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Validity of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Pretreatment Evaluation of Patients With Cervical Carcinoma: A Retrospective Pathology-Matched Study

Dong, Yu MM*; Wang, Xiaoyun MBBS*; Wang, Yanan MM*; Liu, Yuan MM*; Zhang, Jiawen MM; Qian, Wenyan MM; Wu, Sufang MD, PhD*

International Journal of Gynecological Cancer: November 2014 - Volume 24 - Issue 9 - p 1642–1647
doi: 10.1097/IGC.0000000000000287
Cervical Cancer

Objective The aim of this study was to evaluate the validity of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for pretreatment evaluation of patients with cervical carcinoma.

Methods Retrospective evaluation of 63 patients, diagnosed with stage IA-IIA cervical carcinoma who underwent 18F-FDG PET/CT before surgery, was performed. Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios (LRs) of PET/CT for predicting the positive cervix, vagina, uterine body, and lymph node invasion at the surgical specimen was calculated.

Results Sensitivity, specificity, positive predictive value, and negative predictive value of the positive cervix invasion in PET/CT to detect positive surgical specimen were 88.2%, 75%, 93.8%, and 60%, respectively. The LR+ ratio was 3.5, and the LR− ratio was 0.2. Sensitivity, specificity, positive predictive value, and negative predictive value of the positive vagina invasion in PET/CT to detect positive surgical specimen were 100%, 70.97%, 5.3%, and 100%, respectively. The LR+ ratio was 3.4, and the LR− ratio was 0. Sensitivity, specificity, positive predictive value, and negative predictive value of the positive uterine body invasion in PET/CT to detect positive surgical specimen were 75%, 83.1%, 23.1%, and 98%, respectively. The LR+ ratio was 4.4, and the LR− ratio was 0.3. Sensitivity, specificity, positive predictive value, and negative predictive value of the positive lymph node invasion in PET/CT to detect positive surgical specimen were 87.5%, 78.4%, 38.9%, and 97.6%, respectively. The LR+ ratio was 4.1, and the LR− ratio was 0.2.

Conclusions The cervix invasion, negative uterine body invasion, and negative lymph node invasion are effective 18F-FDG PET/CT findings.

*Department of Obstetrics and Gynecology, Shanghai First People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China; †Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Shanghai, China; and ‡Department of Obstetrics and Gynecology, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, China.

Address correspondence and reprint requests to Sufang Wu, MD, PhD, Department of Obstetrics and Gynecology, Shanghai First People’s Hospital Affiliated to Shanghai Jiaotong University, No 650, Xinsongjiang Road, Songjiang District, Shanghai, China. E-mail: wsf_sfph@163.com.

Yu Dong and Xiaoyun Wang contributed equally to this study.

Supported in part by grants from the National Natural Science Foundation of China (NSFC no. 81201541), the grant (nos. 12PJD002 and 09411962500) form the Shanghai Science and Technology Committee, and the grant (no. 201002013) from the Science and Research Foundation for Public Welfare Industry of Ministry of Health of China.

The authors declare no conflicts of interest.

Received July 6, 2014

Received in revised form August 26, 2014

Accepted August 31, 2014

Cervical cancer is the second most common cancer in women and one of the major causes of death.1–4 Approximately 12,306 cases of invasive uterine cervical carcinoma are expected to be discovered, and approximately 4020 cases are expected to be dead in 2014.5

The most widely accepted staging system of cervical carcinoma is the International Federation of Gynecology and Obstetrics (FIGO). The FIGO staging system relies on physical examination, cervical biopsy, pathological review, and cone biopsy and does not include lymph nodal status. However, preoperative pelvic lymph node fluorodeoxyglucose (FDG) accumulation is significantly associated with cervical carcinoma relapse.6–8 Therefore, imagings that include computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) are often referential in treatment design.

