Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

The incidence of rectal cancer in the European Union is ∼125 000 per year, i.e. ∼35% of the total colorectal cancer incidence, reflecting 15–25 cases/100 000 population per year and is predicted to increase further in both genders. The mortality is 4–10/100 000 population per year. Median age at diagnosis is ∼70 years, but predictions suggest that this figure will rise in the future. Evidence is accumulating that rectal cancer is distinct from colon cancer with different aetiologies and risk factors [1.World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Report Summary.Food, Nutrition, Physical Activity, and the Prevention of Colorectal Cancer. 2011; Google Scholar, 2.Wei E.K. Giovannucci E. Wu K. et al.Comparison of risk factors for colon and rectal cancer.Int J Cancer. 2004; 108: 433-442Crossref PubMed Scopus (437) Google Scholar], possibly reflecting different environmental exposures. High body mass index, body or abdominal fatness and diabetes type II are seen as risk factors. Longstanding ulcerative colitis and Crohn’s disease affecting the rectum, excessive consumption of red or processed meat and tobacco as well as moderate/heavy alcohol use increase the risk. A healthy lifestyle and exercise can reduce the risk of developing rectal cancer [3.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: c5504.Crossref PubMed Scopus (140) Google Scholar, 4.Aleksandrova K. Pischon T. Jenab M. et al.Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study.BMC Med. 2014; 12: 168.Crossref PubMed Scopus (142) Google Scholar]. Consumption of garlic, milk, calcium and high dietary fibre are regarded as protective [5.Murphy N. Norat T. Ferrari P. et al.Dietary fibre intake and risks of cancers of the colon and rectum in the European prospective investigation into cancer and nutrition (EPIC).PLoS One. 2012; 7: e39361.Crossref PubMed Scopus (206) Google Scholar]. Although regular use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with reduced incidence, and there may be a protective effect of vitamin D via antitumour immunity, no formal guidelines for pharmacological primary prevention should be advised. The majority of rectal cancers develop via the chromosomal instability (CIN) pathway. About 13% are caused by deficient mismatch repair (dMMR). There is a recognised hereditary component, although this is more pronounced for colon than rectal cancer. The most common disorders are Lynch syndrome and familial adenomatous polyposis. Hence, genetic counselling is a critical component of management, driving surveillance and potential interventions for the patient and affected family members [6.Balmaña J. Balaguer F. Cervantes A. Arnold D. Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines.Ann Oncol. 2013; 24 (Suppl 6): vi73-vi80Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar]. Diagnosis is based on a digital rectal examination (DRE) and endoscopy with biopsy for histopathological confirmation (Figure 1). Tumours with distal extension to ≤ 15 cm from the anal margin (as measured by rigid sigmoidoscopy) are classified as rectal and more proximal tumours as colonic. Cancers are categorised as low (up to 5 cm), middle (from > 5 to 10 cm) or high (from > 10 up to 15 cm). The Cancer Genome Atlas Network analysis showed common genomic profiles for non-hypermutated colon and rectal cancers [7.Cancer Genome Atlas Network Comprehensive molecular characterization of human colon and rectal cancer.Nature. 2012; 487: 330-337Crossref PubMed Scopus (5937) Google Scholar]. Unique subtypes are characterised by accumulation of distinct genetic and epigenetic alterations (DNA methylation), differing slightly from colon cancer [8.Sadanandam A. Wang X. de Sousa E Melo F. et al.Reconciliation of classification systems defining molecular subtypes of colorectal cancer.Cell Cycle. 2014; 13: 353-357Crossref PubMed Scopus (57) Google Scholar, 9.Guinney J. Dienstmann R. Wang X. et al.The consensus molecular subtypes of colorectal cancer.Nat Med. 2015; 21: 1350-1356Crossref PubMed Scopus (2692) Google Scholar]. A transcriptional subtype with high Wnt signalling, stem cell and mesenchymal signatures occurs in rectal cancer and has a poor prognosis. Such patients may also gain less benefit from adjuvant chemotherapy (ChT) [10.Song N. Pogue-Geile K.L. Gavin P.G. et al.Clinical outcome from oxaliplatin treatment in stage II/III colon cancer according to intrinsic subtypes: secondary analysis of NSABP C-07/NRG oncology randomized clinical trial.JAMA Oncol. 