Endorectal ultrasonography is an established staging modality in patients with rectal tumors.7,8 A meta-analysis showed a pooled sensitivity and specificity for ERUS staging of 94% and 86% in the setting of tumor ingrowth into the bowel wall, 90% and 75% for perirectal tissue invasion, and 70% and 97% for organ invasion, respectively.9 The agreement between uT-stage and pT-stage in the larger studies is 65% to 70%, with 10% to 15% understaging and 20% overstaging.10-12 ERUS can discriminate between mucosal pT0 lesions and pT1 tumors, with a risk of understaging for uT0 of only 5% to 15%.12-16 In uT1 there is understaging in 15% to 20%, and in uT2 stage 15% to 30%, while overstaging in uT3 occurs in 25% to 30%. ERUS is accurate in assessing tumor invasion into organs such as the vagina, uterus, prostate, and seminal vesicles, especially in tumors that are within reach of the probe. ERUS is less suitable for evaluating tumor involvement of the mesorectal fascia (MRF), a structure that is not well recognized by ERUS. Moreover, ERUS provides only a limited view of the extent of tumor and its relation to the surrounding pelvic structures—especially in those areas outside the scope of the probe. Although ERUS is less suitable for depicting the exact tumor extent in larger tumors, it remains the method of choice for staging superficial cT1 rectal cancers because it is the only imaging technique that can visualize the individual layers of the bowel wall (Fig. 107-1).
Endorectal ultrasonography of a patient with cT1 rectal cancer. The tumor (white asterisk) invades the hyperechoic submucosal layer (white arrow), but does not invade the hypoechoic muscular bowel wall (white arrow head). ERUS visualizes all individual layers of the bowel wall. Therefore, ERUS remains the first method of choice for staging superficial (cT1) tumors.
Although CT is superior to ERUS and, because of its wider field of view, more accurately assesses tumor extension into the pelvic structures, CT is not as accurate as MRI because of its inferior contrast resolution. Bipat and coworkers pooled the data of CT studies published between 1985 and 2002, reporting a pooled sensitivity and specificity of 79% and 78 %, respectively, in the setting of perirectal tissue invasion, and 72% and 96 %, respectively, for organ invasion.9
International guidelines increasingly incorporate MRI as part of the standard workup of patients with rectal cancer.17,18 A meta-analysis of MRI studies published between 1993 and 2002 reported a pooled sensitivity and specificity of 94% and 69%, respectively, in the staging of cT2; 82 and 76%, respectively, for cT3 and 74; and 96% for cT4 tumors.9 Most staging failures with MR imaging occurred in differentiating between T1 and T2 lesions, and T2 and T3 lesions. On MRI, a T1 tumor cannot be reliably distinguished from a T2 because the submucosal layer is generally not visualized. Like ERUS, MRI cannot distinguish between some borderline cT2-cT3 lesions, especially when there are spiculated desmoplastic extensions of the tumor in the surrounding mesorectal fat tissue (Fig. 107-2a, b). In these borderline lesions the exact T stage may, however, be clinically less relevant, as the depth of ingrowth into the mesorectum has been shown to be an independent prognostic variable, with an early T3 lesion behaving more like a T2 lesion.19 This has been confirmed in other studies, and a subdivision of T3 tumors—according to depth of tumor ingrowth into the mesorectum—has been recommended in the TNM Supplement of the International Union Against Cancer (UICC).20 A large European multicenter study showed that MRI is very accurate in predicting this extramural ingrowth, and can be used to select a prognostically good group of tumors with up to 5 mm of ingrowth.21,22
MR images of a male patient with pT2 rectal tumor (A) and a male patient with a pT3 rectal tumor (B). In both patients the dark bowel wall cannot be clearly delineated at the circumference of the tumor (black arrows). Instead subtle desmoplastic stranding is shown. The MR image of a pT2 rectal cancer with desmoplastic stranding into the mesorectal fat mimics that of a pT3a-b rectal tumor with desmoplastic reaction. Overstaging errors are known to occur in 30% to 40% of these borderline tumors.