For the past decade, 18F-FDG PET/CT has been increasingly accepted in gynecologic carcinomas because of its function to combine physiologic and anatomic findings and to scan the whole body, which will be helpful to detect both local and distant lesions.9 The PET/CT is useful in radiation therapy planning and in assessing the therapeutic efficacy for cervical carcinoma.10 Another article also suggests that PET/CT and MRI could be taken to estimate tumor response during concurrent chemoradiotherapy.11 The PET/CT and therapeutic innovations promise higher chances of survival of cervical carcinoma in the future.12

The FDG PET/CT is of great importance in the primary evaluation of cervical carcinoma, especially in the evaluation of lymph nodal status, which contributes to ensure proper staging and therapeutic strategy.13 Of the 8 patients with cervical cancer with FDG PET/CT positivity who underwent lymph node confirmation, 6 were negative.14

This study aimed to evaluate the validity of FDG PET/CT for pretreatment evaluation of patients with cervical carcinoma.

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METHODS

Between September 2009 and November 2012, 66 patients were referred to Shanghai First People’s Hospital for surgery with a diagnosis of stage IA-IIA cervical carcinoma and underwent 18F-FDG PET/CT using the Discovery STE 16 PET-CT System (General Electronic Medical System). The Discovery STE 16 PET-CT System has been developed to fulfill the new scanner requirements, such as better spatial resolution, high sensitivity, a larger patient port, and improvements in acquisition and econstruction features.15

Stages of cervical carcinoma were reported according to the criteria of FIGO: “I A is cervical carcinoma confined to cervix; I B is clinical visible lesion confined to the cervix or microscopic lesion greater than I A2; II A is cervical carcinoma invades beyond uterus without parametrial invasion.”

Patients with a history of chemotherapy before surgery (n = 3) were excluded. Thus, 63 of the 66 patients (95.5%) of the total cohort were eligible for evaluation.

Statistical analysis was performed mainly using SPSS 21. Descriptive statistics including the mean age of patients, mean interval between PET/CT and surgery, and frequency of each positive finding in different groups was performed. χ2 analysis and Fisher exact test were used.

We estimate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), negative likelihood ratio (LR−), positive LR (LR+), and 95% confidence intervals for those statistics in different groups.

A P < 0.5 was considered statistically significant.

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RESULTS

Sixty-three patients were included in the study. Table 1 shows the demographic data of the patients.

TABLE 1

TABLE 1

Of the 63 patients, 31 patients were tested for the presence of high-risk human papilloma virus infection: 28 were positive, and 2 were negative. Thirty patients (48%) underwent radical hysterectomy and pelvic lymph node dissection. Seven patients (11%) underwent radical hysterectomy, pelvic lymph node dissection, and para-aortic lymph node sampling. Seventeen patients (27%) underwent radical hysterectomy and pelvic lymph node dissection with preservation of 1 or both ovaries. Four patients (7%) underwent radical hysterectomy, pelvic lymph node dissection, and para-aortic lymph node sampling with preservation of 1 or both ovaries. Four patients (7%) underwent extrafascial hysterectomy. One patient was diagnosed with carcinoma of cervical stump and underwent radical trachelectomy and pelvic lymph node dissection. In these patients, the histologic diagnosis of the surgical specimen was recorded.

Seven patients (11.1%) had stage IA cervical carcinoma, 44 patients (69.8%) had stage IB cervical carcinoma, and 12 patients (19%) had stage IIA cervical carcinoma. Positive lymph node invasion in PET/CT was seen in 30.5% (n = 18) of the 59 patients who underwent pelvic lymph node dissection. Positive cervix and beyond cervix invasion in PET/CT were seen in 76.2% (n = 48) and 34.9% (n = 22) of the 63 patients, respectively.

Of the 63 patients with cervical carcinoma who underwent surgery, 48 showed positive cervix invasion in PET/CT. Sensitivity, specificity, PPV, and NPV of the positive cervix invasion to detect positive surgical specimen were 88.2%, 75%, 93.8%, and 60%, respectively. The LR+ ratio was 3.5, and the LR− ratio was 0.2 (Table 2).

TABLE 2

TABLE 2

A total of 88.2% of positive cervix invasion and 75% of negative cervix invasion in PET/CT were found in women with positive and negative surgery findings, respectively (P < 0.001).

Positive cervix invasion in PET/CT was present in 14.3%, 79.5%, and 100% of the patients with stage IA, IB, and IIA cervical carcinoma (P < 0.05) (Table 3).

