MR imaging strides ahead in rectal cancer staging

November 1, 2006

In rectal cancer, mortality rates are high and prognoses are generally poor, owing to the strong risk of metastases and local recurrence.

In rectal cancer, mortality rates are high and prognoses are generally poor, owing to the strong risk of metastases and local recurrence. The standard surgical treatment for cancer located in the middle and lower sections of the rectum is total mesorectal excision; that is, resection of the tumor together with the surrounding mesorectal fat.1 This procedure is associated with a recurrence rate of less than 10% when used on its own.2 Although local recurrence has a small effect on survival rate, it has a profound influence on a patient's quality of life, given that rectal cancer is difficult to treat and causes disabling symptoms.3

Accurate preoperative imaging can improve the quality of care for patients with rectal cancer. Accurate tumor staging is central to prognosis and preoperative treatment planning, but clinical examination is insufficient.4 Radiological assessment for local tumor staging has consequently assumed a prominent role in the management of patients with rectal neoplasia.

Presurgical staging is aimed at assessing the resectability of neoplasms, while minimizing the risk of local recurrence. Preoperative staging techniques should also identify patients with extrarectal spread, who might benefit from preoperative radiotherapy, and patients with minimal or no sphincter involvement, who might be suitable for sphincter-sparing surgery.5

It is essential to stratify patients clinically into those with tumors that can be locally excised (usually reserved for T1 cancers) and those with deeper tumors that will need total mesorectal excision.6-9 Some patients will also need a long course of preoperative radiation therapy in an attempt to downstage T4 tumors.10

Transrectal ultrasound has been used to stage rectal cancer for many years, thanks to its ability to visualize the different layers of the rectal wall with high spatial resolution. The modality can crucially define superficial tumors confined within mucosa and submucosa that are potentially suitable for cure by local excision. The small field-of-view, however, means that it offers limited evaluation of stenosing lesions and tumors located at the rectosigmoid junction. Neither can it identify mesorectal fascia and lymph nodes far from the rectal wall. Transrectal ultrasound is thus not useful for staging advanced rectal cancer.11

The accuracy of CT for local staging of rectal cancer is still likely to be poor, despite the advent of multislice technology. This is due to low contrast resolution and the inability to reliably depict tumor parietal infiltration.

MRI OPTIONS

MRI is emerging as a problem-solving technique that can define therapeutic planning of rectal carcinoma. Imaging is conducted with either an endorectal coil or a phased-array surface coil. Protocols for patient preparation, pulse sequences, and plane acquisition are independent of coil type.

Studies comparing endorectal MRI and transrectal ultrasound for staging superficial tumors have shown the two techniques to have comparable accuracy.12,13 Endorectal MRI provides high-resolution images that depict bowel wall layers fully, although clear differentiation between mucosa and submucosa is still difficult. Evaluation of stenosing carcinomas can be tricky, however. Coil insertion can be problematic, painful, and sometimes impossible in cases of high-grade strictures, leading to insertion failure rates as high as 40%.14 Reports have also mentioned poor resolution of pelvic structures surrounding the rectum, such as mesorectal fat, mesorectal fascia, and lymph nodes outside the field-of-view.15

Use of a phased-array coil provides images with high spatial resolution over a large field-of-view. Stenosing lesions and tumors at the rectosigmoid junction can be evaluated in all cases, and mesorectal fat and the mesorectal fascia can be visualized. Patient discomfort is reduced considerably.

An imaging protocol for MR-based staging of rectal cancer should yield high-resolution T2-weighted images in three orthogonal planes. These can be obtained with a non-breath-hold turbo spin-echo sequence with the following parameters: 4300 msec TR; 132 msec effective TE; 33 echo train length; 420 x 512 matrix; 28 cm field-of-view; 3 mm section thickness; 0.54 mm x 0.54 mm in-plane resolution. Fat-suppressed T2-weighted imaging has been advocated to improve visualization of tumor spread within perirectal fat. The use of contrast-enhanced T1-weighted sequences (spin-echo or gradient-echo) is still being debated.

Three different layers of the rectal wall can be recognized on T2-weighted MRI. These are an inner hyperintense layer representing mucosa and submucosa (no differentiation is possible between these two anatomic entities), a hypointense intermediate layer representing the muscularis propria, and an external hyperintense layer representing perirectal fat tissue. The mesorectal fascia can also be identified as a fine low-intensity structure enveloping the mesorectum and surrounding perirectal fat tissue. The mesorectal fascia is clearly visible on the lateral and posterior views, but it is difficult to differentiate from Denonvillier's fascia in the anterior view.

