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Additional diagnostic value of Diffusion-Weighted Magnetic Resonance Imaging to conventional Magnetic Resonance Imaging in local staging of primary uterine cervical cancer

Objective: Magnetic resonance (MR) imaging is a helpful modality for detecting and staging gynecological cancers. Diffusion-weighted imaging (DWI) could improve the accuracy rates of MR imaging. The aim of this study was to assess the additional diagnostic value of DWI over conventional MR imaging in assessing the local extent of primary cervical cancer. Method: Forty patients with primary uterine cervical cancer were enrolled in the study, prospectively. All MR examinations were performed using a 1.5 Tesla Unit MR with a body coil. Sagittal and axial T2-weighted MR images, sagittal and axial DWI (at b values of 0, 500,1000 s/mm 2 ) with ADC maps were obtained. The images were evaluated by two different readers independently. The degree of the interobserver agreement between the radiologists was assessed with kappa statistics. Results: Mean age of the study population was 50.7±11.1 years. Kappa values ranged from 0.76 to 1 for both readers, indicating excellent agreement. Accuracy rates were as follows for reader 1 respectively with conventional and conventional plus DWI; stromal invasion 0.92/0.95; parametrial invasion 0.87/0.92; vaginal invasion 0.87/0.92; pelvic sidewall invasion 0.90/0.97. Accuracy rates were as follows for reader 2 respectively with conventional and conventional plus DWI images; stromal invasion 0.90/0.95; parametrial invasion 0.87/0.92; vaginal invasion 0.87/0.97; pelvic sidewall invasion 0.90/0.95. Conclusions: MR provides satisfactory accuracy rates in the evaluation of the local extent of uterine cervical carcinoma, and adding DWI improves the diagnostic performance of conventional MR.


INTRODUCTION
Uterine cervical cancer is the third most common gynecological malignancy in the world 1 . Although surgery still remains as the most accurate diagnostic approach in staging the disease, pre-surgical imaging of the tumor provides very helpful information, particularly about the local extent of the disease 2 .
The most crucial prognostic factor in cervical cancer staging is the infiltration of the parametrium. Parametrial invasion is also a cutoff criterion for extended surgical approach 3,4 . Patients with parametrial invasion are often treated with primary chemoradiotherapy or may need adjuvant treatment after surgery. Routine parametrectomy is not preferred in the treatment of early-stage cervical cancer because of its association with increased morbidity and mortality 5,6 . Moreover, the presence of parametrial invasion in uterine cervical cancer associated with disease recurrence and decreased survival rates 7,8 . Therefore, accurate prediction of the parametrial status is essential for appropriate treatment planning and improves patient outcomes.
Magnetic resonance (MR) imaging is an appropriate imaging modality for presurgical staging of cervical cancer with high image resolution 9,10 . Diffusion-weighted magnetic resonance imaging (DWI) is used to evaluate malignant lesions. It provides helpful information about water mobility and tumor cellularity. In the literature, several studies that analyze the additional value of DWI in assessing oncologic staging and therapy response of abdominal tumors have been published.
Herein, we aimed to assess the additional diagnostic value of DWI over T2-weighted MR for detection and assessing deep stromal and parametrial invasion of primary cervical carcinoma.

