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Pre-operative staging of rectal cancer: MRI or ultrasound?
Seminars in Colon and Rectal Surgery 24 (2013) 114–118
Contents lists available at ScienceDirect
Seminars in Colon and Rectal Surgery journal homepage: www.elsevier.com/locate/yscrs
Pre-operative staging of rectal cancer: MRI or ultrasound? Manish Chand, BSc, MRCSa,b,n, Gina Brown, MD, FRCRb a b
Imperial College London, South Kensington Campus, London, UK Royal Marsden Hospital, Downs Road, Sutton, SM2 5PT, UK
a b s t r a c t Optimal management of rectal cancer depends on obtaining accurate and detailed staging information at the time of diagnosis. The majority of this comes from radiological staging investigations such as computed tomography (CT), magnetic resonance imaging (MRI) and endoanal ultrasound (EAUS). Whilst there is little debate on the use of CT to assess distant spread of disease, there is still variation in the use of MRI or EAUS in the local staging of rectal cancer. Both techniques have their roles but MRI is better able to visualise the entire rectum and mesorectum as well as accurately identify the circumferential resection (CRM) margin in relation to the tumour edge. Breach of the CRM is one of the most important predictors of local recurrence and knowledge of its relationship to the tumour determines initial management. MRI has additional advantages in being able to identify other poor prognostic factors such as extramural venous invasion (EMVI) and mucin deposition, which further influence oncological treatment. It also provides the surgeon with accurate information on the relationship of the tumour to surrounding structures and the sphincter complex which is important for surgical planning. This review highlights the important determinants of local staging in rectal cancer and presents the evidence to answer the question as to which is a better imaging modality—MRI or EAUS? & 2013 Elsevier Inc. All rights reserved.
1. Introduction
2. The mesorectum
Staging of local tumour spread is one of the most important aspects in the management of rectal cancer. The anatomy of the rectum within the narrow confines of the pelvis is complicated and knowledge of the relationship between the tumour and surrounding neurovascular and visceral structures is vital. Choosing the most appropriate imaging modality depends on being able to identify the key tumour features which are known to be associated with a poor prognosis. These factors include a combination of traditional staging information such as tumour depth, nodal disease and metastatic spread—TNM classification; as well as more novel morphological characteristics such as extramural venous invasion (EMVI) and proximity to the circumferential resection margin (CRM). The two common modalities used for local staging of rectal cancer are magnetic resonance imaging (MRI) and endoanal ultrasound (EAUS). Although both are considered to have specific benefits, MRI provides a more detailed picture of the locoregional anatomy of the pelvis and can accurately identify the specific features of the rectum which are considered important determinants in treatment decisions. We review the advantages of both EAUS and MRI with respect to local staging, to determine which technique is a most appropriate in the modern management of rectal cancer.
The rectum is surrounded by a lymphovascular envelope which acts as an oncological barrier to the spread of tumour. The outermost boundary of this fatty layer is defined by the mesorectal fascia (MRF). In the context of rectal cancer treatment and surgery in particular, it is known as the circumferential resection margin (CRM). The degree to which tumour is able to infiltrate this layer is an independent risk factor for local recurrence.1 This makes accurate identification of the mesorectum surrounding the tumour an important diagnostic challenge. Traditional staging classification systems have not included the depth of penetration into the mesorectum as standard. Increasing depth of invasion into the mesorectum is associated with worse survival and has led to a sub-classification within T-stage— T3a-d. Oncological surgery of the rectum involves excision of the tumour and the surrounding mesorectum—total mesorectal excision (TME).2 The lines of excision are defined by the embryological legacy of the primitive gut and are readily visible on MRI —Figure 1. This is the circumferential resection margin (CRM) and informs the surgeon of the likelihood of oncological clearance. Tumours which extend more than 5 mm into the mesorectum are considered poor prognostic tumours and are commonly offered neo-adjuvant therapy for down-staging thus decreasing the risk of a positive margin involvement after surgical resection.3
n
Corresponding author at: Royal Marsden Hospital Downs Road, Sutton, SM2 5PT UK E-mail address: [email protected] (M. Chand).
1043-1489/$ - see front matter & 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.scrs.2013.03.002
M. Chand, G. Brown / Seminars in Colon and Rectal Surgery 24 (2013) 114–118
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the assessment of the rectal wall and specifically, early lesions and polyps, due to its ability in highlighting the submucosal layer in detail. Some clinicians prefer the EAUS to plan for local resections where more radical oncological surgery is deemed not necessary. Figure 4 shows a typical scan image of EAUS of the rectum. There are important limitations with this technique though particularly if used as an alternative to MRI rather than complementing it. As it relies on insertion of a probe into the anal canal, it is not as accurate in staging “high” tumours which are at a distance from the probe. The biggest drawback of EAUS is that it cannot confidently identify the mesorectal fascia. As many treatment decisions are based on the relationship of the tumour to the MRF, it is not particularly useful in decision-making. This is also the case for assessment of tumour response following chemoradiotherapy.