PRESURGICAL QUESTIONS

Local staging of rectal cancer is determined by the tumor's relationship to the rectal wall (assessed by T-stage classification) and to mesorectal fascia (assessed by the circumferential resection margin). TNM (tumor, nodes, metastases) staging remains an important method of predicting survival. The presence of poor prognostic indicators within each TNM stage means that patient subgroups of differing risk can be identified and treated accordingly.

The real aim of presurgical staging is to identify patients who will be suitable for additional treatment and may consequently have a better outcome. The circumferential resection margin (CRM) is one of the strongest predictors of surgical failure and a marker of the quality of surgical resection. While CRM is not yet included in current TNM staging, there is strong evidence that the neoplastic involvement of CRM is strictly related to a high recurrence rate after surgical treatment.16

MRI performed with a phased-array coil consistently permits accurate assessment of the depth of extramural tumor spread and determination of mesorectum involvement. It can also reveal any infiltration of perirectal fat, show whether the lateral resection margin can be predicted, and indicate the extent of any sphincteral involvement.17

The feature that helps most in clinical decision-making is the prediction of tumor margin relative to mesorectal fascia. Both T3 lesions and T2 lesions (Figure 1) require total mesorectal excision on surgery. MRI with a phased-array coil can predict the lateral resection margin with great accuracy. This enables appropriate selection of patients for preoperative radiotherapy and avoids unnecessary treatment of patients with a wide tumor-free lateral resection margin (Figures 2 and 3).

Information about sphincter involvement is one of the most important features influencing treatment selection. Such involvement can be predicted with a high degree of certainty using phased-array MRI. The technique provides excellent visualization of the sphincteral complex on coronal images (Figure 4). It is also a valuable tool to exclude or prove external and internal sphincteral infiltration. Phased-array MRI can additionally identify tumors involving adjacent organs. Such tumors will be candidates for preoperative radiotherapy as a downstaging strategy prior to radical tumor resection.

Identification of nodal disease continues to be a problem for radiologists. Lymph nodes measuring just 2 to 3 mm can be identified on images with high spatial resolution. But nodal metastases are not always reliably detected. Characterization and size criteria for enlarged lymph nodes also lack consensus. Some authors report any detectable lymph node, while others just report nodes larger than 3 mm, 5 mm, or 10 mm.18,19 The problems for morphologic imaging are to distinguish between enlarged reactive and metastatic nodes, and to detect micrometastases.

Ultrasmall superparamagnetic iron-oxide particles (USPIO) promise to make a real improvement in lymph node characterization. These particles are selectively taken up by reticuloendothelial cells of normal lymph nodes, presenting as a dark signal on proton- density and T2-weighted MRI. Pathologic lymph nodes, where reticuloendothelial cells are replaced by neoplastic cells, will not take up the USPIO contrast and present with relatively bright signal. Preliminary results using such agents are promising.20 Further larger studies are now needed to assess their real diagnostic value.

LOCAL RECURRENCE

Between 60% and 84% of all tumor recurrences are detected within 24 months of major resection, and 90% to 93% within 48 months.21,22 Risk factors for local recurrence include tumor stage, tumor grade, distance from anal verge, presence of lymphovascular invasion, anastomotic leak, and tumor perforation during resection. The presence of tumor at the circumferential resection margin is another major risk factor.

A crucial challenge in the follow-up of patients with suspected local recurrence from rectal cancer is differentiation between early tumor recurrences and post-therapeutic alterations. CT has a reported specificity of 69% to 72% and a sensitivity of 82% to 91% for the detection of local pelvic recurrence. MRI has limitations similar to those of CT in the detection of local pelvic recurrence, predominantly based on morphological changes. It was initially thought that increased signal intensity on T2-weighted MRI would help differentiate fibrosis from recurrent tumor. High T2 signal, however, may persist for up to two years after surgery, making interpretation difficult. Conventional contrast-enhanced imaging is also limited in this regard. Benign fibrotic scarring, malignant local tumor recurrence, and inflammation can all enhance following gadolinium administration.

MRI appears to be superior to CT for the detection of local tumor recurrence.23 Sensitivity is between 80% and 90%, and specificity can be as high as 100%. Dynamic enhancement techniques have also generated some interest, given that local tumor recurrence enhances earlier than benign disease.24,25

MRI with a phased-array coil allows excellent visualization of the pelvic structures and will also evaluate the spatial distribution of rectal cancer well. It can predict involvement of both perirectal tissue and anal sphincters reliably, enabling appropriate selection of patients for pre-operative radiotherapy or sphincter-saving surgery.

DR. IAFRATE is a radiologist and research fellow, and DR. LAGHI is an associate professor and director of the CT and MR unit, both in the department of radiological sciences at the University of Rome La Sapienza in Italy.