2016; 2: 1162-1169Crossref PubMed Scopus (118) Google Scholar]. A specialised and dedicated multidisciplinary team (MDT) of named radiologists, surgeons, radiation oncologists, medical oncologists and pathologists should attend regular meetings and discuss all (relevant) patients [III, A]. Core members should be present for the discussion of all cases where their input is needed [11.National Cancer Action Team. The characteristics of an effective multidisciplinary team (MDT), 2010. www.ncin.org.uk/view?rid=136 (28 May 2017, date last accessed).Google Scholar]. There should be a MDT coordinator, and clinical guidelines should be taken into account in decision-making. The MDT should also audit whether their decisions are implemented [12.Munro A. Brown M. Niblock P. et al.Do multidisciplinary team (MDT) processes influence survival in patients with colorectal cancer? A population-based experience.BMC Cancer. 2015; 15: 686.Crossref PubMed Scopus (61) Google Scholar] and review patient outcomes with standardised quality assurance. A history and physical examination including DRE, full blood count, liver and renal function tests, serum carcinoembryonic antigen (CEA) and computed tomography (CT) scan of thorax and abdomen should be carried out to define functional status and presence of metastases [III, A] (Figure 2). Positron emission tomography (PET) may provide additional information in terms of disease outside the pelvis. However, current evidence is not considered strong enough to recommend the use of PET in all patients [V, C] (Table 1) [13.Van Cutsem E. Cervantes A. Adam R. et al.ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.Ann Oncol. 2016; 27: 1386-1422Abstract Full Text Full Text PDF PubMed Scopus (2095) Google Scholar].Table 1Diagnostic work-up in primary rectal cancerParameterMethod of choiceLocation (distance from anal verge)DRE/palpationRigid sigmoidoscopy (flexible endoscopy)Morphological verificationBiopsycT stage EarlyERUSMRI Intermediate/advancedMRI (ERUS)Sphincter infiltrationMRI (ERUS, palpation, EUA)cN stageMRI (CT, ERUS)M stageCT, MRI (or US) of the liver/abdomenCT of the thoraxPET-CT if extensive EMVI for other sitesEvaluation for all patientsMDT discussionMethods within brackets are less optimal.CT, computed tomography; DRE, digital rectal examination; EMVI, extramural vascular invasion; ERUS, endorectal ultrasound; EUA, examination under anaesthesia; MDT, multidisciplinary team; MRI, magnetic resonance imaging; PET, positron emission tomography; US, ultrasound. Open table in a new tab Methods within brackets are less optimal. CT, computed tomography; DRE, digital rectal examination; EMVI, extramural vascular invasion; ERUS, endorectal ultrasound; EUA, examination under anaesthesia; MDT, multidisciplinary team; MRI, magnetic resonance imaging; PET, positron emission tomography; US, ultrasound. Increasing age, comorbidity and decreasing functional reserves are associated with higher early postoperative mortality and worse toxicity from radiotherapy (RT) and ChT in older patients. Hence, for patients over 70 years, formal geriatric assessment or at least screening tools for frailty are recommended before any treatment [III, C] [14.Papamichael D. Audisio R.A. Glimelius B. et al.Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013.Ann Oncol. 2015; 26: 463-476Abstract Full Text Full Text PDF PubMed Scopus (261) Google Scholar]. Rigid rectoscopy and preoperative colonoscopy to the caecal pole are required, or, in the case of obstruction, virtual colonoscopy to exclude synchronous colonic tumours. If no preoperative (virtual) colonoscopy was carried out, completion colonoscopy is recommended within 6 months of surgery [III, A]. Endoscopic rectal ultrasound (ERUS) may define treatment for the earliest tumours. T1 tumours appropriate for transanal endoscopic microsurgery (TEM) can be selected by determining whether a lesion is limited to the mucosa or submucosa (sm) [15.Burdan F. Sudol-Szopinska I. Staroslawska E. et al.Magnetic resonance imaging and endorectal ultrasound for diagnosis of rectal lesions.Eur J Med Res. 2015; 20: 4.Crossref PubMed Scopus (25) Google Scholar]. ERUS offers less value in locally advanced rectal cancer (LARC). Pelvic magnetic resonance imaging (MRI) is the most accurate test to define locoregional clinical staging. By detecting extramural vascular invasion (EMVI), and determining the T substage and distance to the circumferential resection margin (CRM), MRI can also predict