MESORECTAL RESECTION MARGIN
The lateral or radial resection margin of a TME procedure is just outside the MRF. A positive CRM can thus be the result of inadequate TME surgery, or an advanced tumor that comes close to or invades the MRF. Preoperative identification of patients with a threatened or involved MRF identifies tumors at high risk for a local recurrence; these patients are generally treated with a long course of chemoradiation followed by a long interval prior to surgery to provide optimal tumor downsizing. It is also relevant for the surgeon to know the exact relation of the tumor to the surrounding pelvic structures and MRF in order to obtain a complete resection.
The role of helical multislice CT (MSCT) for the assessment of the MRF has been studied in a prospective multicenter study.23 For mid and high rectal tumors CT is reasonably good in ruling out an involved MRF with a sensitivity of 76% and a specificity of 96%. For low rectal cancer this is more difficult, because low in the pelvis the structures are close to each other with little or no interposed fatty tissue. CT has inherently less contrast resolution than MRI, which in these low tumors leads to a sensitivity of only 66% and a specificity of 82% for the involvement of the MRF.
At present, because of the inherently high tissue contrast and high spatial resolution of modern MR equipment, MRI is the best imaging method for providing detailed information on the relation between tumor and surrounding structures. This detailed anatomical information can serve as a road map for surgery, and it is often said that, with MRI, “what you see is what you get” (Fig. 107-3).
MRI of a male patient with a locally advanced low rectal cancer. The relation between the tumor and surrounding normal structures is well appreciated on MRI because of the inherent high tissue contrast. Anteriorly the tumor is threatening the prostate (white arrow) and this organ is at risk for tumoral invasion. Laterally the tumor is invading the mesorectal resection margin and threatens the pelvic floor muscles (black arrows). MRI serves as an excellent road map before surgery. It is often said that with MRI "what you see is what you get."
An involved MRF on MRI is defined as a closest distance of ≤1 mm between tumor and resection margin, as this represents the optimal prognostic cut-off point. Many single-center studies have shown that MRI is highly accurate in the assessment of an involved MRF (Fig. 107-4).24,25 The results of a systematic review confirm the high performance of MRI, showing a sensitivity in assessing an involved MRF of 60% to 88%, and a specificity of 73% to 100%.26 The subsequent European multicenter study showed a sensitivity of 59%, specificity of 92%, PPV of 54%, and NPV of 94%.27 When MR findings are incorporated into the multidisciplinary decision-making process of rectal cancer treatment, a decrease in the number of positive margins was found.28 A recently published multicenter cohort study showed that differentiated treatment of primary rectal cancer based on MRI can result in a proportion of complete resections as high as 96% (218 out of 228 included patients) and can reduce—at a median follow-up of 41 months—the 3-year local recurrence rate to as low as 2.2%.29
MRI of a male patient with a locally advanced low rectal cancer. Anteriorly on the right the tumor extends to the mesorectal fascia and probably invades it (white arrow). An extramesorectal node is visualized with morphological features suggesting an involved node (black arrow).
An important risk factor for both local and distant recurrence is the presence of lymph node metastases, and this is generally considered an indication for neoadjuvant radiotherapy.17 Identifying nodal disease with imaging remains difficult, however, because the use of size criteria alone as a measure of metastases results in only moderate accuracy. Lymph nodes with a diameter of >8 mm are invariably malignant. However, many of the involved lymph nodes in rectal cancer are smaller than 5 mm.30 Additional morphological criteria have been proposed, such as round shape, an irregular border, and heterogenous texture indicating malignancy (Fig. 107-5). In two meta-analyses, ERUS performed slightly better than CT or conventional MRI, most likely due to the additional inclusion of these morphological criteria in the ERUS studies.9,26 The pooled sensitivity and specificity for nodal involvement was 67% and 78% for ERUS, 55% and 74% for CT, and 66% and 76% for MRI. A more recent meta-analysis of MRI showed accuracy in the same range: sensitivity of 77% and specificity of 71%.25 An advantage of MRI over ERUS is the wider field of view, which can visualize nodes high in mesorectum, along the superior rectal vessels—an area beyond the scope of the endosonography probe. The moderate accuracy of nodal staging was illustrated in a study by Guillem et al reporting on a group of cT3N0 tumors, staged by ERUS (69%) or MRI (31%), that were subsequently treated with CRT and surgery:31 on histology, node-positive disease was observed in as many as 22% of the tumors!