TABLE 3

TABLE 3

Positive cervix invasion in PET/CT was present in 76%, 66.7%, and 100% of the patients with squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma (P = 0.79) (Table 4).

TABLE 4

TABLE 4

Of the 63 patients with cervical carcinoma who underwent surgery, 19 showed positive vagina invasion in PET/CT. Sensitivity, specificity, PPV, and NPV of the vagina invasion to detect positive surgical specimen were 100%, 70.97%, 5.3%, and 100%, respectively. The LR+ ratio was 3.4, and the LR− ratio was 0 (Table 2).

Of the 63 patients with cervical carcinoma who underwent surgery, 13 showed positive uterine body invasion in PET/CT. Sensitivity, specificity, PPV, and NPV of the uterine body invasion to detect positive surgical specimen were 75%, 83.1%, 23.1%, and 98%, respectively. The LR+ ratio was 4.4, and the LR− ratio was 0.3 (Table 2).

Of the 63 patients with cervical carcinoma who underwent surgery, none showed positive beyond-uterus invasion in PET/CT. One case showed positive vascular space invasion beyond uterus at surgical specimen.

A total of 100% of positive vagina invasion and 71% of negative vagina invasion in PET/CT were found in women with positive and negative surgery findings, respectively (P = 0.302).

A total of 75% of positive uterine body invasion and 83% of negative uterine body invasion in PET/CT were found in women with positive and negative surgery findings, respectively (P < 0.05).

Of the 59 patients with cervical carcinoma who underwent pelvic lymph node dissection, 18 showed positive lymph node invasion in PET/CT. Sensitivity, specificity, PPV, and NPV of the positive lymph node invasion to detect positive surgical specimen were 87.5%, 78.4%, 38.9%, and 97.6%, respectively. The LR+ ratio was 4.1, and the LR− ratio was 0.2 (Table 2).

A total of 87.5% of positive lymph node invasion and 78.4% of negative lymph node invasion in PET/CT was found in women with positive and negative surgery findings, respectively (P < 0.001).

Positive lymph node invasion in PET/CT was present in 0%, 34.9%, and 25% of the patients with stage IA, IB, and IIA cervical carcinomas (P = 0.44) (Table 3).

Positive lymph node invasion in PET/CT was present in 33%, 0%, and 50% of the patients with squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma, respectively (P = 0.24) (Table 4).

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DISCUSSION

Fifteen years ago, Sugawara et al16 demonstrated the feasibility of FDG PET imaging in patients with cervical carcinoma. Because not all patients had histological evidence of all lesions, the estimates were not that accurate. This article highlights the accuracy of the 18F-FDG PET/CT findings with all histological proofs of all lesions. Because positive PET/CT changes do not always match the histological abnormalities, we may help gynecologists to correctly diagnose and stage cervical carcinoma and guide treatment options and design.

The MRI is superior to CT for adjacent soft tissue involvement and evaluating tumor size, stromal invasion, and local and regional invasions of disease.17,18 The accuracy of MRI and CT is 90% to 100% and 60% to 70%, respectively.13 In the diagnosis of cervical carcinoma, T2-weighted MRI is recommended to evaluate local tumor invasion because of its high soft tissue contrast.19,20 The PET/CT and MRI are similar in measuring tumor volume.13 However, MRI only reveals the anatomic invasion of the carcinoma and does not reflect its biological changes.

As mentioned earlier, preoperative pelvic lymph node FDG accumulation is significantly associated with cervical carcinoma relapse.6–8 Despite of small tumor volume, the overall survival rate in patients with positive and negative lymph nodes is 50% and 90%, respectively.13 It is of great value to evaluate lymph node status before therapy.

The PET/CT owned higher specificity and lower sensitivity than diffusion weighted imaging (DWI). The sensitivity and specificity of DWI for detecting lymph node positivity were 83.3% and 51.2%, respectively. The sensitivity and specificity of PET/CT for detecting lymph node positivity were 38.9% and 96.3%, respectively. However, PET/CT and DWI were both not accurate enough to replace lymphadenectomy.21

The PET/CT seems to be more promising than CT in evaluating lymph node metastases.7,16 The sensitivity and specificity of PET/CT are depending on the stage of cervical cancer.22 In this study, sensitivity and specificity of the positive lymph node invasion in PET/CT to detect positive surgical specimen at stage IB were 83.3% and 72.97%, respectively. Sensitivity and specificity of the positive lymph node invasion in PET/CT to detect positive surgical specimen at stage IIA were 100% and 90%, respectively.