References1. Peschaud F, Cuenod CA, Benoist S, et al. Accuracy of magnetic resonance imaging in rectal cancer depends on location of the tumor. Dis Colon Rectum 2005;48(8):1603-1609.
2. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. NEJM 2001;345(9):638-646.
3. Wiggers T, de Vries MR, Veeze-Kuypers B. Surgery for local recurrence of rectal carcinoma. Dis Colon Rectum 1996;39(3):323-328.
4. Beets-Tan RG, Lettinga T, Beets GL. Preoperative imaging of rectal cancer and its impact on surgical performance and treatment outcome. Eur J Surg Oncol 2005;31(6):681-688.
5. Iafrate F, Laghi A, Paolantonio P, et al. Preoperative staging of rectal cancer with MRI: correlation with surgical and histopathological results. Radiographics 2006;26(3):701-714.
6. Akasu T, Kondo H, Moriya Y, et al. Endorectal ultrasonography and treatment of early stage rectal cancer. World J Surg 2000;24(9):1061-1068.
7. Gao JD, Shao YF, Bi JJ, et al. Local excision carcinoma in early stage. World J Gastroenterol 2003;9(4):871-873.
8. Langer C, Liersch T, Markus P, et al. Transanal endoscopic microsurgery (TEM) for minimally invasive resection of rectal adenomas and "low-risk" carcinomas (uT1, G1-2). Z Gastroenterol 2002;40(2):67-72.
9. Brown G. Local radiological staging of rectal cancer. Clin Radiol 2004;59(3):213-214.
10. Kaminsky-Forrett MC, Conroy T, Luporsi E, et al. Prognostic implications of downstaging following preoperative radiation therapy for operable T3-T4 rectal cancer. Int J Radiat Oncol Biol Phys 1998;42(5):935-941.
11. Laghi A, Ferri M, Catalano C, et al. Local staging of rectal cancer using a phased array body coil. Abdom Imaging 2002;27(4):425-431.
12. Beets Tan RG, Beets G. Rectal cancer: Review with emphasis on MR imaging. Radiology 2004;232(2):335-346.
13. Gualdi GF, Casciani E, Guadalaxara A, et al. Local staging of rectal cancer with transrectal ultrasound and endorectal magnetic resonance imaging: comparison with histologic findings. Dis Colon Rectum 2000;43(3):338-345.
14. Joosten FB, Jansen JB, Joosten HJ, et al. Staging of rectal carcinoma using MR double surface coil, MR endorectal coil, and intrarectal ultrasound: correlation with histopathologic findings. JCAT 1995;19(5):752-758.
15. Shellito PC, Clark JW, Willett CG, Caplan AP. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 18-2004. A 61-year-old man with rectal bleeding and a 2-cm mass in the rectum. NEJM 2004;350(24):2500-2509.
16. Brown G, Davies S, Williams GT, et al. Effectiveness of preoperative staging in rectal cancer: digital rectal examination, endoluminal ultrasound or magnetic resonance imaging? Br J Can 2004;91(1):23-29.
17. Ferri M, Laghi A, Mingazzini P, et al. Preoperative assessment of extramural invasion and sphincteral involvement of rectal cancer by MRI with phased array coil. Colorectal Disease 2005;7(4):387-393.
18. Kim JH, Beets GL, Kim MJ, et al. High resolution MR imaging for nodal staging in rectal cancer: are there any criteria in addition to the size? Europ J Radiol 2004;52(1):78-83.
19. Brown G, Richards CJ, Bourne MW, 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.
20. Koh DM, Brown G, Temple L, et al. Rectal cancer: mesorectal lymph nodes at MR imaging with USPIO versus histopathologic findings-initial observations. Radiology 2004 Apr;231(1):91-99.
21. Thompson WM, Halvorsen RA, Foster Jr. WL, et al. Preoperative and postoperative CT staging of rectosigmoid carcinoma. AJR 1986;146(4):703-710.
22. Tan PL, Chan CL, Moore NR. Radiological appearances in the pelvis following rectal cancer surgery. Clin Radiol 2005;60(8):846-855.
23. Blomqvist L, Ohlsen H, Hindmarsh T, et al. Local recurrence of rectal cancer: MR imaging before and after oral superparamagnetic particles vs contrast-enhanced computed tomography. Europ Radiol 2000;10(9):1383-1389.
24. Kinkel K, Tardivon AA, Soyer P, et al., Dynamic contrast-enhanced subtraction versus T2-weighted spin-echo MR imaging in the follow-up of colorectal neoplasm: a prospective study of 41 patients. Radiology 1996;200(2):453-458.
25. Muller-Schimpfle M, Brix G, Layer G, et al., Recurrent rectal cancer: diagnosis with dynamic MR imaging. Radiology 1993;189(3):881-889.