Fig. 1. MRI demonstrating a rectal cancer in relation to the surrounding mesorectum (white arrow). The circumferential resection margin (red arrow) defines the lines of dissection. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
3. MRI—an overview MRI is arguably the most complete imaging modality for local staging of rectal cancer. However its accuracy depends on both user expertise as well as correct technique during the procedure. Correct field alignment through the long axis of the rectum is an important determinant of accuracy. This can be seen in Figure 2A. Incorrect positioning and technique will lead to over- or understaging of tumour depth and consequently influence treatment decisions (Fig. 2B and C). Ideally, one should use T2-weighted images for tumour detail. It may be necessary to use thin coronal sections for low tumours in addition to the sagittal images for planning and axial images through the field. Staging information depends on being able to accurately identify the layers of the rectal wall. In addition, identifying CRM and the involvement of local nodes influence treatment decisions. MRI is able to provide information on the rectal wall as well as regional information about the remainder of the pelvis and perineum. Other technical information can be seen on MRI such as the pre-sacral fascia, sphincter complex and peritoneal reflection (Fig. 3A and B).
4. Endoanal ultrasound—an overview Endoanal ultrasound uses a specialised probe inserted into the rectum to provide images of the rectal wall. The high spatial resolution of the images produced by EAUS is particularly useful in
5. Important factors in local staging Pre-operative staging demands accurate information of tumour characteristics and locoregional spread. This information influences treatment decisions and is related to the likelihood of future local and distant recurrence. These include tumour depth and relationship to the CRM, nodal disease, height of the tumour from the anal verge and presence of extramural venous invasion. We will examine these individual factors are best demonstrated and how they relate to the overall management of rectal cancer. The importance of accurate local staging has been reinforced by the shift towards neo-adjuvant treatment rather than adjuvant treatment whereby much of the oncological information could be obtained from histopathological analysis of the surgical specimen.
6. Tumour depth and CRM Tumour invasion through the rectal wall layers constitutes a main part of the traditional TNM staging system for rectal cancer. Tumour penetration is related to the individual layers of the bowel wall and Table 1 shows the T-stage. The risk of recurrence for T1, T2 and T3 tumours independent of lymph node involvement are in the order of 5%, 10%, and 25%, respectively4 Both MRI and EAUS are accurate in being able to identify the layers of the bowel wall. However, traditional T-staging has evolved as accurate T-staging has been shown to have implications on clinical outcome, particularly with regards to T3 tumours.5 The recognition of the importance of the mesorectal fascia which bounds the mesorectum surrounding the rectum has meant that for optimal decision-making identification of the MRF is essential. Tumour penetration into the mesorectum can be identified within millimetres using MRI.6 Ensuring clearance from the circumferential
Fig. 2. (A) The correct field lies perpendicular to the long axis of the rectum. The sections are shown by the thin white lines on the left image resulting in the axial image on the right. (B) If the field alignment is not perpendicular to the long axis of the rectum it may incorrectly stage the patient. The dotted line shows the field lined up at a greater angle than 901. (C) The incorrect field alignment may not accurately depict the relationship of the tumour to the important lines of dissection.
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Table 1 T-staging of rectal cancer. Primary tumour (T) TX T0 Tis T1 T2 T3 T4
Fig. 3. (A) The sagittal section shows the pre-sacral fascia depicted by the white arrow. (B) Sagittal section showing peritoneal reflection.
resection margin is necessary to avoid local recurrence. Breach of tumour into the CRM is a positive predictive factor for local recurrence.7 The accuracy of MRI to identify the CRM is its main advantage it has over EAUS. The clearance from the CRM is also an important determinant of prognosis. Minimal penetration of the tumour into the mesorectum has the best outcomes. Indeed, those tumours which show a breach of less than 1 mm into the mesorectum have similar outcomes as T2 tumours.8 In a more recent study, tumour distance within 1 mm of the CRM has been shown to have a local recurrence rate of 53% which falls to 8% when there is clearance of between 1 and 5 mm.1 This highlights the importance of being able to accurately identify the depth of tumour invasion into the mesorectum within millimetres, something which MRI is capable of. Historically, there has been a challenge in being able to reproducibly identify the CRM at 1 mm with the suggestion that a cut-off of 5 mm is needed to show correlation with a negative CRM on histology. However, recent studies have challenged this and measuring depth of invasion to 1 mm is possible9 which results in more accurate staging and thus reduces the number of patients who would be undergoing CRT on the basis of inaccurate staging.10 The importance of tumour penetration into the mesorectum and the effect on local recurrence rates has led to a subclassification of T-stage and in particular T3 tumours. Jass et al.11 originally described the difference in outcomes related to the extent of mesorectal invasion. Further work by Cawthron and Merkel8,12 confirmed the importance of mesorectal spread. The T3 sub-classification is shown in Table 2. This has led to local staging imaging being required not only to identify the CRM but also accurately describe the extent of tumour spread into the mesorectum. Early T3 tumour, that is T3a and T3b, offer good prognosis and will show little benefit from CRT providing the tumour shows
Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in-situ Tumour invades submucosa Tumour invades muscularis propria Tumour invades through muscularis propria into the subserosa Tumour directly invades other structures and/or perforates visceral peritoneum
no other adverse features.1 Figure 5 shows a T3c rectal cancer with invasion into the mesorectum. Tumour depth is an important issue in early cancers as well as more advanced breaches into the mesorectum. We have already described the basis of TME which has been universally accepted as the “gold standard” for oncological surgery of the rectum. However, TME is radical surgery and although technique continues to be refined there is, of course, morbidity associated with such surgery. Some early tumours which do not display adverse features are suitable for a local procedure which does not necessarily require formal bowel resection. EAUS has been thought of as particularly useful in this context. And whilst there may be a role its use in such situations, it has been shown to have poor accuracy in distinguishing invasion in early villous lesions/polyps larger than 5-mm height.13 This inaccurate staging is due to the lack of penetration of the high resolution probe. A recent analysis of the use of EAUS in decision-making for transanal endoscopic microsurgery of the rectum has shown EUAS not to be as accurate as previously thought.14 A current trial focussed on short-course neoadjuvant treatment and a local excision as opposed to TME for early cancers is also evaluating the role of MRI and EAUS in these tumours (Transanal Endoscopic Microsurgery and Radiotherapy in Early Cancer—TREC). Clearly, there is a need to prospectively investigate the use of MRI and its accuracy in detection of early lesions.
7. Nodal disease Nodal involvement is still an important consideration in treatment planning. It is part of the TNM classification and the presence of nodal disease is a determinant in the use of CRT prior to surgery. However, accurate identification of involved lymph nodes has traditionally been a challenging issue. Whilst lymph nodes may be readily identified on EAUS or MRI, the question of malignancy in the node has remained a difficult one. The predictive value of using size as a marker for tumour involvement in local lymph nodes is poor and nodes should not be assessed on size alone. Such an approach would lead to considerable over-staging and ultimately over-treatment as many reactive nodes would be considered to be malignant. A better approach is nodal morphology and imaging characteristics. Using features of nodal border, contour and differing signal characteristics the sensitivity and specificity Table 2 T3 sub-classification in rectal cancer.
Fig. 4. A typical image on endoanal ultrasound.
T-stage
Depth of extramural spread (mm)
T3a T3b T3c T3d
o1.00 1.01–5.00 5.01–15.00 415.00
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examination; however MRI can provide accurate description of the tumour in relation to the anal verge and to other important components of the pelvis such as the levators and peritoneal reflection. For low rectal tumours, those which extend into the intersphincteric plane are most likely to lead to local recurrence and would most benefit from neo-adjuvant therapy. This can be identified pre-operatively on MRI.18 EAUS is not as accurate when describing low tumours, however this relates more to the additional staging information. The benefit of MRI over EAUS and rigid sigmoidoscopy lies in its ability to describe the extent of the tumour, not just the height of the tumour edge. This information greatly helps the surgeon plan the most appropriate operation.
9. Extramural venous invasion
Fig. 5. The tumour is penetrating into the surrounding mesorectum. The extent of spread in this image is more than 5 mm which is a poor prognostic marker.
increases to 85% and 97%, respectively.15 Figure 6 shows a malignant node on MRI. EUAS has a sensitivity and specificity for detection of cancerous lymph nodes in rectal cancer of 73% and 75%,16 respectively and is more likely to be accurate in more proximal rectum. It also has great difficulty in identifying nodes which are less than 5 mm in size. EAUS cannot interrogate the entire mesorectum and therefore cannot assess the lymph node status in the areas of the mesorectum it does not visualise. This may lead to under-staging of disease.
8. Height of tumour Defining the height of tumour is an important factor when considering the most appropriate form of surgical treatment, and in some cases, deciding on whether CRT may help in performing a less radical operation—will the patient need an anterior resection, abdominoperineal resection, defunctioning stoma, an extralevator operation? Tumours defined as “low rectal cancer” are within 5 cm of the anal verge and are more likely to lead to local recurrence.17 Tradition would lead us to believe that tumour height is best measured on rigid sigmoidoscopy or with a finger on rectal
Fig. 6. A malignant node on MRI.
