What is the role of preoperative imaging for low and high risk apparent early stage endometrial cancer?
What is the role of preoperative imaging for low and high-risk apparent early stage endometrial cancer?
The use of some imaging techniques prior to definitive surgical treatment is routine in many gynaecological cancer treatment centres, but the evidence for this practice is unclear. If pretreatment imaging is to be of any value then it should influence patient management, such that the findings are used to determine the appropriateness, type and extent of planned surgery or treatment.
In Australia the possible indications for imaging in this situation are three-fold:
- To exclude metastatic disease in the pelvis (adnexae or pelvic lymph nodes) or distant sites (lung, liver, omentum, peritoneal cavity or aortic nodes) in whom surgical treatment is planned.
- To ‘stage’ tumours in women who are unsuited to full surgical staging by reason of morbid obesity and/or other medical co-morbidities.
- To triage women who will most likely benefit from full surgical staging/lymphadenectomy by predicting the presence of locally advanced disease (deep myometrial invasion and/or cervical stromal involvement) as a surrogate for increased likelihood of pelvic/aortic node metastasis.
In Australia, recommended best practice for women with endometrial cancer is that they be managed by a gynaecological oncologist who will incorporate full surgical staging into the planned treatment where appropriate, thus minimising the value of predictive pre-operative imaging. Preoperative imaging may be appropriate for women who live in rural areas remote from subspecialist treatment centres who could potentially be treated by a local community gynaecologist without the need for full surgical staging.
The majority of women diagnosed with endometrioid adenocarcinoma of endometrium (EAC) will have a small uterus with grade 1-2 histology and will be at low risk of metastatic disease in the pelvis and elsewhere. The yield from a ‘metastatic imaging work up’ will be low in terms of discovering ‘radiologically apparent’ and clinically unsuspected spread of the disease.
The following imaging techniques can be considered:
- Transvaginal Ultrasound (TVS)
- Computed Tomography (CT)
- Magnetic Resonance Imaging (MRI)
- Positron Emission Tomography (PET)
- Chest X Ray
Transvaginal Ultrasound (TVS)
Many women who have been diagnosed with endometrial cancer will have already had a transvaginal ultrasound as part of their diagnostic investigations, providing valuable information regarding the size of the uterus and the presence or absence of adnexal masses.
TVS is reasonably accurate (70-90% PPV) in the prediction of deep myometrial invasion and is inexpensive in comparison to CT and MRI. Van Doorn considered TVS to be only moderately reliable in the prediction of deep myometrial invasion, but when combined with patient age and degree of tumour differentiation in the curettings it was possible to preoperatively select women at high risk of lymph node metastases with sufficient reliability. Use in the Australian setting is unlikely to alter management decisions.
Computed tomography (CT)
Several retrospective studies have suggested that pelvic and abdominal CT scanning has limited utility in the preoperative assessment of women with endometrial carcinoma. CT showed poor prediction of nodal disease and depth of myometrial invasion though it was suggested it could have some utility in high-risk histologic types such as clear cell and serous papillary.
In the largest and most recent series, Bansal reviewed the records of 762 women with uterine malignancies between 1990-2006. Abdomino-pelvic CT scans were performed preoperatively in 250 women (32 sarcoma and 218 with carcinoma) and CT findings were correlated with intraoperative and histopathologic data. The analysis focused on extranodal metastatic disease and any other incidental findings, and their capacity to alter the planned management. Extra nodal disease was found in 22 (9%) of women (adnexa 10, omentum 4, bowel 3, ascites 1) but patient management was altered in only seven (3%). Of these seven women, four had grade 3 EAC, one had a sarcoma and the other two had grade 1 EAC. Incidental findings were noted in 43 (17%) and management altered in only seven (3%) of these women in whom the findings were considered important, namely renal mass in five, severe diverticular disease requiring resection in one and a retroperitoneal mass with hydronephrosis due to squamous carcinoma in one patient. Further analysis based on preoperative histologic diagnosis showed that CT findings were more likely to alter management (10.7%) in women with high-risk serous papillary and clear cell histologic subtypes.
They concluded that routine CT scanning of women with EAC is costly, of limited value and rarely alters treatment, but may have some utility in women with high-risk histology.
(It should be noted that in the USA, where this study was done, it is recommended that full surgical staging be carried out on all women and, therefore, the predictive role of imaging is of less importance.)
