Abstract
Background/Aim: Diagnosis of cervical cancer with tumor diameter <2 cm using magnetic resonance imaging alone has not been investigated. Moreover, whether tumor volume can be used for diagnosing the true tumor diameter remains unknown. Here, we investigated the utility of early cervical cancer volume index in diagnosing cervical cancer with a tumor diameter of <2 cm, which can be treated using more conservative surgery. Patients and Methods: This single-center retrospective study analyzed women who underwent radical hysterectomy for cervical cancer with a tumor diameter of <2 cm and clinical stages IA2, IB1, IB2, IB3, and IIA1 at our institute between January 2009 and April 2022. The volume index, defined as the product of the maximum longitudinal diameter along the uterine axis, maximum anteroposterior diameter (thickness) on a sagittal section image, and maximum horizontal diameter on a horizontal section image, was evaluated using either T2-weighted magnetic resonance imaging or gadolinium-enhanced T1-weighted imaging. The receiver operating characteristic curve for the volume index was also calculated. Results: The sensitivity and specificity of magnetic resonance imaging for measuring the tumor diameter were 0.92 and 0.84, respectively. The calculated cut-off value was 2.60, whereas the volume index area under the curve was 0.955, with a sensitivity of 0.92 and specificity of 0.93. Conclusion: Considering the specificity and low incidence of false-negative results, the volume index can be used for preoperative diagnosis of pT1B1 cervical cancer, which can be treated with more conservative surgery.
While open abdominal surgery is the standard treatment for early cervical cancer, several trials have investigated the potential of minimally invasive surgery for cervical cancer (1, 2), and have found that surgeons prefer to operate on tumors measuring <2 cm in size. According to the International Federation of Gynecology and Obstetrics (FIGO) 2018 guidelines, the prognosis of cervical cancer with a tumor size of >2 cm is poor. Apart from minimally invasive surgery, the ConCerv trial, a prospective trial on conservative surgery, i.e., conization, simple hysterectomy for early cervical cancer, showed that tumors measuring <2 cm can be safely managed with conization or simple hysterectomy.
The sensitivity of magnetic resonance imaging (MRI) in diagnosing cervical cancer is high; however, studies have only been conducted on parametrial invasion and lymph node involvement (3, 4), not on tumor diameter. Although previous studies recommended combining pathological findings with those of MRI for diagnosis (5), whether MRI alone can diagnose cervical cancer with a tumor diameter of <2 cm remains unknown.
In uterine corpus cancer, the tumor volume index, calculated as the product of the long, short, and horizontal tumor diameters, predicts tumor prognosis and lymph node metastasis (6-10). We hypothesized that tumor volume in cervical cancer would be as helpful in diagnosing true tumor diameter as it is for uterine body cancer. Therefore, this study investigated whether the volume index in early cervical cancer is useful for diagnosing cervical cancer with a tumor diameter of <2 cm.
Patients and Methods
In this single-centre, retrospective study, we analyzed women who underwent radical hysterectomy for cervical cancer with a tumor diameter of <2 cm and at FIGO clinical stages IA2, IB1, IB2, IB3, and IIA1 (as per the FIGO staging system) at our institution between January 2009 and April 2022 (11, 12). All pathological examinations were performed according to the American Joint Committee on Cancer staging manual (13).
This study was conducted in accordance with the principles embodied in the Declaration of Helsinki. Ethical approval was obtained from the institutional review board of Jichi Medical University, Saitama Medical Center (approval number: S19-127). The requirement for informed consent was waived due to the retrospective nature of the study.
All patients underwent preoperative MRI. The primary outcomes were sensitivity and specificity. Demographic characteristics, including age, final stage, volume index, and the final histological type, were also reviewed using medical records. The volume index was evaluated using either T2-weighted MRI or gadolinium-enhanced T1-weighted imaging. It was defined as the product of the maximum longitudinal diameter along the uterine axis, maximum anteroposterior diameter (thickness) on a sagittal section image, and maximum horizontal diameter on a horizontal section image. The patients were divided into two groups: those with a tumor diameter of <2 cm and those with a tumor diameter of >2 cm, and subsequently, their clinicopathological characteristics were compared.
Statistical analyses were performed using JMP for Windows version 10.0.0 (SAS Institute Japan, Minato, Japan). For continuous data with normal distribution, Student’s t-test was applied and is presented with mean and standardization. For variables with non-normal distribution, data were compared using the Wilcoxon signed-rank test. Fisher’s exact test was used to examine the associations between demographic parameters. Additionally, we calculated the receiver operating characteristic (ROC) curve for the volume index. A two-sided p-value of <0.05 was considered statistically significant for all statistical tests.
Results
Ninety-eight patients with cervical cancer who underwent radical hysterectomy were enrolled in the study; six patients were diagnosed with stage IIB cervical cancer and excluded. Thus, a total of 92 patients were included in the study. The patient characteristics are presented in Table I. Most patients had stage IB1-3 tumors (Table I).
