonance imaging; ERUS, endorectal ultrasound; CT, computed tomography; US, ultrasound; MDT, multidisciplinary team. Methods within brackets are less optimal. Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY.: Springer, 2010. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springer.com. T1 tumours could also be classified according to Haggitt's sub-classification if the cancer is in a stalked adenoma and according to the Kikuchi (sm)-system if in a sessile adenoma [5.Haggitt R.C. Glotzbach R.E. Soffer E.E. Wruble L.D. Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polypectomy.Gastroenterology. 1985; 89: 328-336Abstract Full Text PDF PubMed Scopus (589) Google Scholar, 6.Kikuchi R. Takano M. Takagi K. et al.Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines.Dis Colon Rectum. 1995; 38: 1286-1295Crossref PubMed Scopus (543) Google Scholar] (Tables 4–5). The two systems overlap. The level of infiltration into the submucosa (sm) predicts the risk of lymph node metastases and thus the type of surgery [7.Sgourakis G. Lanitis S. Gockel I. et al.Transanal endoscopic microsurgery for T1 and T2 rectal cancers: a meta-analysis and meta-regression analysis of outcomes.Am Surg. 2011; 77: 761-772PubMed Google Scholar] [III, B]. In order to facilitate this sub-classification, these small lesions should be pinned-out on cork before being sent to the pathology laboratory.Table 4Haggitt's subclassification of polypoid T1 cancers based upon the extent of invasion of the stalkLevel0Absence of invasive carcinoma1Invasion into the head of the polyp2Invasion into the neck3Invasion into the stalk4Invasion into the baseEdge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY.: Springer, 2010. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springer.com. Open table in a new tab Table 5Subclassification of T1 cancers based upon depth of invasion into the submucosal layersm1Upper third2Middle third3Lower thirdNote: Haggitt's levels 1–3 correspond to sm 1, Haggitt's level 4 may be sm 1–3.Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY.: Springer, 2010. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springer.com. Open table in a new tab Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY.: Springer, 2010. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springer.com. Note: Haggitt's levels 1–3 correspond to sm 1, Haggitt's level 4 may be sm 1–3. Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY.: Springer, 2010. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, www.springer.com. Immunohistochemistry is helpful in identifying MSI tumours (although these are very rare in the rectum). An important aim is to treat so that the risk of residual disease in the pelvis, frequently causing a disabling local recurrence, is very low. This risk should preferably be less than about 5% in the population in whom curative treatment is intended, and, at the same time, as little acute and late morbidity as possible should be targeted. This should be possible in all but the few (≤10%) cases presenting with a fixed tumour growing into a non-readily resectable organ (some cT4b). Another aim is to treat such that a good sphincter function is preserved. From a practical point of view, rectal cancers could be divided into four groups:a.very early (some cT1),b.early (cT1-2, some cT3),c.intermediate (cT3- some cT4a)d.locally advanced (cT3crm +, some cT4a, all cT4b). Factors other than clinical T stage, such as tumour height, anterior location, proximity of the tumour or lymph node growths to the mesorectal fascia (mrf), size of the mesorectum, cN stage and vascular and nerve invasion are also relevant. It is presently not possible to give a precise definition of which T and N substages belong to these groups. The terms ‘favourable’ or ‘early’ or ‘good’, ‘intermediate’ or ‘bad’ and ‘locally advanced’ or ‘ugly’ can be used for categorising rectal cancers into clinical subgroups. In many of the recent studies, the term locally advanced has been commonly used for the intermediate/bad group, but is best reserved for the truly locally advanced/ugly tumours as used in the most recent European consensus documents [8.Valentini V. Aristei C. Glimelius B. et al.Multidisciplinary rectal cancer management: 2nd European Rectal Cancer Consensus Conference (EURECA-CC2).Radiother Oncol. 2009; 92: 148-163Abstract Full Text Full Text PDF PubMed Scopus (268) Google Scholar, 9.Glimelius B. Holm T. Blomqvist L. Chemotherapy in addition to preoperative radiotherapy in locally advanced rectal cancer—a systematic overview.Rev Recent Clin Trials. 2008; 3: 204-211Crossref PubMed Scopus (34) Google Scholar, 10.Schmoll H.J. Van Cutsem E. Stein A. et al.ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making.Ann Oncol. 