Staging of endometrial cancer with MRI: Guidelines of the European Society of Urogenital Imaging
- 1.6k Downloads
The purpose of this study was to define guidelines for endometrial cancer staging with MRI. The technique included critical review and expert consensus of MRI protocols by the female imaging subcommittee of the European Society of Urogenital Radiology, from ten European institutions, and published literature between 1999 and 2008. The results indicated that high field MRI should include at least two T2-weighted sequences in sagittal, axial oblique or coronal oblique orientation (short and long axis of the uterine body) of the pelvic content. High-resolution post-contrast images acquired at 2 min ± 30 s after intravenous contrast injection are suggested to be optimal for the diagnosis of myometrial invasion. If cervical invasion is suspected, additional slice orientation perpendicular to the axis of the endocervical channel is recommended. Due to the limited sensitivity of MRI to detect lymph node metastasis without lymph node-specific contrast agents, retroperitoneal lymph node screening with pre-contrast sequences up to the level of the kidneys is optional. The likelihood of lymph node invasion and the need for staging lymphadenectomy are also indicated by high-grade histology at endometrial tissue sampling and by deep myometrial or cervical invasion detected by MRI. In conclusion, expert consensus and literature review lead to an optimized MRI protocol to stage endometrial cancer.
KeywordsUterus, endometrium Uterine neoplasms, staging, uterine neoplasms Magnetic resonance (MR), gynecologic oncology
Endometrial cancer is the fourth most frequent cancer in women and now the most common gynecological cancer in many developed countries . Surgical treatment options depend on the local extent of disease [2, 3]. In low-risk patients only hysterectomy with bilateral oophorectomy is performed, whereas in selected high-risk patients lymphadenectomy, omental and peritoneal biopsies are included in the surgical treatment . The most recent surgical trend consists in performing lymphadenectomy through laparoscopy . The disadvantage of systematic lymphadenectomy is a 7–10% risk of lymph cyst formation after surgery [5, 6], increased anesthesia and operating time, and the need for a specialized oncologic surgeon. However, when lymphadenectomy is not performed, most patients will undergo either a second surgery with pelvic lymphadenectomy when pathology of the uterus reports deep myometrial or cervical invasion, or a systematic pelvic or intravaginal postoperative radiation therapy. Pelvic radiation therapy might not be necessary if prior lymphadenectomy has not shown lymph node invasion . Patient selection for primary lymphadenectomy at the time of hysterectomy is therefore a current debate in oncological gynecology .
In patients with endometrial cancer, histological tumor grade and depth of myometrial invasion strongly correlate with lymph node metastases and patient survival . Therefore, patients are considered at high risk for lymph node invasion when high tumor grade is diagnosed at endometrial biopsy or when deep myometrial invasion is identified before surgery. A meta-analysis of reported MRI studies suggests that preoperative identification of deep myometrial invasion in patients with endometrial cancer is best performed with contrast-enhanced MRI of the pelvis with an accuracy of about 91% . Without the use of contrast-enhanced MRI and using only the knowledge of preoperative tumor grade from the endometrial biopsy, the probability of deep endometrial invasion has been estimated at respectively 13% for tumor grade 1, 35% for tumor grade 2 and 54% for tumor grade 3 . After a positive MRI for deep myometrial invasion, those probabilities change to respectively 60, 84 and 92% for tumor grade 1, 2 and 3. When MRI of the pelvis does not identify deep myometrial invasion, the probability of such a condition decreases to respectively 1, 5 and 10% for tumor grade 1, 2 and 3 . However pitfalls in diagnosing the extent of endometrial cancer have been reported with MRI when associated adenomyosis or large leiomyoma impairs exact assessment of the depth of myometrial invasion [11, 12]. To reduce potential pitfalls or misinterpretation of false-negative or false-positive findings of myometrial or cervical invasion, MRI images should be acquired with enough technical quality to allow adequate image interpretation. Many of the studies analyzed in the meta-analysis  were small series reported from the proving stage of MRI, and some revealed low image quality and a lack of technical standards. Thus, the female pelvis subcommittee of the European Society of Urogenital Imaging (ESUR) formed a working group to establish technical guidelines for endometrial cancer staging with MRI based on extended clinical practice.