the risks of local recurrence and synchronous/metachronous distant metastases, and should be carried out to select patients for the respective preoperative management and to define the extent of surgery [III, A]. A standard proforma for MRI and pathology ensures a comprehensive report. The version of TNM staging used by the histopathologist and the MDT should be documented, acknowledged by all members of the MDT and regularly updated. The Union for International Cancer Control (UICC) TNM staging classification (8th edition) is shown in Table 2 [16.TNM Classification of Malignant Tumours.in: Brierley J.D. Gospodarowicz M.K. Wittekind C. 8th edition. John Wiley & Sons, Inc, Oxford2016Google Scholar].Table 2UICC TNM staging (8th edition) classification for colon and rectal cancer [16.TNM Classification of Malignant Tumours.in: Brierley J.D. Gospodarowicz M.K. Wittekind C. 8th edition. John Wiley & Sons, Inc, Oxford2016Google Scholar]TNM Clinical ClassificationT—Primary tumourTXPrimary tumour cannot be assessedT0No evidence of primary tumourTisCarcinoma in situ: invasion of lamina propriaaTis includes cancer cells confined within the mucosal lamina propria (intramucosal) with no extension through the muscularis mucosae into the submucosa.T1Tumour invades submucosaT2Tumour invades muscularis propriaT3Tumour invades subserosa or into non‐peritonealised pericolic or perirectal tissuesT4Tumour directly invades other organs or structuresbInvades through to visceral peritoneum to involve the surface., cDirect invasion in T4b includes invasion of other organs or segments of the colorectum by way of the serosa, as confirmed on microscopic examination, or for tumours in a retroperitoneal or subperitoneal location, direct invasion of other organs or structures by virtue of extension beyond the muscularis propria., dTumour that is adherent to other organs or structures, macroscopically, is classified cT4b. However, if no tumour is present in the adhesion, microscopically, the classification should be pT1–3, depending on the anatomical depth of wall invasion. and/or perforates visceral peritoneumT4aTumour perforates visceral peritoneumT4bTumour directly invades other organs or structuresN—Regional lymph nodesNXRegional lymph nodes cannot be assessedN0No regional lymph node metastasisN1Metastasis in 1–3 regional lymph nodesN1aMetastasis in 1 regional lymph nodeN1bMetastasis in 2–3 regional lymph nodesN1cTumour deposit(s), i.e. satellites,eTumour deposits (satellites) are discrete macroscopic or microscopic nodules of cancer in the pericolorectal adipose tissue’s lymph drainage area of a primary carcinoma that are discontinuous from the primary and without histological evidence of residual lymph node or identifiable vascular or neural structures. If a vessel wall is identifiable on H&E, elastic or other stains, it should be classified as venous invasion (V1/2) or lymphatic invasion (L1). Similarly, if neural structures are identifiable, the lesion should be classified as perineural invasion (Pn1). The presence of tumour deposits does not change the primary tumour T category, but changes the node status (N) to pN1c if all regional lymph nodes are negative on pathological examination. in the subserosa, or in non‐peritonealised pericolic or perirectal soft tissue without regional lymph node metastasisN2Metastasis in 4 or more regional lymph nodesN2aMetastasis in 4–6 regional lymph nodesN2bMetastasis in 7 or more regional lymph nodesM—Distant metastasisM0No distant metastasisM1Distant metastasisM1aMetastasis confined to one organ (liver, lung, ovary, non‐regional lymph node(s)) without peritoneal metastasesM1bMetastasis in more than one organM1cMetastasis to the peritoneum with or without other organ involvementH&E, hematoxilin and eosin; UICC, the Union for International Cancer Control; TNM, tumour, node, metastasis. Reprinted from [16.TNM Classification of Malignant Tumours.in: Brierley J.D. Gospodarowicz M.K. Wittekind C. 8th edition. John Wiley & Sons, Inc, Oxford2016Google Scholar], with permission from John Wiley & Sons, Inc.a Tis includes cancer cells confined within the mucosal lamina propria (intramucosal) with no extension through the muscularis mucosae into the submucosa.b Invades through to visceral peritoneum to involve the surface.c Direct invasion in T4b includes invasion of other organs or segments of the colorectum by way of the serosa, as confirmed on microscopic examination, or for tumours in a retroperitoneal or subperitoneal location, direct invasion of