Extramural vascular invasion (EMVI) is defined as the presence of malignant cells in the vasculature beyond the muscularis propria surrounding the tumour. It is known to be a stageindependent factor of poor prognosis in rectal cancer19 and is associated with an increased risk of local recurrence and distant metastases.20 The presence of EMVI in colorectal cancer is seen in as much as 50% of tumours but is almost always associated with more advanced stage—T3 and T4 tumours.21 Patients with EMVI as a feature of the tumour have a 50% chance of developing metastases compared with 12% in EMVI negative patients. Yet there is relatively little known about this phenomenon. It is almost exclusively seen in T3 and T4 tumours and may be the natural progression of intramural vascular spread. EAUS has no effective ability to distinguish normal vessels from those which have been infiltrated with tumour. MRI shows a characteristic serpiginous extension of tumour signal into perirectal fat.22 The fact that this is only seen in T3 and T4 tumours is understandable as a tumour which is limited to muscularis propria will be unlikely to have tumour spread into extramural veins. This is shown in Figure 7. Assessment of EMVI using MRI must consider the following components: pattern of tumour margin which gives the appearance of nodularity; location of tumour to relevant vessels which makes tumour invasion more likely; calibre of vessel as tumour infiltration can cause an increase in luminal size; and vessel border if the tumour disrupts the vessel itself.23 Table 3 shows the EMVI classification based on MRI appearance.
Fig. 7. The sagittal section shows tumour penetrating into the extramural vasculature beyond the muscularis (white arrow).
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References
Table 3 EMVI classification. MRI-EMVI score
EMVI status
Description
0 1 2
Negative Negative Negative
3 4
Positive Positive
No vessels adjacent to areas of tumour penetration Minimal stranding but well away from vessels Stranding within vicinity of vessel but no definite tumour signal Intermediate signal within slightly expanded vessel Irregular contour of vessel by definite tumour signal
10. Clinical considerations of MRI or EAUS MRI has become the imaging modality of choice in the UK and Europe but is not so popular in the US. This may be partly explained by the differing approaches to neo-adjuvant treatment. MRI has the advantage of recognising the adverse features which make a tumour “high-risk” and therefore more likely to benefit from neo-adjuvant treatment. This means that patients are selected on the basis of highrisk features identified on imaging as much of this information is lacking from biopsy material. The perceived advantage of being more selective is that patients may not have to undergone additional treatments with little benefit. Both techniques have their advantages however these must be appreciated in terms of clinical approach. Certainly, a more tailored approach would allow the use of the most appropriate technique for any given situation. In the past, any T3 would have been considered for neoadjuvant therapy. However on more detailed analysis of imaging and outcomes this results in overtreatment to the detriment of sphincter function and anastomotic healing. It is therefore logical to consider this risk in terms of recurrence—those tumours which are involving the CRM but without other adverse features; patients who are at risk of distant recurrence but would not benefit from local radiotherapy as much as systemic treatment; and finally those who are at risk of both types of recurrence who need the most aggressive pre-operative strategy. 11. Conclusion MRI and EAUS are individually advantageous in the local staging of rectal cancer. MRI is an overall better imaging modality as it is able to provide accurate detail on the tumour spread as well as the relationship to important features within the pelvis. EAUS is particularly useful for early tumours and the planning of local resection procedures. The decision as to which modality to use depends on the treatment policy with regards to oncological therapy. For a more selective approach where patients with high-risk tumours are offered neo-adjuvant treatment, MRI is a superior imaging tool. However this comes against increased cost and user expertise.
1. Taylor FG, et al. One millimetre is the safe cut-off for magnetic resonance imaging prediction of surgical margin status in rectal cancer. Br J Surg. 2011; 98(6):872–879. 2. Heald RJ, Husband EM, Ryall RD. The mesorectum in rectal cancer surgery—the clue to pelvic recurrence? BrJ Surg. 1982;69(10):613–616. 3. Beets-Tan RG, et al. Accuracy of magnetic resonance imaging in prediction of tumour-free resection margin in rectal cancer surgery. Lancet. 2001; 357(9255):497–504. 4. Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer. 2010;116(22):5336–5339. 5. Willett CG, Badizadegan K, Ancukiewicz M, Shellito PC. Prognostic factors in stage T3N0 rectal cancer: do all patients require postoperative pelvic irradiation and chemotherapy? Dis Colon Rectum. 1999;42(2):167–173. 6. Taylor FG, et al. Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study. Ann Surg. 2011; 253(4):711–719. 7. Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet. 1986;2(8514):996–999. 8. Merkel S, Mansmann U, Siassi M, Papadopoulos T, Hohenberger W, Hermanek P. The prognostic inhomogeneity in pT3 rectal carcinomas. Int J Colorectal Dis. 2001;16(5):298–304. 9. MERCURY Study Group. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. Br Med J, 2006. 10. Strassburg J, et al. Magnetic resonance imaging (MRI)-based indication for neoadjuvant treatment of rectal carcinoma and the surrogate endpoint CRM status. Int J Colorectal Dis. 2008;23(11):1099–1107. 11. Jass JR, Love SB, Northover JM. A new prognostic classification of rectal cancer. Lancet. 1987;1(8545):1303–1306. 12. Cawthorn SJ, et al. Extent of mesorectal spread and involvement of lateral resection margin as prognostic factors after surgery for rectal cancer. Lancet. 1990;335(8697):1055–1059. 13. Konishi K, et al. Evaluation of endoscopic ultrasonography in colorectal villous lesions. Int J Colorectal Dis. 2003;18(1):19–24. 14. Ashraf S, et al. A critical appraisal of endorectal ultrasound and transanal endoscopic microsurgery and decision-making in early rectal cancer. Colorectal Dis. 2012;14(7):821–826. 15. Brown G, 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(2):371–377. 16. Puli SR, Reddy JB, Bechtold ML, Choudhary A, Antillon MR, Brugge WR. Accuracy of endoscopic ultrasound to diagnose nodal invasion by rectal cancers: a metaanalysis and systematic review. Ann Surg Oncol. 2009;16(5):1255–1265. 17. Faerden AE, et al. Total mesorectal excision for rectal cancer: difference in outcome for low and high rectal cancer. Dis Colon Rectum. 2005;48(12):2224–2231. 18. Salerno GV, Daniels IR, Moran BJ, Heald RJ, Thomas K, Brown G. Magnetic resonance imaging prediction of an involved surgical resection margin in low rectal cancer. Dis Colon Rectum. 2009;52(4):632–639. 19. Dresen RC, et al. Local recurrence in rectal cancer can be predicted by histopathological factors. Eur J Surg Oncol. 2009;35(10):1071–1077. 20. Talbot IC, Ritchie S, Leighton MH, Hughes AO, Bussey HJ, Morson BC. The clinical significance of invasion of veins by rectal cancer. Br J Surg. 1980;67(6):439–442. 21. Smith NJ, Barbochano Y, Norman AR, Swift RI, Abulafi AM, Brown G. Prognostic significance of magnetic resonance imaging-detected extramural vascular invasion in rectal cancer. Br J Surg. 2008;95(2):229–236. 22. Smith NJ, Shihab O, Arnaout A, Swift RI, Brown G. MRI for detection of extramural vascular invasion in rectal cancer. Am J Roentgenol. 2008;191 (5):1517–1522. 23. Kwok H, Bissett IP, Hill GL. Preoperative staging of rectal cancer. Int J Colorectal Dis. 2000;15(1):9–20.
Contents lists available at ScienceDirect
Seminars in Colon and Rectal Surgery journal homepage: www.elsevier.com/locate/yscrs
Pre-operative staging of rectal cancer: MRI or ultrasound? Manish Chand, BSc, MRCSa,b,n, Gina Brown, MD, FRCRb a b
Imperial College London, South Kensington Campus, London, UK Royal Marsden Hospital, Downs Road, Sutton, SM2 5PT, UK
a b s t r a c t Optimal management of rectal cancer depends on obtaining accurate and detailed staging information at the time of diagnosis. The majority of this comes from radiological staging investigations such as computed tomography (CT), magnetic resonance imaging (MRI) and endoanal ultrasound (EAUS). Whilst there is little debate on the use of CT to assess distant spread of disease, there is still variation in the use of MRI or EAUS in the local staging of rectal cancer. Both techniques have their roles but MRI is better able to visualise the entire rectum and mesorectum as well as accurately identify the circumferential resection (CRM) margin in relation to the tumour edge. Breach of the CRM is one of the most important predictors of local recurrence and knowledge of its relationship to the tumour determines initial management. MRI has additional advantages in being able to identify other poor prognostic factors such as extramural venous invasion (EMVI) and mucin deposition, which further influence oncological treatment. It also provides the surgeon with accurate information on the relationship of the tumour to surrounding structures and the sphincter complex which is important for surgical planning. This review highlights the important determinants of local staging in rectal cancer and presents the evidence to answer the question as to which is a better imaging modality—MRI or EAUS? & 2013 Elsevier Inc. All rights reserved.
1. Introduction
2. The mesorectum
Staging of local tumour spread is one of the most important aspects in the management of rectal cancer. The anatomy of the rectum within the narrow confines of the pelvis is complicated and knowledge of the relationship between the tumour and surrounding neurovascular and visceral structures is vital. Choosing the most appropriate imaging modality depends on being able to identify the key tumour features which are known to be associated with a poor prognosis. These factors include a combination of traditional staging information such as tumour depth, nodal disease and metastatic spread—TNM classification; as well as more novel morphological characteristics such as extramural venous invasion (EMVI) and proximity to the circumferential resection margin (CRM). The two common modalities used for local staging of rectal cancer are magnetic resonance imaging (MRI) and endoanal ultrasound (EAUS). Although both are considered to have specific benefits, MRI provides a more detailed picture of the locoregional anatomy of the pelvis and can accurately identify the specific features of the rectum which are considered important determinants in treatment decisions. We review the advantages of both EAUS and MRI with respect to local staging, to determine which technique is a most appropriate in the modern management of rectal cancer.