MATERIAL AND METHODS
This prospective study was approved by the Institutional Review Board and Ethics Committee and supported by the Baskent University Research Fund (project number: KA11/98). Written informed consent was obtained from each subject before the MR examination. 40 patients who had primary cervical cancer without any treatment prospectively underwent MR examination. Exclusion criteria included contraindications to MR imaging (e.g., cardiac pacemakers), receiving any radiation therapy or chemotherapy. Cervical carcinoma was confirmed in all 40 patients, either by surgery (29 patients) or by biopsy (11 patients). 29 patients underwent hysterectomy with or without lymph node dissection. 10 of the patients had advanced cervical carcinoma, and they were directed to radiation therapy with or without chemotherapy. One patient had a low-grade cervical carcinoma, but she couldn't have surgery because of high risk due to cardiac problems.
All patients were staged clinically according to the FIGO staging system at the time of the diagnosis. Other diagnostic tests, including cystoscopy or rectosigmoidoscopy, were performed if needed due to the evaluation of the gynecologic oncologist. FIGO staging was determined after a detailed examination of each patient.
DWI was performed by sagittal and axial orthogonal planes to the cervix by using singleshot diffusion-weighted echo-planar (102x160 matrix; 27 cm a field of view; 102 EPI factor, 96, reconstructed to 128; a field of view, 20 cm; and section thickness, 4 mm) sequences. b Values of 0, 500, and 1000 sec/mm 2 were used.
All MR images were interpreted independently by two radiologists. All MR images were evaluated with respect to the status of the stroma, parametrium, vagina, and pelvic sidewall.
Each reader assigned an overall suspicion score for the probability of the invasion of each parameter on a five-point index scale (1 = invasion is definitely absent, 2 = probably absent, 3 = indeterminate, 4 = probably present, 5 = definitely present). In the first session, readers evaluated only sagittal and axial T2 weighted images. One month after the first session, they evaluated each patient with DWI, blinded to their first reading.

Statistical Analysis
All statistical analysis was performed using statistical software (SPSS, version 15.O; Chicago, IL, USA). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rates were calculated. The degree of the interobserver agreement between the two radiologists was assessed with kappa statistics. The reference Kappa values were interpreted as follows: Kappa value less than 0.40, poor agreement; 0.41-0.75, moderate to the good agreement; and greater than 0.75, excellent agreement. Values of p < 0.05 were considered statistically significant.

RESULTS
The mean age of the study population was 50.7±11.1 years.
The histologic subtypes of the patients were; squamous cell carcinoma (n=36) and adenocarcinoma (n=4).
The deep stromal invasion was identified in 33 of the 40 patients (%82.5) and negative in 7 patients (17.5%) (Figure1). Adding DWI increased accuracy rates from 0.92 to 0.95 for reader 1, and from 0.90 to 0.95 for reader 2. Diagnostic performances of both readers in assessing deep stromal invasion were summarized in Table 1.  Diagnostic performances of both readers in assessing parametrial invasion were summarized in Table 2.   Table 3. Diagnostic performances of both readers in the pelvic sidewall invasion were summarized in Table 4.

DISCUSSION
In the present study, we searched the additional diagnostic value of DWI in assessing the local extent of uterine cervical cancer. Adding DWI improved accuracy rates for both readers in assessing the extent of disease to the stroma, parametrium, vagina, and pelvic sidewall.
The parametrial status is one of the most important factors in planning the treatment of uterine cervical cancer.
Previously in the literature, MR showed high accuracy rates from %80 to 94% for assessing parametrial invasion with conventional MR sequences [11][12][13] . Only T2weighted imaging has been reported to reach approximately 75% sensitivity and 70% specificity in the accurate evaluation of parametrial status 14 . Our results correlate well with these results. Moreover, T2-weighted imaging has been suggested as the clinical standard for preoperative assessment of cervical carcinoma because of its high soft tissue resolution in showing the zonal anatomy of the uterus 15 18 . We showed sensitivity rates from 0.93 to 0.96 and specificity rates from 0.71 to 0.85 in our study. MR showed high sensitivity and specificity rates for assessing deep stromal invasion.
The presence of vaginal invasion is determined when the low signal intensity of the vaginal wall was disrupted by a high-intensity tumor. In the literature, previously reported studies showed accuracy rates with a range of 81%-100% for vaginal evaluation with contrast-enhanced studies 13,23 . There are limited numbers of studies in the literature with DWI. In our study, DWI improved the accuracy rates for both readers in assessing vaginal invasion.
Accurate staging of the pelvic sidewall is also important, and MR provides excellent images of the pelvic floor anatomy. Pelvic sidewall involvement (stage IIIB) is diagnosed when a tumor is seen within 3 mm from the internal obturator, levator ani or pyriformis muscles; encasement of the iliac vessels is also diagnostic for pelvic sidewall invasion 24 . The presence of hydronephrosis/hydroureter should also be investigated. Our study showed promising and reliable results in assessing the status of the pelvic sidewall with DWI.