other organs or structures by virtue of extension beyond the muscularis propria.d Tumour that is adherent to other organs or structures, macroscopically, is classified cT4b. However, if no tumour is present in the adhesion, microscopically, the classification should be pT1–3, depending on the anatomical depth of wall invasion.e Tumour deposits (satellites) are discrete macroscopic or microscopic nodules of cancer in the pericolorectal adipose tissue’s lymph drainage area of a primary carcinoma that are discontinuous from the primary and without histological evidence of residual lymph node or identifiable vascular or neural structures. If a vessel wall is identifiable on H&E, elastic or other stains, it should be classified as venous invasion (V1/2) or lymphatic invasion (L1). Similarly, if neural structures are identifiable, the lesion should be classified as perineural invasion (Pn1). The presence of tumour deposits does not change the primary tumour T category, but changes the node status (N) to pN1c if all regional lymph nodes are negative on pathological examination. Open table in a new tab H&E, hematoxilin and eosin; UICC, the Union for International Cancer Control; TNM, tumour, node, metastasis. Reprinted from [16.TNM Classification of Malignant Tumours.in: Brierley J.D. Gospodarowicz M.K. Wittekind C. 8th edition. John Wiley & Sons, Inc, Oxford2016Google Scholar], with permission from John Wiley & Sons, Inc. High-quality MRI allows further subclassification of cT3, which is recommended as described in Table 3 [17.Zinicola R. Pedrazzi G. Haboubi N. Nicholls R.J. The degree of extramural spread of T3 rectal cancer: an appeal to the American Joint Committee on Cancer.Colorectal Dis. 2017; 19: 8-15Crossref PubMed Scopus (23) Google Scholar, 18.AJCC Cancer Staging Handbook.in: Edge S.B. Byrd D.R. Compton C.C. 7th edition. Springer, New York2010Google Scholar]. Stage grouping is shown in Table 4 [16.TNM Classification of Malignant Tumours.in: Brierley J.D. Gospodarowicz M.K. Wittekind C. 8th edition. John Wiley & Sons, Inc, Oxford2016Google Scholar].Table 3Subclassification of T3 rectal cancer [18.AJCC Cancer Staging Handbook.in: Edge S.B. Byrd D.R. Compton C.C. 7th edition. Springer, New York2010Google Scholar]Reprinted from [18.AJCC Cancer Staging Handbook.in: Edge S.B. Byrd D.R. Compton C.C. 7th edition. Springer, New York2010Google Scholar] with permission from Springer.Depth of invasion beyond the muscularis propria (in mm)T3aaThis 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).< 1T3b1–5T3c6–15T3d> 15MRI, magnetic resonance imaging; TNM, tumour, node, metastasis.a 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). Open table in a new tab Table 4Stage grouping of colon and rectal cancer [16.TNM Classification of Malignant Tumours.in: Brierley J.D. Gospodarowicz M.K. Wittekind C. 8th edition. John Wiley & Sons, Inc, Oxford2016Google Scholar]Reprinted from [16.TNM Classification of Malignant Tumours.in: Brierley J.D. Gospodarowicz M.K. Wittekind C. 8th edition. John Wiley & Sons, Inc, Oxford2016Google Scholar], with permission from John Wiley & Sons, Inc.TNM Pathological ClassificationThe pT and pN categories correspond to the T and N categories.pN0Histological examination of a regional lymphadenectomy specimen will ordinarily include 12 or more lymph nodes. If the lymph nodes are negative, but the number ordinarily examined is not met, classify as pN0.StageStage 0TisN0M0Stage IT1, T2N0M0Stage IIT3, T4N0M0Stage IIAT3N0M0Stage IIBT4aN0M0Stage IICT4bN0M0Stage IIIAny TN1, N2M0Stage IIIAT1, T2N1M0T1N2aM0Stage IIIBT1, T2N2bM0T2, T3N2aM0T3, T4aN1M0Stage IIICT3, T4aN2bM0T4aN2aM0T4bN1, N2M0Stage IVAny TAny NM1Stage IVAAny TAny NM1aStage IVBAny TAny NM1bStage IVCAny TAny NM1cTNM, tumour, node, metastasis. Open table in a new tab MRI, magnetic resonance imaging; TNM, tumour, node, metastasis. TNM, tumour, node, metastasis. Meta-analyses and population data show clinical nodal staging is unreliable even using ERUS, CT and MRI combined. The use of node size > 10 mm as a criterion for node-positive disease has been shown to be inaccurate. Irregular border and heterogeneous signal provide more relevant additional information [19.Brown G. Richards C.J. Bourne M.W. et al.Morphologic predictors of lymph node status in rectal cancer with use of high-spatial-resolution MR imaging with histopathologic comparison.Radiology. 