The rectum is surrounded by a lymphovascular envelope which acts as an oncological barrier to the spread of tumour. The outermost boundary of this fatty layer is defined by the mesorectal fascia (MRF). In the context of rectal cancer treatment and surgery in particular, it is known as the circumferential resection margin (CRM). The degree to which tumour is able to infiltrate this layer is an independent risk factor for local recurrence.1 This makes accurate identification of the mesorectum surrounding the tumour an important diagnostic challenge. Traditional staging classification systems have not included the depth of penetration into the mesorectum as standard. Increasing depth of invasion into the mesorectum is associated with worse survival and has led to a sub-classification within T-stage— T3a-d. Oncological surgery of the rectum involves excision of the tumour and the surrounding mesorectum—total mesorectal excision (TME).2 The lines of excision are defined by the embryological legacy of the primitive gut and are readily visible on MRI —Figure 1. This is the circumferential resection margin (CRM) and informs the surgeon of the likelihood of oncological clearance. Tumours which extend more than 5 mm into the mesorectum are considered poor prognostic tumours and are commonly offered neo-adjuvant therapy for down-staging thus decreasing the risk of a positive margin involvement after surgical resection.3
n
Corresponding author at: Royal Marsden Hospital Downs Road, Sutton, SM2 5PT UK E-mail address: [email protected] (M. Chand).
1043-1489/$ - see front matter & 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.scrs.2013.03.002
M. Chand, G. Brown / Seminars in Colon and Rectal Surgery 24 (2013) 114–118
115
the assessment of the rectal wall and specifically, early lesions and polyps, due to its ability in highlighting the submucosal layer in detail. Some clinicians prefer the EAUS to plan for local resections where more radical oncological surgery is deemed not necessary. Figure 4 shows a typical scan image of EAUS of the rectum. There are important limitations with this technique though particularly if used as an alternative to MRI rather than complementing it. As it relies on insertion of a probe into the anal canal, it is not as accurate in staging “high” tumours which are at a distance from the probe. The biggest drawback of EAUS is that it cannot confidently identify the mesorectal fascia. As many treatment decisions are based on the relationship of the tumour to the MRF, it is not particularly useful in decision-making. This is also the case for assessment of tumour response following chemoradiotherapy.
Fig. 1. MRI demonstrating a rectal cancer in relation to the surrounding mesorectum (white arrow). The circumferential resection margin (red arrow) defines the lines of dissection. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
3. MRI—an overview MRI is arguably the most complete imaging modality for local staging of rectal cancer. However its accuracy depends on both user expertise as well as correct technique during the procedure. Correct field alignment through the long axis of the rectum is an important determinant of accuracy. This can be seen in Figure 2A. Incorrect positioning and technique will lead to over- or understaging of tumour depth and consequently influence treatment decisions (Fig. 2B and C). Ideally, one should use T2-weighted images for tumour detail. It may be necessary to use thin coronal sections for low tumours in addition to the sagittal images for planning and axial images through the field. Staging information depends on being able to accurately identify the layers of the rectal wall. In addition, identifying CRM and the involvement of local nodes influence treatment decisions. MRI is able to provide information on the rectal wall as well as regional information about the remainder of the pelvis and perineum. Other technical information can be seen on MRI such as the pre-sacral fascia, sphincter complex and peritoneal reflection (Fig. 3A and B).
4. Endoanal ultrasound—an overview Endoanal ultrasound uses a specialised probe inserted into the rectum to provide images of the rectal wall. The high spatial resolution of the images produced by EAUS is particularly useful in
5. Important factors in local staging Pre-operative staging demands accurate information of tumour characteristics and locoregional spread. This information influences treatment decisions and is related to the likelihood of future local and distant recurrence. These include tumour depth and relationship to the CRM, nodal disease, height of the tumour from the anal verge and presence of extramural venous invasion. We will examine these individual factors are best demonstrated and how they relate to the overall management of rectal cancer. The importance of accurate local staging has been reinforced by the shift towards neo-adjuvant treatment rather than adjuvant treatment whereby much of the oncological information could be obtained from histopathological analysis of the surgical specimen.
6. Tumour depth and CRM Tumour invasion through the rectal wall layers constitutes a main part of the traditional TNM staging system for rectal cancer. Tumour penetration is related to the individual layers of the bowel wall and Table 1 shows the T-stage. The risk of recurrence for T1, T2 and T3 tumours independent of lymph node involvement are in the order of 5%, 10%, and 25%, respectively4 Both MRI and EAUS are accurate in being able to identify the layers of the bowel wall. However, traditional T-staging has evolved as accurate T-staging has been shown to have implications on clinical outcome, particularly with regards to T3 tumours.5 The recognition of the importance of the mesorectal fascia which bounds the mesorectum surrounding the rectum has meant that for optimal decision-making identification of the MRF is essential. Tumour penetration into the mesorectum can be identified within millimetres using MRI.6 Ensuring clearance from the circumferential
Fig. 2. (A) The correct field lies perpendicular to the long axis of the rectum. The sections are shown by the thin white lines on the left image resulting in the axial image on the right. (B) If the field alignment is not perpendicular to the long axis of the rectum it may incorrectly stage the patient. The dotted line shows the field lined up at a greater angle than 901. (C) The incorrect field alignment may not accurately depict the relationship of the tumour to the important lines of dissection.