However, in some situations the addition of a CT scan of thorax, abdomen and pelvis may be useful in defining or excluding distant metastases or local extension of the disease to the adnexae or pelvic/aortic lymph nodes. Such circumstances include:
- Symptoms (cough, bloating, pain)
- Physical signs (ascites, enlarged liver, upper abdominal mass, adnexal mass, cervical lesion)
- Abnormal biochemical or haematological investigations (liver function tests, CA125 etc)
- High-risk histologies (clear cell, serous papillary) or high-grade (3) endometrioid carcinoma
In Australia and elsewhere there is a trend toward a laparoscopic surgical approach to endometrial cancer, thus reducing the opportunity for full visual exploration and palpation of the peritoneal cavity and aortic and pelvic retroperitoneal nodes (see section on Hysterectomy). In patients in whom a laparoscopic approach is planned, it may be useful to perform a CT scan of abdomen and pelvis to exclude gross pelvic organ abnormality, or retroperitoneal nodal enlargement.
Magnetic Resonance Imaging (MRI)
MRI has been shown to be an accurate tool for the measurement of the depth of myometrial invasion by endometrial carcinoma though an isointense junctional zone, polypoid tumours or presence of leiomyomas may lead to an underestimate of myometrial invasion. This study showed 83.3% accuracy in differentiating deep from superficial invasion in 100 of 120 cases.
In a comprehensive literature review of the conservative management of endometrial cancer in young women, Erkanli suggested that MRI may be of assistance specifically in assessing the absence of invasion. In a recent Australian study, Cade reported on progestogen treatment options for early endometrial cancer and considered an MRI scan negative for myometrial invasion or extension to the cervix an essential prerequisite to conservative treatment.
In contrast, Nakao has reported that although MRI is good at determining deep myometrial invasion it is not as accurate in assessing the absence of microscopic myometrial invasion. This view is supported by an Australian study in which Cade questions whether radiological staging is sufficient for planning conservative treatment. This study compared MRI scans and final histopathological diagnoses of 111 patients with endometrioid adenocarcinoma over a six year period at a tertiary centre. They reported that MRI had a high negative predictive value (NPV) for the presence of deep invasion (87% overall and 95% for grade 1 disease), but a poor NPV for the presence of any myometrial invasion, making it less reliable in predicting the absence of invasion. However, if the new revised 2008 FIGO staging system was used then stage 1A ( no invasion or up to 50% invasion) was more accurately predicted using MRI, making it very useful if clinicians were to consider all patients with stage 1A disease to be eligible for conservative treatment when fertility was desired. This is not current standard practice and more research is needed in this area.
In a retrospective review of 182 women diagnosed with clinical stage 1 disease, Cho et al studied the accuracy of preoperative investigations. They found that MRI correctly differentiated stage 1a, Ib and 1c disease in 58.2% (150/182) of patients but that the sensitivity and specificity of MRI in detecting lymph node metastases was only 45% and 80.8% respectively. They concluded that the inaccuracy of MRI would lead to incorrect surgical treatment in a substantial number of patients and that full systematic lymphadenectomy was necessary to determine the stage of the disease and tailor subsequent adjuvant therapy.
MRI has been shown to be accurate in the prediction of cervical stromal involvement with a positive predictive value of 89.8% in a study of 135 consecutive women. This is important as it will allow for an informed decision regarding the type of hysterectomy to be performed: radical rather than simple.
Celik evaluated cervical involvement in endometrial cancer by comparing transvaginal sonography (TVS), MRI and intraoperative frozen section in 64 consecutive patients. The accuracy rates of TVUS, MRI and frozen section were 90.6%, 92.2% and 95.5% respectively. Obviously frozen section does not allow for alteration of the type of hysterectomy to be offered but will suggest the need for lymphadenectomy in patients without other high-risk prognostic factors. MRI was noted to be more time consuming and expensive than TVUS but could be recommended in cases where the TVUS was of poor quality. MRI was found to be more reliable than diagnostic fluid mini-hysteroscopy and TVS in predicting cervical involvement with a positive predictive value of 71%, a negative predictive value of 94% and an accuracy rate of 91%.
A meta-analysis of radiologic staging in patients with endometrial cancer was reported by Kinkel. There were insufficient studies of CT and TVS for meaningful meta-analysis in regard to cervical involvement, but MRI showed equal specificity and sensitivity of 92% for prediction of cervical involvement.
Most authors have suggested that gadolinium contrast enhanced MRI is better for prediction of deep myometrial invasion, but others have found no difference between T2 weighted and contrast enhanced MRI.
MRI may be used to assess the depth of myometrial invasion in order to predict women with deep invasion greater than 50% of myometrial thickness and this finding has utility as a surrogate for the likelihood of lymph node metastases and to determine appropriate surgical treatment.