MRI of a male patient with a low rectal cancer and suspicious mesorectal nodes. The tumor is shown in the low rectum. Because the dark muscular bowel wall is well delineated at the level of the tumor (black arrow), it is likely that the tumor is limited to the bowel wall (cT2). In the dorsal mesorectum at level S1–3 nodes are visualized with at least two out of three morphological MR features of malignancy: round shape, irregular border, and heterogenous texture (white arrows).
However, others have confirmed that the addition of morphological criteria to size can improve the accuracy of MRI in detecting nodal metastases.32 These morphological features are well appreciated if the nodes are large, but more difficult to define in smaller nodes, as these features may remain beyond the resolution of even high-resolution MR technology. A recent consensus meeting of 14 rectal cancer imaging specialists from the European Society of Gastrointestinal and Abdominal Radiology stated that although size thresholds of 5 to 8 mm were common in clinical practice, “no single diameter threshold is sufficiently accurate to differentiate benign from malignant nodes, and … the choice of a threshold is contingent upon the desired balance between sensitivity and specificity, which varies per clinical setting.”18 So, how does one work with this in clinical practice? When no nodes are visible on MRI, it is safe to call it N0 disease. When a node is larger than 8 mm, it should be considered malignant. For the smaller nodes our center uses the following (somewhat arbitrary) guideline: nodes of 5 to 8 mm are considered suspicious when at least two of the morphological criteria are present (round shape, irregular border, or heterogenous texture of the node); nodes <5 mm are deemed suspicious only when all three criteria are present. Although this strategy will miss some small involved nodes, it avoids overcalling and overtreating many node-negative tumors.
MR techniques and sequences are improving, and with modern contrast-enhanced technology the accuracy of lymph node staging is likely to improve. One such contrast agent is ultrasmall superparamagnetic particles of iron oxide (USPIO). This has been tested for the prediction of rectal cancer nodal status in a multicenter study, showing a higher sensitivity and specificity of around 80% to 90%.33 (It has not been FDA- or EMEA-approved, and is not available for clinical practice.) Another promising MR nodal contrast agent is gadofosveset, which in a recent study showed higher accuracy rates than MR without contrast.34,35 (This contrast agent is not yet available for clinical practice, and is registered only for use in vascular imaging.)
At present, lymph node staging with imaging is only moderately accurate, mainly because of the difficulty in detecting small-volume nodal disease. Some studies suggest that small-volume nodal disease is a less important factor in local recurrence than high-volume nodal disease, and can be controlled by high-quality TME surgery without neoadjuvant therapy.22,36 This, however, requires further confirmation.
EXTRAMURAL VENOUS INVASION
Extramural venous invasion is histologically characterized by the presence of tumor cells in large veins in the mesorectum. This is an additional and independent poor prognostic risk factor in colorectal cancer.37 EMVI in rectal cancer can be detected on MRI, and Smith et al suggest a five-point (0–4) MR scale system in which three or higher assigned points correspond with EMVI + histology38 (Fig. 107-6). Neoadjuvant therapy is generally indicated when EMVI is suspected on MRI.
MRI of a male patient with locally advanced rectal cancer. A mid to high rectal cancer is visualized with anterior invasion of the peritoneal reflection (white arrowhead) and posterior nodular tumoral extension into the mesorectal fat and invasion of a vein, indicating a tumor with extramural venous invasion (white arrow). Extramural venous tumor invasion in rectal cancer is known as a poor prognostic risk factor and neoadjuvant therapy is generally indicated when EMVI is suspected on MRI.