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M. Chand, G. Brown / Seminars in Colon and Rectal Surgery 24 (2013) 114–118
Table 1 T-staging of rectal cancer. Primary tumour (T) TX T0 Tis T1 T2 T3 T4
Fig. 3. (A) The sagittal section shows the pre-sacral fascia depicted by the white arrow. (B) Sagittal section showing peritoneal reflection.
resection margin is necessary to avoid local recurrence. Breach of tumour into the CRM is a positive predictive factor for local recurrence.7 The accuracy of MRI to identify the CRM is its main advantage it has over EAUS. The clearance from the CRM is also an important determinant of prognosis. Minimal penetration of the tumour into the mesorectum has the best outcomes. Indeed, those tumours which show a breach of less than 1 mm into the mesorectum have similar outcomes as T2 tumours.8 In a more recent study, tumour distance within 1 mm of the CRM has been shown to have a local recurrence rate of 53% which falls to 8% when there is clearance of between 1 and 5 mm.1 This highlights the importance of being able to accurately identify the depth of tumour invasion into the mesorectum within millimetres, something which MRI is capable of. Historically, there has been a challenge in being able to reproducibly identify the CRM at 1 mm with the suggestion that a cut-off of 5 mm is needed to show correlation with a negative CRM on histology. However, recent studies have challenged this and measuring depth of invasion to 1 mm is possible9 which results in more accurate staging and thus reduces the number of patients who would be undergoing CRT on the basis of inaccurate staging.10 The importance of tumour penetration into the mesorectum and the effect on local recurrence rates has led to a subclassification of T-stage and in particular T3 tumours. Jass et al.11 originally described the difference in outcomes related to the extent of mesorectal invasion. Further work by Cawthron and Merkel8,12 confirmed the importance of mesorectal spread. The T3 sub-classification is shown in Table 2. This has led to local staging imaging being required not only to identify the CRM but also accurately describe the extent of tumour spread into the mesorectum. Early T3 tumour, that is T3a and T3b, offer good prognosis and will show little benefit from CRT providing the tumour shows
Primary tumour cannot be assessed No evidence of primary tumour Carcinoma in-situ Tumour invades submucosa Tumour invades muscularis propria Tumour invades through muscularis propria into the subserosa Tumour directly invades other structures and/or perforates visceral peritoneum
no other adverse features.1 Figure 5 shows a T3c rectal cancer with invasion into the mesorectum. Tumour depth is an important issue in early cancers as well as more advanced breaches into the mesorectum. We have already described the basis of TME which has been universally accepted as the “gold standard” for oncological surgery of the rectum. However, TME is radical surgery and although technique continues to be refined there is, of course, morbidity associated with such surgery. Some early tumours which do not display adverse features are suitable for a local procedure which does not necessarily require formal bowel resection. EAUS has been thought of as particularly useful in this context. And whilst there may be a role its use in such situations, it has been shown to have poor accuracy in distinguishing invasion in early villous lesions/polyps larger than 5-mm height.13 This inaccurate staging is due to the lack of penetration of the high resolution probe. A recent analysis of the use of EAUS in decision-making for transanal endoscopic microsurgery of the rectum has shown EUAS not to be as accurate as previously thought.14 A current trial focussed on short-course neoadjuvant treatment and a local excision as opposed to TME for early cancers is also evaluating the role of MRI and EAUS in these tumours (Transanal Endoscopic Microsurgery and Radiotherapy in Early Cancer—TREC). Clearly, there is a need to prospectively investigate the use of MRI and its accuracy in detection of early lesions.
7. Nodal disease Nodal involvement is still an important consideration in treatment planning. It is part of the TNM classification and the presence of nodal disease is a determinant in the use of CRT prior to surgery. However, accurate identification of involved lymph nodes has traditionally been a challenging issue. Whilst lymph nodes may be readily identified on EAUS or MRI, the question of malignancy in the node has remained a difficult one. The predictive value of using size as a marker for tumour involvement in local lymph nodes is poor and nodes should not be assessed on size alone. Such an approach would lead to considerable over-staging and ultimately over-treatment as many reactive nodes would be considered to be malignant. A better approach is nodal morphology and imaging characteristics. Using features of nodal border, contour and differing signal characteristics the sensitivity and specificity Table 2 T3 sub-classification in rectal cancer.
Fig. 4. A typical image on endoanal ultrasound.
T-stage
Depth of extramural spread (mm)
T3a T3b T3c T3d
o1.00 1.01–5.00 5.01–15.00 415.00
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examination; however MRI can provide accurate description of the tumour in relation to the anal verge and to other important components of the pelvis such as the levators and peritoneal reflection. For low rectal tumours, those which extend into the intersphincteric plane are most likely to lead to local recurrence and would most benefit from neo-adjuvant therapy. This can be identified pre-operatively on MRI.18 EAUS is not as accurate when describing low tumours, however this relates more to the additional staging information. The benefit of MRI over EAUS and rigid sigmoidoscopy lies in its ability to describe the extent of the tumour, not just the height of the tumour edge. This information greatly helps the surgeon plan the most appropriate operation.