It should be noted that nearly all of the MRI literature relates to the old FIGO 1988 staging. There is only one report regarding the efficiency of MRI in FIGO 2009 staged cases compared with FIGO 1988 staging. Ballester reported that MRI staging was more accurate using FIGO 2009 but only moderately better. It is possible that as more work is reported using FIGO 2009, the role of routine MRI will be clearer but at present the evidence is lacking.
MRI may be used in subspecialist tertiary centres for the assessment of cervical stromal involvement and appropriate surgical planning.
Positron Emission Tomography (PET)
The use of positron emission tomography using fluoro-2-deoxyglucose (FDG-PET) has been studied in the preoperative evaluation of endometrial cancer. FDG-PET has a sensitivity of 83.3% in detecting extrauterine lesions (excluding retroperitoneal nodes) and was useful in providing additional information regarding lesions detected on CT/MRI that were of uncertain significance. FDG-PET was not able to identify any lymph node metastasis less than 1cm in diameter, and therefore a negative finding is not a reason to omit retroperitoneal lymph node dissection.
Park retrospectively compared the validity of MRI and PET/CT in the preoperative evaluation of 53 women with endometrial cancer. There was no difference in the ability of MRI or CT/PET to detect lymph node metastases and it was concluded that PET/CT could not replace surgical staging, but because of its high negative predictive value in predicting lymph node and distant metastases, it could be helpful in the assessment of patients who are unsuited for full surgical staging.
Signorelli prospectively studied FDG-PET/CT in 37 fully surgically staged women confirming the results of other authors and the limitation in detecting nodal lesions of 5mm or less, probably related to the limited spatial resolution of PET/CT scanners used in the study. They noted an accuracy of 94.4% in detecting nodal disease and concluded that the high NPV of 93.1% may be useful in selecting patients who may benefit from lymphadenectomy.
PET or PET/CT may be used in subspecialist tertiary centres for the assessment of some patients and appropriate surgical planning. It is more commonly used post operatively, when the surgico-pathological findings show locally advanced disease or pelvic node involvement, in order to direct appropriate adjuvant therapy.
Chest X Ray
Chest X Ray is part of the routine preoperative assessment of patients being considered for major surgery and may detect unexpected metastatic disease. While the yield is relatively low, it is cost effective, has low dose exposure and should remain a part of routine pre-operative assessment.
Is there a role for preoperative imaging in endometrial carcinoma?
In Australia it is recommended that women with endometrial carcinoma are treated by gynaecological oncologists within specialist gynaecological oncology units. Patients have selective surgical staging based on tumour grade and histologic type and intraoperative assessment. Gynaecological oncologists have the facility to perform intraoperative uterine assessment and full surgical staging where indicated and consequently there is a reduced role for routine ‘predictive’ preoperative imaging.
If patients have symptoms, physical signs or abnormal blood tests suggestive of metastatic disease, then appropriate imaging, usually an abdomino-pelvic CT, is indicated to exclude pelvic or distant metastases. If there is a suspicion of cervical involvement then an MRI may be informative and guide surgical treatment.
For rural patients who are reluctant to travel to a gynaecological cancer centre for their treatment, and for whom the use of MRI to predict deep myometrial or cervical stromal involvement is not an option, Transvaginal scanning by an experienced practitioner or abdomino-pelvic CT may also be of assistance, as these investigations are more likely to be available in a community setting.
In women who are unsuited to full surgical staging by reason of morbid obesity or other medical co-morbidities, then MRI or FDG-PET/CT may be indicated to assist in ‘staging’ the patient. This will allow more accurate targeting of adjuvant or nonsurgical management
A Canadian population based study reviewed records of 12,522 women treated for uterine adenocarcinoma or sarcoma between 1995 and 2005. A preoperative TVS was performed in 9145 (73%) women and 1148 (9.2%) had a CT and/or MRI. Over the ten year period the use of CT had increased 4.5 fold and MRI use increased 10.6 fold. Significantly higher rates of CT/MRI use were seen in non-endometrioid high risk histology (33.5% versus 14.6%). Half of these tests were ordered by non-gynaecologists and the time from diagnosis to surgery was two weeks longer for women who had a CT/MRI. Given the questionable utility of preoperative CT/MRI in this disease, they recommended that guidelines be developed for the use of such imaging tests in uterine cancer.
While the evidence for many of the imaging tests done pre-operatively is inconsistent and must be interpreted in the setting in which a patient is being managed, tests that will alter or help patient management should be considered.