Patient characteristics.
The incidence of lymph node metastasis and lymphovascular invasion was significantly higher in the group with a tumor diameter of >2 cm than in the group with a tumor diameter of <2 cm (Table II).
Clinicopathological characteristics of the study participants, classified according to pathological tumor diameter.
The sensitivity and specificity of preoperative MRI (Table III) for measuring the tumor diameter were 0.92 and 0.84, respectively. The calculated cut-off value was 2.60, whereas the volume index area under the ROC curve was 0.955, with a sensitivity of 0.92 and specificity of 0.93. We further evaluated the incidence of preoperative tumor diameter ≤2 cm and volume index <2.6 after positive pathological examinations (Table III), which showed a sensitivity of 0.92 and specificity of 0.93.
Comparison of tumor diameter on magnetic resonance imaging (MRI) and volume index based on postoperative pathology.
Discussion
Overall, the results of this study demonstrated that the volume index alone has a high specificity in early cervical cancer. Thus, the volume index does not need to be combined with the tumor diameter evaluated using MRI. Recently, the ConCerv trial showed that conservative therapy (simple hysterectomy or conization) is feasible for early cervical cancer with a tumor diameter of <2 cm (1). As treatment with conservative surgery, rather than radical hysterectomy is preferable, an accurate preoperative diagnosis for cervical cancer with a tumor diameter of <2 cm is essential to avoid unnecessarily traumatic procedures. The study protocol was revised due to the exclusion of patients with a postoperative diagnosis of cervical cancer, occult cancer, and recurrent cancer.
As minimally invasive surgery is not the gold-standard treatment for early cervical cancer, patients enrolled in related clinical trials should be selected carefully. While performing minimally invasive surgery for cervical cancer, a tumor diameter of >2 cm is considered an especially high-risk factor for recurrence and death (14, 15). A previous cohort study suggested that a tumor diameter of <2 cm poses a relatively lower risk (15) than a tumor diameter of >2 cm. Thus, the volume index may be useful for identifying suitable participants for clinical trials involving minimally invasive and conservative, non-radical surgeries.
The ongoing SHAPE trial is currently being conducted to compare simple and radical hysterectomies as treatment modalities for cervical cancer, many patients with cervical cancer tumors measuring <2 cm have been treated with a simple hysterectomy (16-18). This study has shown that these tumors have a low risk of lymph node metastasis and parametrial invasion (19, 20). While the results of the SHAPE trial are still pending, this trial has nevertheless shown that accurate preoperative evaluation of tumor diameter is essential. A test with high specificity and a low false-negative rate is crucial for determining the treatment strategy. In our study, the volume index had a high specificity, indicating its potential utility to address this need.
It is speculated that evaluation of tumor volume, a predictor of prognosis and metastasis of uterine corpus cancer, and three-dimensional imaging may lead to a low chance of error. As measured on multiple MRI images, tumor volume has also been identified as a risk factor for lymph node metastasis and lymphovascular invasion (21). Volume index can minimize errors and enhance clinical risk assessment.
Recently, it was suggested that not only T2-MRI, but also apparent diffusion coefficient (ADC) maps provide more information for determination of tumor volume (22). In this report, ADC maps were suggested to highlight areas hidden on T2 images, particularly for smaller volumes. In the future, we will commence a study on tumor volume of cervical cancer using ADC maps to determine appropriate indication for minimally invasive surgery and conservative surgery.
The primary limitation of our study was its retrospective observational design. In the future, prospective assessment studies should be conducted to validate our results.
In conclusion, our study demonstrated that the volume index is a highly specific diagnostic tool for early-stage cervical cancer. Specifically, we found that the tool is effective in preoperative diagnosis of pT1B1 cervical cancer with a low rate of false-negative results.
Footnotes
Authors’ Contributions
Ken Imai collected data and wrote the manuscript. Kenro Chikazawa performed the statistical analyses and checked the manuscript. Tomoyuki Kuwata and Ryo Konno checked and revised the manuscript.
Conflicts of Interest
K. Chikazawa received lecture honoraria from Ethicon (Tokyo, Japan), Terumo (Tokyo, Japan), and Chugai Pharmaceutical Co. (Tokyo, Japan). K. Imai received lecture honoraria from AstraZeneca (Tokyo, Japan). R. Konno received research funds from Yakult Pharmaceutical Industry Co. (Tokyo, Japan) and Chugai Pharmaceutical Co. (Tokyo, Japan), and lecture honoraria from Japan Vaccine Co. (Tokyo, Japan), MSD Japan (Tokyo, Japan), and Chugai Pharmaceutical Co. (Tokyo, Japan). T. Kuwata declares no conflict of interest. The funding sources had no role in this study’s design, practice, or analysis.
- Received March 22, 2023.
- Revision received April 9, 2023.
- Accepted April 14, 2023.
- Copyright © 2023 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
