• Letter to the Editor
  • Vol. 51 No. 12, 801–803
  • 27 December 2022

Diagnostic accuracy of multiparametric MRI in endometrial cancer and its adjunctive value in identifying high-risk women requiring surgical staging

Lee Lian Chew, Bernard Ji Guang Chua, Inny Busmanis, Amos Zhi En Tay, Cindy Lim, Jack Junjie Chan, Kiattissa Sommat, Sun Kuie Tay, Tew Hong Ho, Jin Wei Kwek

Dear Editor,

Endometrial cancer is the most common gynaecological cancer in developed countries, with a five-year survival rate of 81%.1,2 Prognostic factors include the International Federation of Gynecology and Obstetrics (FIGO) stage, depth of myometrial invasion (MI), lymph node involvement, cervical stromal involvement, and histological grade. Total hysterectomy with bilateral salpingo-oophorectomy (THBSO), pelvic and para-aortic lymph node dissection is the standard staging procedure for endometrial cancer.3 Decision on adjuvant therapy for endometrial carcinomas is based upon clinicopathologic factors such as FIGO stage and tumour grade.4 Multiparametric magnetic resonance imaging (mpMRI) has been reported to have high sensitivity and specificity in the detection of deep MI.5-7

We sought to evaluate the diagnostic accuracy of pelvic mpMRI in determining MI and the adjunctive value that it may add to high-grade carcinoma detected on endometrial biopsy (“high-grade endometrial biopsy”) in identifying high-risk patients (deep MI or ≥ Stage 1B disease).

We reviewed consecutive cases of all primary endometrial cancers on the database at the National Cancer Centre Singapore over a 5-year period from 1 January 2010 to 31 December 2014. The inclusion criteria were: patients with newly diagnosed non-metastatic primary endometrial carcinomas, preoperative pelvic mpMRI, THBSO performed with curative intent, pathological review, and management plan discussed at the Gynaecologic Oncology tumour board. Cases with synchronous tumours or insufficient data were excluded.

Our MRI protocol included anatomical T1-weighted and T2-weighted sequences, combined with functional diffusion-weighted imaging and dynamic contrast-enhanced (DCE) imaging. The depth of MI was measured on MRI and then dichotomised as <50% or ≥50%.

All pathological specimens were reviewed by 2 gynaecologic pathologists. The microscopic depth of MI in millimetres (mm) in relation to the total thickness of the myometrium was classified as <50% or ≥50% without reference to MRI findings.

A total of 171 cases were analysed. There were 72 (42.1%) cases classified as FIGO Stage ≥1B. The majority (152/171, 88.9%) were of the endometrioid adenocarcinoma subtype. Lymph node dissection was performed in 149/171 (87.1%) of cases, of which 17/149 (11.4%) were positive for lymph node involvement.

Of the 171 cases, 64 (37.4) were found to have radiologic evidence of deep MI while 59 (34.5%) showed histopathologic evidence of deep MI. The overall sensitivity was 81.4% (95% confidence interval [CI] 69.1–90.3) and the specificity was 85.7% (95% CI 77.8–91.6). The positive predictive value (PPV) was 75.0% (95% CI 65.2–82.8) and the negative predictive value (NPV) was 89.7% (95% CI 83.6–93.7). The positive likelihood ratio (LR+) was 5.69 (95% CI 3.56–9.11) and the negative likelihood ratio (LR-) was 0.22 (95% CI 0.13–0.37).

The overall sensitivity of preoperative pelvic mpMRI in the detection of ≥ Stage 1B disease was 66.7% (95% CI 54.6–77.3) and specificity was 83.8% (95% CI 75.1–90.5). The PPV was 75.0% (95% CI 65.1–82.9) and the NPV was 77.6% (95% CI 71.2– 82.9). The LR+ was 4.12 (95% CI 2.56–6.65) and the LR- was 0.40 (95% CI 0.28–0.56) (Table 1).

In this analysis, 130 (76%) cases with pre-hysterectomy endometrial biopsy performed were included. In the detection of deep MI (≥50%), sensitivity increased from 37.2% (high-grade endometrial biopsy alone) to 90.7% with the addition of preoperative pelvic mpMRI. PPV increased from 50.0% to 60.0% and NPV increased from 72.5% to 93.9%. LR+ increased from 2.02 to 3.03.

In the detection of ≥ Stage 1B disease, sensitivity increased from 34.6% (high-grade endometrial biopsy alone) to 76.9% with the addition of preoperative pelvic mpMRI. PPV increased from 56.3% to 61.5% and NPV increased from 65.3% to 81.5%. LR+ increased from 1.93 to 2.40.