Material and methods
MRI protocols for staging endometrial cancer were collected from ten European institutions. Inclusion criteria to participate in the guidelines topic “Staging endometrial cancer with MRI” were: to be a member of the European Society of Urogenital Imaging (ESUR) and to perform at least ten MR imaging examinations per year for staging biopsy-proven endometrial carcinoma. The questionnaire included the following details: field strength and type of coil, patient preparation, type of sequence with detailed geometry and contrast information, such as FOV, matrix scan and reconstruction, slice thickness, gap, orientation, saturation bands, 2D versus 3D sequence, TR/TE, number of acquisitions, number and lengths of dynamic sequences, bolus IV injection and use of subtraction techniques. In addition, published literature between 1999 and 2008 was reviewed through a Medline literature search of abstracts in the English language on studies in human subjects, including the following key words: “Uterine neoplasm(s) AND MR imaging” or “Endometrial carcinoma AND MR imaging.” Articles that did not include technical details following the information of the questionnaire were excluded. The results were presented in an excel sheet including descriptive statistics, and were discussed and divided in topics with agreement and disagreement. Topics with disagreement were conpared to the literature. Experts in favor of one technical option were asked to document their point of view with the corresponding literature, which was discussed by an expert panel. Literature work was compared taking into consideration year of publication, number of cases and performance of the technique. When technical details varied and no published work on performance was found, the subject was discussed and resolved in consensus based on the majority of participating members. Members of the group met twice a year during a 2-year period and were asked to apply technical recommendations issued after the first two meetings during year 1 before the meetings in year 2 to allow further discussion and making final conclusions in consensus.
Technical consideration with agreement
Results of the literature search according to year of publication
Eur J Gynaecol Oncol
Int J Gynecol Cancer
Discordance concerning dynamic post-contrast sequences
A single discordant topic concerned the type of contrast-enhanced T1-weighted sequences: 2D versus 3D sequence, a single or up to eight dynamic acquisitions after intravenous contrast medium, as well as the length of a single dynamic acquisition that varied between 18 s and 3 min 21 s. Dynamic image acquisition has been recommended since Yamashita et al. in 1993, observing less contrast between the tumor and the normal myometrium at 5 min after injection of contrast agent compared to 2 min after injection . The authors demonstrated that at dynamic imaging acquired every 30 s, normal myometrium showed strong early enhancement at 90 s after bolus enhancement, particularly at the junctional zone. The tumor invading the myometrium demonstrated decreased enhancement compared to the strong enhancement of normal myometrium. The greatest contrast between invaded and non-invaded myometrium was visible at 2 min after injection. Most publications after 1993 therefore presented imaging protocols with dynamic enhancement. In 2004, Manfredi et al. demonstrated an optimal contrast-to-noise ratio between the endometrial tumor and the normal myometrium at 2 min 30 s compared to 30 s and 1 min 30 s after intravenous injection of contrast agent . The imaging protocol used a dynamic 3D gradient echo sequence (FMSPGR) with one unenhanced and three enhanced acquisitions of 1-min acquisition time each. A quantitative analysis of the contrast-to-noise ratio between the endometrial tumor and the normal myometrium was performed through a region-of-interest analysis at a workstation.
Suggested MR imaging protocol for staging endometrial cancer
Patient preparation and positioning:
Fasting: 3–6 h
Antiperistaltic agent if not contraindicated
Pelvic phased-array coil
Image orientation: Sagittal, axial oblique (perpendicular) and coronal oblique (parallel) to the uterine cavity. If cervical involvement is suspected, additional axial oblique image orientation perpendicular to the long axis of the endocervical channel
Slice thickness for the pelvis: ≤4 mm, FOV 20–25 cm. High-resolution matrix (512 × 512)
Extended FOV for assessing the retroperitoneum with coronal T1-weighted or axial T2-weighted sequence with fat suppression
Suggested for higher accuracy of the diagnosis of deep myometrial invasion. Recommended for atrophic uteri, associate adenomyosis or fibroids, or in suspected advanced tumors (suspicious bladder or rectal wall invasion)
2D or 3D techniques may be performed with the optimal tumor/myometrial contrast timing between 90 and 150 s. A single 3D acquisition technique seems a good alternative to dynamic imaging as it combines a high tumor-myometrium contrast with multiplanar reformations and thin slice sections
Criteria for image interpretation according to tumor stage
The MR staging criteria for endometrial cancer follows the guidelines of the surgically-pathologically based FIGO classification [26, 37]. Stage O tumors (carcinoma in situ) are not visualized on MRI. In stage I endometrial cancer, the tumor is limited to the uterine corpus. It encompasses tumor without myometrial invasion (stage IA), superficially (IB) and deeply (IC) invasive cancers of the myometrium. In stage IA normal, diffusely or focally thickened endometrium larger than 3 mm in postmenopausal age may be seen. The key feature in imaging is identification of the intact low signal intensity junctional zone at T2-weighted imaging. At T1-weighted dynamic imaging complete subendometrial enhancement may be visible. If the junctional zone is not visible, a sharp tumor-myometrial interface at T2-weighted imaging and at contrast-enhanced images suggests an intact myometrium. It is not unusual to see minimal abnormality, such as a small amount of fluid within the endometrial cavity after diagnostic resection.