2003; 227: 371-377Crossref PubMed Scopus (633) Google Scholar]. Nomograms have been suggested as a predictor of lymph node involvement but have yet to be validated [20.Liu Y. Wang R. Ding Y. et al.A predictive nomogram improved diagnostic accuracy and interobserver agreement of perirectal lymph nodes metastases in rectal cancer.Oncotarget. 2016; 7: 14755-14764Crossref PubMed Scopus (14) Google Scholar]. The assessment of the relationship between tumour and mesorectal fascia (MRF) is more crucial to decision-making than lymph node status. PET-CT should not be used routinely for initial staging, but can, in conjunction with liver MRI and contrast enhanced CT of the thorax, abdomen and pelvis be used to assess features at presentation associated with a high risk of metastases, e.g. extensive EMVI on MRI (see above) or high levels of CEA. Its value for assessment of primary tumour and nodal status is unproven, although it may assist RT target delineation. Bone scan and brain imaging should only be carried out if symptoms warrant. T1 tumours can be classified according to Haggitt’s subclassification if the cancer is pedunculated and according to the Kudo/Kikuchi sm-system if in a sessile adenoma [21.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, 22.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 (538) Google Scholar]. The two systems overlap. If sessile, the level of infiltration into the sm and the width of invasion compared with the width of the cancer should be assessed [23.Toh E.W. Brown P. Morris E. et al.Area of submucosal invasion and width of invasion predicts lymph node metastasis in pT1 colorectal cancers.Dis Colon Rectum. 2015; 58: 393-400Crossref PubMed Scopus (48) Google Scholar]. If pedunculated, the grade, lymphovascular invasion (LVI) and presence of budding predict the risk of lymph node metastases, enable a risk/benefit assessment of the requirement for further surgery and define the method of excision [III, B] [24.Sigourakis 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: 761-772Crossref PubMed Google Scholar]. These specimens should be pinned-out on cork before pathology assessment to facilitate this subclassification. Endoscopic resection for small tumours/polyps can be useful for both diagnosis and treatment, but en bloc resection is recommended for accurate assessment of invasion in the resection margin and the deepest area [II, B]. Piecemeal resection makes the specimen impossible to assess for the above and should be avoided. However, radical surgery and removal of lymph nodes is recommended for high-risk pathological features according to Japanese guidelines, i.e. poorly differentiated with evidence of vascular or lymphatic invasion, and an invasion depth of > 1000 micrometres [II, A] [25.Ikematsu H. Yoda Y. Matsuda T. et al.Long-term outcomes after resection for submucosal invasive colorectal cancers.Gastroenterology. 2013; 144: 551-559Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar]. For mesorectal resections, histopathological examination should include a photographic record of the surgical specimen and assessment of total mesorectal excision (TME) quality [III, B] [26.Hermanek P. Hermanek P. Hohenberger W. et al.The pathological assessment of mesorectal excision: implications for further treatment and quality management.Int J Colorectal Dis. 2003; 18: 335-341Crossref PubMed Scopus (70) Google Scholar, 27.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 (785) Google Scholar, 28.García-Granero E. Faiz O. Muñoz E. et al.Macroscopic assessment of mesorectal excision in rectal cancer: a useful tool for improving quality control in a multidisciplinary team.Cancer. 2009; 115: 3400-3411Crossref PubMed Scopus (71) Google Scholar], which is a strong quality control measure (Figure 3). The classification has three grades based on the completeness of the removal of the mesorectum and/or plane of surgical excision (Table 5) and impacts on both local recurrence and survival. Along with the involved CRM rate (i.e. ≤1 mm), TME quality represents a surrogate parameter for good oncological outcomes [29.Kreis M.E. Ruppert R. Ptok H. et al.Preoperative magnetic resonance imaging to select patients with rectal cancer for neoadjuvant chemoradiation–interim analysis of the German OCUM Trial (NCT01325649).J Gastrointest Surg. 2016; 20: 25-32Crossref PubMed Scopus (35) Google Scholar]. More advanced T-stage, tumour distance from the anal verge < 8 cm, more advanced age and low surgical case volume have been independently associated with moderate or poor TME quality [30.Garlipp B. Ptok H. Schmidt U. et al.Factors influencing the quality of total mesorectal excision.Br J Surg. 2012; 99: 714-720Crossref PubMed Scopus (39) Google Scholar].Table 5Grading of quality and completeness of the mesorectum in a total mesorectal excision specimen according to the plane of surgical excision [27.