Depth of MI is the most important prognostic factor in endometrial cancer with a strong correlation to tumour grade, cervical extension, and lymph node involvement.8-10 DCE imaging shows higher sensitivity in detecting deep MI compared to single-phase contrast-enhanced imaging.7

Our study showed that mpMRI yielded a sensitivity of 81.4% and specificity of 85.7% in the detection of deep MI (within the range reported in several meta-analyses in the literature5-7). Improved sensitivity (85.1%) and specificity (86.7%) were obtained when cases of non-endometrioid histology subtypes were excluded.

In the identification of patients with ≥ Stage 1B disease, preoperative pelvic mpMRI has moderate sensitivity of 66.7% but maintains a high specificity of 83.8%. The low false positive rate improves the selection of patients who are likely to have higher risk features other than MI alone, such as cervical involvement, parametrial extension and lymph node involvement, thereby reducing the likelihood of low-risk patients having to undergo more extensive surgery unnecessarily.

The tumour grade of endometrial biopsy is a significant prognostic factor in endometrial cancer and a grade 3 lesion is associated with deep MI. Our results showed high specificity (81.6%) for preoperative high-grade endometrial biopsy in predicting MI ≥50%. However, its sensitivity is unacceptably low (37.2%), indicating a significant proportion of patients with grade 1 or 2 preoperative endometrial biopsy also have deep MI. The addition of pelvic mpMRI to endometrial biopsy grading improved sensitivity while maintaining moderate specificity. This highlights the adjunctive value of mpMRI to preoperative endometrial biopsy as it considers not only inherent disease biology based on grading but also the extent of tumour progression in terms of MI at the time of diagnosis when treatment decisions need to be made.

In the detection of deep MI or high-risk (≥ Stage 1B) disease, mpMRI alone provided moderate to high sensitivity and specificity. When utilised together with preoperative endometrial biopsy grading, there was a further increase in sensitivity with a slight reduction in specificity. This is important as it helps to exclude lower-risk patients from having to undergo full surgical staging, including pelvic lymphadenectomy.

We reviewed discordant cases to understand the intrinsic limitations in the accuracy of mpMRI in predicting the depth of MI. The presence of fibroids was the most common contributing factor. Other factors include difficulty in obtaining an accurate measurement in cases where the native myometrium was very thin, the presence of myometrial adenomyosis, and the nature of the tumour invasion pattern.

Based on our findings, preoperative mpMRI provides moderate sensitivity and specificity in detecting deep MI in endometrial cancer and provides an adjunctive value in improving the sensitivity of detecting high-risk women requiring full surgical staging compared to endometrial biopsy alone.

Acknowledgements

The authors would like to thank Drs Minnie Pang, Chew Ghee Kheng, Khoo Tan Hoon Seng, Ravichandran Nadarajah, Chay Wen Yee, Elaine Lim Hsuen and Soh Lay-Tin, as well as Senior Staff Nurse Grace Su for their contributions to the Gynaecologic Oncology tumour board at the National Cancer Centre Singapore.

REFERENCES

  1. National Cancer Institute, Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Uterine Cancer. https://seer. cancer.gov/statfacts/html/corp.html. Accessed 26 April 2020.
  2. National Cancer Centre Singapore. Cancer Statistics. https://www.nccs.com.sg/patient-care/cancer-types/cancer-statistics, 2021. Accessed 26 April 2020.
  3. Gasparri ML, Caserta D, Benedetti Panici P, et al. Surgical staging in endometrial cancer. J Cancer Res Clin Oncol 2019;145:213-21.
  4. National Comprehensive Cancer Network. NCCN Guidelines Version 1.2020 Uterine Neoplasms. https://www.nccn.org/professionals/ physician_gls/pdf/uterine.pdf. Accessed 5 May 2020.
  5. Das SK, Niu XK, Wang JL, et al. Usefulness of DWI in preoperative assessment of deep myometrial invasion in patients with endometrial carcinoma: a systematic review and meta-analysis. Cancer Imaging 2014;14:32.
  6. Andreano A, Rechichi G, Rebora P, et al. MR diffusion imaging for preoperative staging of myometrial invasion in patients with endometrial cancer: a systematic review and meta-analysis. Eur Radiol 2014;24:1327-38.
  7. Luomaranta A, Leminen A, Loukovaara M. Magnetic resonance imaging in the assessment of high-risk features of endometrial carcinoma: a meta-analysis. Int J Gynecol Cancer 2015;25:837-42.
  8. Singh N, Hirschowitz L, Zaino R, et al. Pathologic Prognostic Factors in Endometrial Carcinoma (Other Than Tumor Type and Grade). Int J Gynecol Pathol 2019;38 Suppl 1:S93-113.
  9. Sala E, Crawford R, Senior E, 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;19:141-6.
  10. Euscher E, Fox P, Bassett R, et al. The pattern of myometrial invasion as a predictor of lymph node metastasis or extrauterine disease in low-grade endometrial carcinoma. Am J Surg Pathol 2013;37:1728-36.

RELATED ARTICLES

More related articles