9. Extramural venous invasion
Fig. 5. The tumour is penetrating into the surrounding mesorectum. The extent of spread in this image is more than 5 mm which is a poor prognostic marker.
increases to 85% and 97%, respectively.15 Figure 6 shows a malignant node on MRI. EUAS has a sensitivity and specificity for detection of cancerous lymph nodes in rectal cancer of 73% and 75%,16 respectively and is more likely to be accurate in more proximal rectum. It also has great difficulty in identifying nodes which are less than 5 mm in size. EAUS cannot interrogate the entire mesorectum and therefore cannot assess the lymph node status in the areas of the mesorectum it does not visualise. This may lead to under-staging of disease.
8. Height of tumour Defining the height of tumour is an important factor when considering the most appropriate form of surgical treatment, and in some cases, deciding on whether CRT may help in performing a less radical operation—will the patient need an anterior resection, abdominoperineal resection, defunctioning stoma, an extralevator operation? Tumours defined as “low rectal cancer” are within 5 cm of the anal verge and are more likely to lead to local recurrence.17 Tradition would lead us to believe that tumour height is best measured on rigid sigmoidoscopy or with a finger on rectal
Fig. 6. A malignant node on MRI.
Extramural vascular invasion (EMVI) is defined as the presence of malignant cells in the vasculature beyond the muscularis propria surrounding the tumour. It is known to be a stageindependent factor of poor prognosis in rectal cancer19 and is associated with an increased risk of local recurrence and distant metastases.20 The presence of EMVI in colorectal cancer is seen in as much as 50% of tumours but is almost always associated with more advanced stage—T3 and T4 tumours.21 Patients with EMVI as a feature of the tumour have a 50% chance of developing metastases compared with 12% in EMVI negative patients. Yet there is relatively little known about this phenomenon. It is almost exclusively seen in T3 and T4 tumours and may be the natural progression of intramural vascular spread. EAUS has no effective ability to distinguish normal vessels from those which have been infiltrated with tumour. MRI shows a characteristic serpiginous extension of tumour signal into perirectal fat.22 The fact that this is only seen in T3 and T4 tumours is understandable as a tumour which is limited to muscularis propria will be unlikely to have tumour spread into extramural veins. This is shown in Figure 7. Assessment of EMVI using MRI must consider the following components: pattern of tumour margin which gives the appearance of nodularity; location of tumour to relevant vessels which makes tumour invasion more likely; calibre of vessel as tumour infiltration can cause an increase in luminal size; and vessel border if the tumour disrupts the vessel itself.23 Table 3 shows the EMVI classification based on MRI appearance.
Fig. 7. The sagittal section shows tumour penetrating into the extramural vasculature beyond the muscularis (white arrow).
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References
Table 3 EMVI classification. MRI-EMVI score
EMVI status
Description
0 1 2
Negative Negative Negative
3 4
Positive Positive
No vessels adjacent to areas of tumour penetration Minimal stranding but well away from vessels Stranding within vicinity of vessel but no definite tumour signal Intermediate signal within slightly expanded vessel Irregular contour of vessel by definite tumour signal
10. Clinical considerations of MRI or EAUS MRI has become the imaging modality of choice in the UK and Europe but is not so popular in the US. This may be partly explained by the differing approaches to neo-adjuvant treatment. MRI has the advantage of recognising the adverse features which make a tumour “high-risk” and therefore more likely to benefit from neo-adjuvant treatment. This means that patients are selected on the basis of highrisk features identified on imaging as much of this information is lacking from biopsy material. The perceived advantage of being more selective is that patients may not have to undergone additional treatments with little benefit. Both techniques have their advantages however these must be appreciated in terms of clinical approach. Certainly, a more tailored approach would allow the use of the most appropriate technique for any given situation. In the past, any T3 would have been considered for neoadjuvant therapy. However on more detailed analysis of imaging and outcomes this results in overtreatment to the detriment of sphincter function and anastomotic healing. It is therefore logical to consider this risk in terms of recurrence—those tumours which are involving the CRM but without other adverse features; patients who are at risk of distant recurrence but would not benefit from local radiotherapy as much as systemic treatment; and finally those who are at risk of both types of recurrence who need the most aggressive pre-operative strategy. 11. Conclusion MRI and EAUS are individually advantageous in the local staging of rectal cancer. MRI is an overall better imaging modality as it is able to provide accurate detail on the tumour spread as well as the relationship to important features within the pelvis. EAUS is particularly useful for early tumours and the planning of local resection procedures. The decision as to which modality to use depends on the treatment policy with regards to oncological therapy. For a more selective approach where patients with high-risk tumours are offered neo-adjuvant treatment, MRI is a superior imaging tool. However this comes against increased cost and user expertise.
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