The cervix invasion, uterine body invasion, and lymph node invasion are effective 18F-FDG PET/CT findings and significantly associated with positive surgical specimens. A total of 88.2% of positive cervix invasion and 75% of negative cervix invasion in PET/CT were found in women with positive and negative surgery findings, respectively (P < 0.001). A total of 75% of positive uterine body invasion and 83% of negative uterine body invasion in PET/CT were found in women with positive and negative surgery findings, respectively (P < 0.05).A total of 87.5% of positive lymph node invasion and 78.4% of negative lymph node invasion in PET/CT were found in women with positive and negative surgery findings, respectively (P < 0.001).

According to predictive value, negative PET/CT result is more reliable in predicting vaginal, uterine body, and lymph node invasion; nevertheless, positive one is more valuable in predicting cervix invasion. The PPV and NPV of the positive cervix invasion in PET/CT to detect positive surgical specimen were 93.8% and 60%, respectively. The PPV and NPV of the vagina invasion in PET/CT to detect positive surgical specimen were 5.3% and 100%, respectively. The PPV and NPV of the uterine body invasion in PET/CT to detect positive surgical specimen were 23.1% and 98%, respectively. The PPV and NPV of the positive lymph node invasion in PET/CT to detect positive surgical specimen were 38.9% and 97.6%, respectively.

According to LRs, negative PET/CT result is more reliable in predicting cervix, vaginal, uterine body, and lymph node invasion. The LR+ and LR− ratios of the positive cervix invasion in PET/CT to detect positive surgical specimen were 3.5 and 0.2, respectively. The LR+ and LR− ratios of the vagina invasion in PET/CT to detect positive surgical specimen were 3.4 and 0, respectively. The LR+ and LR− ratios of the uterine body invasion in PET/CT to detect positive surgical specimen were 4.4 and 0.3, respectively. The LR+ and LR− ratios of the positive lymph node invasion in PET/CT to detect positive surgical specimen were 4.1 and 0.2, respectively.

The frequency of positive cervix invasion in PET/CT showed a correlation with stage. Positive cervix invasion was significantly less common in women with stage IA cervical carcinoma and more common in women with stage IIA cervical carcinoma. Positive cervix invasion in PET/CT was present in 14.3%, 79.5%, and 100% of the patients with stage IA, IB, and IIA cervical carcinomas (P < 0.05).The frequency of positive cervix and lymph node invasion did not show a correlation with stage. It is remarkable that, in patients with stage IA, 18F-FDG PET/CT is 100% correct in predicting cervical carcinoma and negative lymph node invasion at surgical specimen; in patients with stage IIA, 18F-FDG PET/CT is 100% correct in predicting cervical carcinoma and positive lymph node invasion at surgical specimen.

Although this study was limited in size and based on historical date only from 1 hospital, it has some decisive superiority. First, all 63 patients included in this study had histological proof, which is regarded as the golden criterion and the authentic diagnosis of disease. Second, cervical cancer is the second most common cancer in women. As mentioned before, the prevalence of cervical carcinoma will influence the predictive values of PET/CT for cervical carcinoma. Therefore, this research calculated the likelihoods for each positive PET/CT finding, which, unlike PPV and NPV, are independent of the prevalence of disease and also can be calculated for several levels.23 Likelihood between 1 and 5, between 5 and 10, and more than 10 indicate a small increase, moderate increase, and strong conclusive likelihood of disease, respectively. A negative likelihood between 0.5 and 1, between 0.1 and 0.2, and less than 0.1 indicate a minimal, moderate, and large decrease in the likelihood of disease, respectively.24 Third, it divides the patients into several groups according to stage and histology, which will help gynecologists to recognize when PET/CT results are more reliable on some level.

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Keywords:

18F-FDG PET/CT; Cervical carcinoma; Retrospective; Pathology matched

© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.