Evidence summary and recommendations
|Abdomino-pelvic CT scan has limited utility in the preoperative assessment of women with endometrial carcinoma with poor prediction of nodal disease and depth of myometrial invasion.||III-2||, , , |
|Abdomino-pelvic CT scan may have some utility in discovering or excluding distant metastases or locally advanced pelvic disease particularly in high-risk histologic types or high-grade endometrioid adenocarcinoma of the endometrium.||III-2||, |
|Preoperative abdomino-pelvic CT scan is indicated in patients who have symptoms, signs or blood tests suggestive of metastatic disease or high-grade or high-risk histologic type of endometrial carcinoma.||C|
|MRI is an accurate test for preoperative prediction of cervical involvement by endometrial carcinoma.||I, II||, , |
|Preoperative MRI may be helpful when there is clinical suspicion of cervical involvement as confirmation will guide surgical management.||B|
|MRI is the most accurate method of preoperative prediction of depth of myometrial invasion by endometrial carcinoma.||I, II, III-1||, , , |
|Preoperative tests based on tumour grade and MRI prediction of myometrial invasion are inaccurate in risk stratification for nodal metastases and fail to detect a small proportion of high-risk patients.||III-2|||
|PET scan has a high negative predictive value for lymph node and distant metastases in endometrial carcinoma.||II, III-2||, , |
|Preoperative ‘predictive’ imaging may be useful in patients who are not suited to full surgical staging and may assist in ‘staging’ and planning management.||C|
|MRI is good at preoperative prediction of deep myometrial invasion but is less accurate at completely excluding superficial microscopic myometrial invasion.||III-2|||
|MRI is the best available method of determining the likely absence of myometrial invasion in women desiring conservative management of endometrial carcinoma and wishing to retain fertility.||IV|||
|Preoperative MRI may assist in the assessment of patients wishing to retain fertility.||D|
- ↑ Ruangvutilert P, Sutantawibul A, Sunsaneevithayakul P, Boriboonhirunsarn D, Chuenchom T. Accuracy of transvaginal ultrasound for the evaluation of myometrial invasion in endometrial carcinoma. J Med Assoc Thai 2004 Jan;87(1):47-52 Available from: http://www.ncbi.nlm.nih.gov/pubmed/14971534.
- ↑ Takac I. Transvaginal ultrasonography with and without saline infusion in assessment of myometrial invasion of endometrial cancer. J Ultrasound Med 2007 Jul;26(7):949-55; quiz 956-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17592058.
- ↑ 3.0 3.1 3.2 Celik C, Ozdemir S, Kiresi D, Emlik D, Tazegül A, Esen H. Evaluation of cervical involvement in endometrial cancer by transvaginal sonography, magnetic resonance imaging and frozen section. J Obstet Gynaecol 2010 Apr;30(3):302-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20373937.
- ↑ van Doorn HC, van der Zee AG, Peeters PH, Kroeks MV, van Eijkeren MA. Preoperative selection of patients with low-stage endometrial cancer at high risk of pelvic lymph node metastases. Int J Gynecol Cancer 2002;12(2):144-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11975673.
- ↑ 5.0 5.1 5.2 Connor JP, Andrews JI, Anderson B, Buller RE. Computed tomography in endometrial carcinoma. Obstet Gynecol 2000 May;95(5):692-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10775731.
- ↑ 6.0 6.1 6.2 Zerbe MJ, Bristow R, Grumbine FC, Montz FJ. Inability of preoperative computed tomography scans to accurately predict the extent of myometrial invasion and extracorporal spread in endometrial cancer. Gynecol Oncol 2000 Jul;78(1):67-70 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10873413.
- ↑ 7.0 7.1 7.2 7.3 7.4 Bansal N, Herzog TJ, Brunner-Brown A, Wethington SL, Cohen CJ, Burke WM, et al. The utility and cost effectiveness of preoperative computed tomography for patients with uterine malignancies. Gynecol Oncol 2008 Nov;111(2):208-12 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18789515.
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 Gien LT, Barbera L, Kupets R, Saskin R, Paszat L. Utilization of preoperative imaging in uterine cancer patients. Gynecol Oncol 2009 Nov;115(2):226-30 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19683807.
- ↑ 9.0 9.1 9.2 Chung HH, Kang SB, Cho JY, Kim JW, Park NH, Song YS, et al. Accuracy of MR imaging for the prediction of myometrial invasion of endometrial carcinoma. Gynecol Oncol 2007 Mar;104(3):654-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17095081.
- ↑ 10.0 10.1 Erkanli S, Ayhan A. Fertility-sparing therapy in young women with endometrial cancer: 2010 update. Int J Gynecol Cancer 2010 Oct;20(7):1170-87 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21495221.