Conversely, in stage IB and IC cancer myometrial invasion is found. In stage IB, which refers to myometrial invasion of less than half of the myometrial thickness, disruption or irregularity of the low signal intensity junctional zone by intermediate signal intensity mass is identified at T2-weighted imaging (Figs. 1 and 3). If the junctional zone is not visible, as in up to half of postmenopausal women or in associated findings, such as fibroids and adenomyosis, contrast-enhanced MRI helps in the assessment of the depth of myometrial invasion . In stage IB at approximately 2 min or 90 to 150 s at contrast-enhanced imaging, an irregular endometrium/myometrium interface is best identified . In stage IC the endometrial cancer extends into the outer half of the myometrium, but a small stripe of deep normal myometrium is preserved (Fig. 2).
In stage III tumor extends beyond the uterus, but is confined to the true pelvis. In stage IIIA transmyometrial involvement and disruption of the T2 hypointense uterine serosa and/or irregular uterine contour is noted. Other findings may include adnexal or parametrial involvement. Metastases to or direct extension to the upper vagina with focal loss of the low signal intensity vaginal wall is typical for stage IIIB. Pelvic and/or para-aortic lympadenopathy indicates stage IIIC. Imaging signs of lymph node involvement include a diameter equal to or greater than 8 mm in the pelvis or in round nodes and of greater than 10-mm short axis in retroperitoneal or oval nodes.
Stage IV endometrial cancer is defined by tumor extension beyond the true pelvis or involvement of the bladder or rectal mucosa. MRI findings include disruption of the low signal intensity of the bladder or rectal wall, a mucosal or intra-luminal mass (stage IVA) best identified with contrast-enhanced sequences. Distant metastases (IVB) are rare at presentation and better seen at CT or at an extended MR imaging protocol to the abdomen. Abdominal lymph node metastases with the exception of retroperitoneal and inguinal lymph nodes, signs of peritoneal spread and metastases to the lungs and liver are found in stage IVB.
Indications for MRI in endometrial cancer
In comparison to ovarian and cervical cancer, there is a debate about the usefulness of pretreatment MRI . The main reason is that endometrial cancer is treated in the majority of cases by surgery. However, therapeutic options may vary and depend on tumor stage, tumor grade and medical condition of the patient. The growing integration of radiologists in multidisciplinary teams is central in defining tailored treatment options, and imaging findings may modify the therapeutic approach . Indications for MRI with proven or suspected endometrial cancer include: high grade, serous or clear cell adenocarcinomas; suspicion of advanced disease, including cervical stroma extension and confirmation of stage III and IV disease; screening for lymph node enlargement as a roadmap for lymph node sampling; medical contraindication for surgical staging; suspected endometrial cancer with inability of curettage (e.g., cervical stenosis). The key advantage of MRI is in demonstrating stage IC disease, outer myometrial invasion or stage II disease, cervical involvement, in cases that would otherwise have been understaged or undertreated.
Preoperative lymph node imaging has been limited by the low performance of all imaging techniques, including MRI. Size criteria often do not correlate with histological findings because of the high frequency of micrometastases . This is why MRI serves rather as a roadmap for guiding lymph node sampling than for detecting stage IIIC endometrial cancer . Assessment of lymph node invasion in patients with endometrial or cervical cancer using a lymph node-specific contrast agent, ferumoxtran-10, composed of ultrasmall particles of iron oxide (USPIO), increases the sensitivity of lymph node metastasis from 29% to 93% when nanoparticle-enhanced MRI is performed . The product is evaluated in research protocols and requires injection 24 h prior to the MRI examination. Other studies in patients with prostate cancer have shown that there is no need to perform a MRI study before and after injection of nanoparticles . Further consensus is required about how to proceed for staging MRI for patients with endometrial cancer, including nanoparticle-enhanced MRI as a one-stop staging examination. According to Rockall and co-authors, the high negative predictive value of MR lymphography could potentially allow avoiding surgical lymph node dissection, whereas a positive result of MR lymphography could indicate the site of metastatic nodes to direct surgical planning or radiation therapy according to the surgical risk profile of the patient. The commercial availability of USPIO in the near future is however uncertain.