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 (785) Google Scholar]Mesorectal plane (good plane of surgery achieved)Intact mesorectum with only minor irregularities of a smooth mesorectal surface; no defect deeper than 5 mm; no coning; and smooth circumferential resection margin on slicingIntramesorectal plane (moderate plane of surgery achieved)Moderate bulk to mesorectum, with irregularities of the mesorectal surface; moderate distal coning; muscularis propria not visible with the exception of levator insertion; and moderate irregularities of circumferential resection marginMuscularis propria plane (poor plane of surgery achieved)Little bulk to mesorectum with defects down onto muscularis propria; very irregular circumferential resection margin; or bothThe specimen is examined as a whole (fresh) and as cross‐sectional slices (fixed) to make an adequate interpretation. A TME specimen ideally should have a smooth surface, without incisions, defects or cracks, as an indication of successful surgical excision of all mesorectal tissue. ‘Coning’ represents the tendency for the surgeon to cut inwards towards the central tube of the rectum during distal dissection, rather than staying outside the visceral mesorectal fascia. The specimen then shows a tapered, conical appearance representing suboptimal surgical quality.TME, total mesorectal excision.Reprinted from [27.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 (785) Google Scholar] with permission from Elsevier. Open table in a new tab The specimen is examined as a whole (fresh) and as cross‐sectional slices (fixed) to make an adequate interpretation. A TME specimen ideally should have a smooth surface, without incisions, defects or cracks, as an indication of successful surgical excision of all mesorectal tissue. ‘Coning’ represents the tendency for the surgeon to cut inwards towards the central tube of the rectum during distal dissection, rather than staying outside the visceral mesorectal fascia. The specimen then shows a tapered, conical appearance representing suboptimal surgical quality. TME, total mesorectal excision.Reprinted from [27.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 (785) Google Scholar] with permission from Elsevier. At least 12 regional lymph nodes should be examined. Proximal, distal and circumferential margins should be documented in millimetres (separately for tumour and involved lymph nodes). A proforma report such as the one by the Royal College of Pathologists is recommended [IV, B] [31.Quirke P. Williams G.T. Minimum Dataset for Colorectal Cancer Histopathology Reports. Royal College of Pathologists, London1998Google Scholar]. Uncertainties in the interpretation of CRM and the residual (R) tumour classification (and the distinction pT4/R1) according to the TNM version can cause confusion. An expanded classification has been suggested [32.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 (165) Google Scholar]. Extranodal extension (ENE) of nodal metastases, EMVI, perineural invasion (PNI) and tumour budding should also be evaluated [III, A]. Analysis of the rectal ‘doughnut’ is not required [IV, C] [33.Ng C.W. Lieske B. Tan K.K. Routine histological sampling of doughnuts post oncologic anterior resection is not necessary.Int J Colorectal Dis. 2014; 29: 843-845Crossref PubMed Scopus (9) Google Scholar]. Local excisional procedures such as TEM are appropriate as a single modality for early cancers (cT1N0 without adverse features like G3, V1, L1) [III, A] [34.Bach S.P. Hill J. Monson J.R. et al.A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer.Br J Surg. 2009; 96: 280-290Crossref PubMed Scopus (281) Google Scholar, 35.Junginger T. Goenner U. Hitzler M. et al.Long-term oncologic outcome after transanal endoscopic microsurgery for rectal carcinoma.Dis Colon Rectum. 2016; 59: 8-15Crossref PubMed Scopus (20) Google Scholar]. Only patients with cT1N0 should be considered for such treatment [36.Stornes T. Wibe A. Nesbakken A. et al.National early rectal cancer treatment revisited.Dis Colon Rectum. 2016; 59: 623-629Crossref PubMed Scopus (34) Google Scholar], although TEM for more advanced T-stage may be appropriate for patients at high surgical risk after discussion with the patient. TEM permits more accurate en bloc, full-thi