- ↑ Cade TJ, Quinn MA, Rome RM, Neesham D. Progestogen treatment options for early endometrial cancer. BJOG 2010 Jun;117(7):879-84 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20394609.
- ↑ 12.0 12.1 Nakao Y, Yokoyama M, Hara K, Koyamatsu Y, Yasunaga M, Araki Y, et al. MR imaging in endometrial carcinoma as a diagnostic tool for the absence of myometrial invasion. Gynecol Oncol 2006 Aug;102(2):343-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16469365.
- ↑ Cade TJ, Quinn MA, McNally OM, Neesham D, Pyman J, Dobrotwir A. Predictive value of magnetic resonance imaging in assessing myometrial invasion in endometrial cancer: is radiological staging sufficient for planning conservative treatment? Int J Gynecol Cancer 2010 Oct;20(7):1166-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21495220.
- ↑ 14.0 14.1 Cho H, Kim YT, Kim JH. Accuracy of preoperative tests in clinical stage I endometrial cancer: the importance of lymphadenectomy. Acta Obstet Gynecol Scand 2010;89(2):175-81 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19943822.
- ↑ 15.0 15.1 Nagar H, Dobbs S, McClelland HR, Price J, McCluggage WG, Grey A. The diagnostic accuracy of magnetic resonance imaging in detecting cervical involvement in endometrial cancer. Gynecol Oncol 2006 Nov;103(2):431-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16697034.
- ↑ 16.0 16.1 Cicinelli E, Marinaccio M, Barba B, Tinelli R, Colafiglio G, Pedote P, et al. Reliability of diagnostic fluid hysteroscopy in the assessment of cervical invasion by endometrial carcinoma: a comparative study with transvaginal sonography and MRI. Gynecol Oncol 2008 Oct;111(1):55-61 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18701154.
- ↑ 17.0 17.1 17.2 17.3 Kinkel K, Kaji Y, Yu KK, Segal MR, Lu Y, Powell CB, et al. Radiologic staging in patients with endometrial cancer: a meta-analysis. Radiology 1999 Sep;212(3):711-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10478237.
- ↑ 18.0 18.1 18.2 Frei KA, Kinkel K, Bonél HM, Lu Y, Zaloudek C, Hricak H. Prediction of deep myometrial invasion in patients with endometrial cancer: clinical utility of contrast-enhanced MR imaging-a meta-analysis and Bayesian analysis. Radiology 2000 Aug;216(2):444-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10924568.
- ↑ 19.0 19.1 19.2 Sala E, Crawford R, Senior E, Shaw A, Simcock B, Vrotsou K, et al. Added value of dynamic contrast-enhanced magnetic resonance imaging in predicting advanced stage disease in patients with endometrial carcinoma. Int J Gynecol Cancer 2009 Jan;19(1):141-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19258956.
- ↑ 20.0 20.1 20.2 Rockall AG, Meroni R, Sohaib SA, Reynolds K, Alexander-Sefre F, Shepherd JH, et al. Evaluation of endometrial carcinoma on magnetic resonance imaging. Int J Gynecol Cancer 2007;17(1):188-96 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17291252.
- ↑ Takahashi S, Murakami T, Narumi Y, Kurachi H, Tsuda K, Kim T, et al. Preoperative staging of endometrial carcinoma: diagnostic effect of T2-weighted fast spin-echo MR imaging. Radiology 1998 Feb;206(2):539-47 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9457210.
- ↑ 22.0 22.1 Ballester M, Koskas M, Coutant C, Chéreau E, Seror J, Rouzier R, et al. Does the use of the 2009 FIGO classification of endometrial cancer impact on indications of the sentinel node biopsy? BMC Cancer 2010 Aug 30;10:465 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20804553.
- ↑ 23.0 23.1 23.2 23.3 Suzuki R, Miyagi E, Takahashi N, Sukegawa A, Suzuki A, Koike I, et al. Validity of positron emission tomography using fluoro-2-deoxyglucose for the preoperative evaluation of endometrial cancer. Int J Gynecol Cancer 2007;17(4):890-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17343574.
- ↑ 24.0 24.1 24.2 24.3 Park JY, Kim EN, Kim DY, Suh DS, Kim JH, Kim YM, et al. 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 2008 Mar;108(3):486-92 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18201753.
- ↑ 25.0 25.1 25.2 25.3 Signorelli M, Guerra L, Buda A, Picchio M, Mangili G, Dell'Anna T, et al. Role of the integrated FDG PET/CT in the surgical management of patients with high risk clinical early stage endometrial cancer: detection of pelvic nodal metastases. Gynecol Oncol 2009 Nov;115(2):231-5 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19695685.