F18- FDG PET/CT is useful in detecting distant metastases and in the surveillance of recurrent endometrial cancer. Its value for staging endometrial cancer is not yet established. First data show no superiority of PET/CT compared to MRI in the detection and lymph node assessment of endometrial cancer .
There are some patients for whom lymphadenectomy will occur on the basis of factors from endometrial sampling, e.g., high-grade histology, or from basic MRI, e.g., outer myometrial or cervical invasion. Thus, newer MR technologies should be used selectively and after multidisciplinary discussion to avoid unnecessary expense.
Diffusion- weighted imaging is emerging as a promising tool in assessing gynecologic cancers. As mean ADC values of endometrial cancer are lower than that of myometrium, this technique may aid in assessing myometrial invasion . Further research is required to define if it should be included as an adjunct sequence in the preoperative assessment of endometrial cancer.
In conclusion, in patients sent for MR staging of an endometrial carcinoma, the female imaging subcommittee of the European Society of Urogenital Radiology suggested the use of at least two T2-weighted sequences followed by a single enhanced acquisition at optimal image orientation according to the results of sagittal, oblique short or long axis T2-weighted images. Selection of imaging planes requires close medical supervision during image acquisition. Further research should test the accuracy of a single high-resolution 3D gradient echo sequence in patients with endometrial cancer to diagnose myometrial and stromal invasion and evaluate the clinical utility of emerging technologies, such as nanoparticle and functional imaging. Indications for MRI include: high grade, serous or clear cell adenocarcinomas; suspicion of disease greater than stage 1B; screening for lymphadenopathy; medical contraindication for surgical staging; suspected inability of curettage.
- 12.Kinkel K (2005) Pitfalls in staging uterine neoplasm with imaging: a review. Abdom Imaging 5:5Google Scholar
- 14.Manfredi R, Gui B, Maresca G, Fanfani F, Bonomo L (2005) Endometrial cancer: magnetic resonance imaging. Abdom Imaging 6:6Google Scholar
- 15.Ohguri T, Aoki T, Watanabe H, Nakamura K, Nakata H, Matsuura Y, Kashimura M (2002) MRI findings including gadolinium-enhanced dynamic studies of malignant, mixed mesodermal tumors of the uterus: differentiation from endometrial carcinomas. Eur Radiol 12:2737–2742 Epub 2002 May 2709PubMedGoogle Scholar
- 21.Park JY, Kim EN, Kim DY, Suh DS, Kim JH, Kim YM, Kim YT, Nam JH (2008) Comparison of the validity of magnetic resonance imaging and positron emission tomography/computed tomography in the preoperative evaluation of patients with uterine corpus cancer. Gynecol Oncol 108:486–492 Epub 2008 Jan 2016PubMedCrossRefGoogle Scholar
- 22.Ortashi O, Jain S, Emannuel O, Henry R, Wood A, Evans J (2008) Evaluation of the sensitivity, specificity, positive and negative predictive values of preoperative magnetic resonance imaging for staging endometrial cancer. A prospective study of 100 cases at the Dorset Cancer Centre. Eur J Obstet Gynecol Reprod Biol 137:232–235PubMedCrossRefGoogle Scholar
- 27.Nasi F, Fiocchi F, Pecchi A, Rivasi F, Torricelli P (2005) MRI evaluation of myometrial invasion by endometrial carcinoma. Comparison between fast-spin-echo T2w and coronal-FMPSPGR Gadolinium-Dota-enhanced sequences. Radiol Med (Torino) 110:199–210Google Scholar
- 42.Rockall AG, Sohaib SA, Harisinghani MG, Babar SA, Singh N, Jeyarajah AR, Oram DH, Jacobs IJ, Shepherd JH, Reznek RH (2005) Diagnostic performance of nanoparticle-enhanced magnetic resonance imaging in the diagnosis of lymph node metastases in patients with endometrial and cervical cancer. J Clin Oncol 23:2813–2821PubMedCrossRefGoogle Scholar