2012; 23: 2479-2516Abstract Full Text Full Text PDF PubMed Scopus (1099) Google Scholar]. Extramural vascular invasion (EMVI) can be identified on MRI. Presence of EMVI (EMVI+) is a poor prognostic signal for development of distant metastases, and possibly also local failure. EMVI+ tumours belong at least to the intermediate group. Treatment of rectal cancer is demanding and requires highly skilled practice by the entire multidisciplinary team (MDT). Competent surgery and good pathology as well as sound radiation techniques and optimally given chemotherapy, together with long-term complete follow-up including also functional aspects, are important for quality control. Many countries have launched quality control programmes in rectal cancer surgery, which has been very beneficial for the outcomes. The quality of the mesorectal excision should be evaluated by the surgeon and/or the pathologist, as described elsewhere [11.Quirke P. Steele R. Monson J. et al.Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial.Lancet. 2009; 373: 821-828Abstract Full Text Full Text PDF PubMed Scopus (793) Google Scholar]. In the earliest, most favourable cases, chiefly the malignant polyps (Haggitt 1-3, T1 sm 1 (-2?) N0), a local procedure, e.g. using the transanal endoscopic microsurgery (TEM) technique, is appropriate [7.Sgourakis G. Lanitis S. Gockel I. et al.Transanal endoscopic microsurgery for T1 and T2 rectal cancers: a meta-analysis and meta-regression analysis of outcomes.Am Surg. 2011; 77: 761-772PubMed Google Scholar, 12.Doornebosch P.G. Tollenaar R.A. De Graaf E.J. Is the increasing role of transanal endoscopic microsurgery in curation for T1 rectal cancer justified? A systematic review.Acta Oncol. 2009; 48: 343-353Crossref PubMed Scopus (42) Google Scholar] [III, A]. The resection should be complete with safe margins (R0) and no signs of vessel invasion or poor differentiation should be present. If this is not the case or if the tumour infiltrates deeper into the submucosa (Haggit 4, T1 sm (2?-)3) or is a T2 tumour, the risk of recurrence due to remaining tumour cells or lymph node metastases is too high (≥10%) and immediate radical standard surgery (total mesorectal excision, TME) should be recommended [II, A]. Salvage surgery for local recurrence yields poor survival for a tumour initially staged T1. Chemoradiotherapy should be carried out only if surgery is contraindicated [III, C]. Local radiotherapy [brachytherapy or contact therapy (Papillon technique)] may be used as an alternative to local surgery, alone or with (preoperative) chemoradiotherapy [III, C]. Experience with these treatments outside specialised centres is limited [13.Gerard J.P. Ortholan C. Benezery K. et al.Contact X-ray therapy for rectal cancer: experience in Centre Antoine-Lacassagne, Nice, 2002–2006.Int J Radiat Oncol Biol Phys. 2008; 72: 665-670Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar]. In early, favourable cases (cT1-2, some early cT3, N0 [cT3a(-b) and clear mrf (mrf-) according to MRI], good group) above the levators, surgery alone, meaning a sharp radical dissection using the TME technique is appropriate [II, A], since the risk of local failure is very low [8.Valentini V. Aristei C. Glimelius B. et al.Multidisciplinary rectal cancer management: 2nd European Rectal Cancer Consensus Conference (EURECA-CC2).Radiother Oncol. 2009; 92: 148-163Abstract Full Text Full Text PDF PubMed Scopus (268) Google Scholar]. The role of TME in tumours situated in the upper third of the rectum has been much discussed and no strong evidence supporting TME in those cases has been reported. Instead, partial mesorectal excision can be carried out with a mesorectal margin of ≥5 cm distally to the tumour [IV, B]. In intermediate cases [most cT3 (cT3(b)c+ without threatened and involved mrf (mrf-) according to MRI], some cT4a (i.e. limited peritoneal involvement only), N+, bad group), preoperative radiotherapy is recommended followed by TME, since this reduces local recurrence rates [I, A]. Even in the absence of signs of extramural growth on ultrasound or MRI (cT2) in very low tumours (especially located anteriorly), preoperative radiotherapy may be indicated since the distance to the mrf is very small. This preoperative therapy could be given in one of two ways:a.either as short-course radiotherapy, 25 Gy, 5 Gy/fraction during 1 week followed by immediate surgery (<10 days from the first radiation fraction) [14.Sebag-Montefiore D. Stephens R.J. Steele R. et al.Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial.Lancet. 2009; 373: 811-820Abstract Full Text Full Text PDF PubMed Scopus (1153) Google Scholar, 15.Folkesson J. Birgisson H. Påhlman L. et al.Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate.J Clin Oncol. 2005; 23: 5644-5650Crossref PubMed Scopus (638) Google Scholar, 16.van Gijn W. Marijnen C.A. Nagtegaal I.D. et al.Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial.Lancet Oncol. 2011; 12: 575-582Abstract Full Text Full Text PDF PubMed Scopus (1250) Google Scholar] [I, A]b.or as 45–50.4 Gy, 1.8–2 Gy/fraction without or preferably with 5-fluorouracil (5-FU; bolus, continuous infusion or oral) [17.Bujko K. Nowacki M.P. Nasierowska-Guttmejer A. et al.Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer.Br J Surg. 2006; 93: 1215-1223Crossref PubMed Scopus (942) Google Scholar, 18.Gérard J.P. Conroy T. Bonnetain F. et al.Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: results of FFCD 9203.J Clin Oncol. 2006; 24: 4620-4625Crossref PubMed Scopus (1423) Google Scholar, 19.Bosset J.F. Collette L. Calais G. et al.Chemotherapy with preoperative radiotherapy in rectal cancer.N Engl J Med. 2006; 355: 1114-1123Crossref PubMed Scopus (2170) Google Scholar, 20.Ngan S.Y. Burmeister B. Fisher R.J. et al.Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04.J Clin Oncol. 2012; 30: 3827-3833Crossref PubMed Scopus (594) Google Scholar] [II, A]. Whenever possible, preoperative treatment is preferred because it is more effective and less toxic than postoperative treatment [8.Valentini V. Aristei C. Glimelius B. et al.Multidisciplinary rectal cancer management: 2nd European Rectal Cancer Consensus Conference (EURECA-CC2).Radiother Oncol. 2009; 92: 148-163Abstract Full Text Full Text PDF PubMed Scopus (268) Google Scholar, 21.Sauer R. Liersch T. Merkel S. et al.Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 Randomized Phase III Trial after a median follow-up of 11 years.J Clin Oncol. 2012; 30: 1926-1933Crossref PubMed Scopus (1393) Google Scholar] [I, A]. In locally advanced, sometimes non-resectable cases [cT3 mrf+, cT4 with overgrowth to organs not readily resectable (cT4b)], preoperative chemoradiotherapy (CRT), 50.4 Gy, 1.8 Gy/fraction with concomitant 5-FU-based therapy should be used [9.Glimelius B. Holm T. Blomqvist L. Chemotherapy in addition to preoperative radiotherapy in locally advanced rectal cancer—a systematic overview.Rev Recent Clin Trials. 2008; 3: 204-211Crossref PubMed Scopus (34) Google Scholar, 22.Braendengen M. Tveit K.M. Berglund Å et al.Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in non-resectable rectal cancer.J Clin Oncol. 2008; 26: 3687-3694Crossref PubMed Scopus (353) Google Scholar] [II, A]. This should be followed by radical surgery 6–8 weeks later. In very old patients (≥80–85 years) and in patients not fit for CRT, 5 × 5 Gy with a delay of ∼8 weeks before surgery is an option [23.Radu C. Berglund Å Påhlman L. Glimelius B. Short course preoperative radiotherapy with delayed surgery in rectal cancer—a retrospective study.Radiother Oncol. 2008; 87: 343-349Abstract Full Text Full Text PDF PubMed Scopus (177) Google Scholar, 24.Pettersson D. Holm T. Iversen H. et al.Preoperative short-course radiotherapy with delayed surgery in primary rectal cancer.Br J Surg. 2012; 99: 577-583Crossref PubMed Scopus (131) Google Scholar] [IV, A]. Standard preoperative chemoradiotherapy means a dose of 45–50.4 Gy, 1.8 Gy/fraction, or alternatively 50 Gy, 2 Gy/fraction together with a fluoropyrimidine, as trials have shown that chemoradiotherapy provides better local control than the same radiotherapy alone [9.Glimelius B. Holm T. Blomqvist L. Chemotherapy in addition to preoperative radiotherapy in locally advanced rectal cancer—a systematic overview.Rev Recent Clin Trials. 2008; 3: 204-211Crossref PubMed Scopus (34) Google Scholar, 18.Gérard J.P. Conroy T. Bonnetain F. et al.Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: results of FFCD 9203.J Clin Oncol. 2006; 24: 4620-4625Crossref PubMed Scopus (1423) Google Scholar, 19.Bosset J.F. Collette L. Calais G. et al.Chemotherapy with preoperative radiotherapy in rectal cancer.N Engl J Med. 2006; 355: 1114-1123Crossref PubMed Scopus (2170) Google Scholar, 22.Braendengen M. Tveit K.M. Berglund Å et al.Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in non-resectable rectal cancer.J Clin Oncol. 2008; 26: 3687-3694Crossref PubMed Scopus (353) Google Scholar] [I, A]. The fluoropyrimidine may be 5-FU given either as bolus injections with leucovorin (at 6–10 times during the radiation) [9.Glimelius B. Holm T. Blomqvist L. Chemotherapy in addition to preoperative radiotherapy in locally advanced rectal cancer—a systematic overview.Rev Recent Clin Trials. 2008; 3: 204-211Crossref PubMed Scopus (34) Google Scholar, 18.Gérard J.P. Conroy T. Bonnetain F. et al.Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: results of FFCD 9203.J Clin Oncol. 2006; 24: 4620-4625Crossref PubMed Scopus (1423) Google Scholar, 19.Bosset J.F. Collette L. Calais G. et al.Chemotherapy with preoperative radiotherapy in rectal cancer.N Engl J Med. 2006; 355: 1114-1123Crossref PubMed Scopus (2170) Google Scholar, 22.Braendengen M. Tveit K.M. Berglund Å et al.Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in non-resectable rectal cancer.J Clin Oncol. 2008; 26: 3687-3694Crossref PubMed Scopus (353) Google Scholar] or as prolonged continuous infusion (which is likely better than bolus [II, A]) or oral capecitabine [25.Hofheinz R.D. Wenz F. Post S. et al.Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial.Lancet Oncol. 2012; 13: 579-588Abstract Full Text Full Text PDF PubMed Scopus (376) Google Scholar]. Extrapolations from other clinical situations and convenience indicate that oral 5-FU is a valid treatment [I, A]. Combinations of 5-FU with other cytotoxics such as oxaliplatin or irinotecan or targeted biologic drugs have been extensively explored in phase II trials, with more favourable results claimed (more down-sizing, higher pathological complete regression (pCR) rates), but also more acute toxic effect. Early results of several comparative randomised trials have not been favourable (e.g. [26.Gérard J.P. Azria D. Gourgou-Bourgade S. et al.Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer.J Clin Oncol. 2012; 30: 4558-4565Crossref PubMed Scopus (310) Google Scholar]), and these combinations are still experimental. The choice of treatment according to risk category for primary rectal cancer without distant metastases is shown in Table 6.Table 6Choice of treatment according to risk category for primary rectal cancer without distant metastasesRisk groupTN substageTherapeutic optionsVery earlycT1 sm1 (-2?) N0Local excision (TEM). If poor prognostic signs (sm ≥ 2, high grade, V1), resection (TME) (or possibly CRT)Early (good)cT1-2; cT3a (b) if middle or high, N0 (or cN1 if high), mrf-, no EMVISurgery (TME) alone. If poor prognostic signs (crm+, N2) add postop CRT or CTaThe preoperative staging should be of such high quality so that this is rarely seen.. (CRT with evaluation, if cCR, wait-and-see, organ preservation)Intermediate (bad)cT2 very low, cT3mrf- (unless cT3a(b) and mid- or high rectum, N1-2, EMVI+, limited cT4aN0Preop RT (5 × 5 Gy) or CRT followed by TME. (if CRT and cCR, wait-and-see in high risk patients for surgery)Advanced (ugly)cT3mrf+, cT4a,b, lateral node+Preop CRT followed by surgery (TME + more extended surgery if needed due to tumour overgrowth). 5 × 5 Gy with a delay to surgery in elderly or in patients with severe comorbidity who cannot tolerate CRTOther factors than T and N stages are also relevant, such as distance from the anus and sphincters, direction, size of mesorectum and patient characteristics.TEM, transanal endoscopic microsurgery; TME, total mesorectal excision; CRT, chemoradiotherapy; RT, radiotherapy; cCR, clinical complete remission; CT, chemotherapy; EMVI, extramural vascular invasion; V1, vascular invasion.a The preoperative staging should be of such high quality so that this is rarely seen. Open table in a new tab Other factors than T and N stages are also relevant, such as distance from the anus and sphincters, direction, size of mesorectum and patient characteristics. TEM, transanal endoscopic microsurgery; TME, total mesorectal excision; CRT, chemoradiotherapy; RT, radiotherapy; cCR, clinical complete remission; CT, chemotherapy; EMVI, extramural vascular invasion; V1, vascular invasion. The standard of care today in rectal cancer surgery is TME implying that all of the mesorectal fat, including all lymph nodes, should be excised [III, A]. In rare situations a local excision can be an option in patients with a T1 tumour or in fragile patients with more advanced tumours. If this is the case, TEM is the procedure of choice. If an abdominal procedure is carried out, there are strong data indicating that a good TME without damaging the rectal fascia surrounding the mesorectal fat and rectum is prognostically relevant. If the fascia has been torn or damaged outcome is adversely affected and the local recurrence rate will increase. There is also good evidence indicating that surgeons can train and learn this technique and, once this technique has been adopted, the local recurrence rate will be reduced. If an abdominoperineal excision is planned, the dissection from above must be stopped at the tip of the coccyx and be continued from below in order to get a cylindrical specimen, without a waist effect towards the tumour carrying a risk of crm+ or an R1/2 resection [27.Holm T. Ljung A." @default.
• W2155492044 created "2016-06-24" @default.
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• W2155492044 date "2013-10-01" @default.
• W2155492044 modified "2023-10-11" @default.
• W2155492044 title "Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up" @default.
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