Reassessment of the utility of frozen sections in endometrial cancer surgery using tumor diameter as an additional factor




Objective


The purpose of this study was to improve the reliability of frozen section with the use of tumor diameter (TD) as an additional factor and intraoperatively to identify a subgroup of early endometrial cancers that would not require lymphadenectomy.


Study Design


Data for 228 patients who underwent surgery with frozen section were analyzed retrospectively. Lymphadenectomy was performed in 86% of patients; the nodes were positive in 8%.


Results


The accuracy of frozen section for myometrial invasion, grade, and low-risk prediction significantly increased with decreasing TD ( P = .036) and was 98%, 95%, and 95%, respectively, when the TD was ≤3 cm. Patients with a TD of ≤2 cm and patients with a TD of 2-3 cm who had low-risk predictors had no nodal metastasis; patients with a TD of 2-3 cm who had intermediate-high risk predictors and a TD of >3 cm with any level of risk predictors were at risk of nodal metastases.


Conclusion


When the TD was ≤3 cm, the low-risk group that is defined by frozen section can be predicted accurately and safely to remain lymph-node metastasis free.


A simple abdominal hysterectomy and bilateral salpingo-oophorectomy procedure is the standard surgery for endometrial cancer; prognostic factors, such as histologic type, grade, myometrial invasion (MI), cervical invasion, adnexal involvement, and vascular space involvement, usually are evaluated by precise histologic examination with permanent section (PS) after the surgery. In addition, lymphadenectomy has long been adopted for endometrial cancer surgery, because patients with positive lymph nodes show decreased 5-year overall survival rates that range from 65-72%. Comprehensive lymphadenectomy has been considered necessary for both accurate staging and for determining whether adjuvant therapy should be administered.




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Regarding the therapeutic benefits of lymphadenectomy for patients with endometrial cancer, recent studies have shown that, in patients with an intermediate or high risk, a complete systematic lymphadenectomy in both the pelvic and paraaortic regions demonstrates a survival benefit. However, other recent prospective studies have not shown any evidence of survival benefit for pelvic lymphadenectomy in patients with low-risk, early-stage endometrial cancer. Based on these observations, it is accepted generally that patients with a low risk of lymph node involvement should avoid this procedure because of its adverse effects, such as lymphedema, lymphocysts, and infections.


In clinical practice, patients who are at low risk for lymph node metastasis are considered to be women without any risk factors on either preoperative or intraoperative findings. Previous studies have shown the depth of MI, tumor grade, and the presence of intraperitoneal spread to correlate independently with a high frequency of nodal metastasis. Mariani et al and Kamura et al demonstrated that tumor diameter (TD) is also correlated closely with the risk of nodal metastasis.


Although many approaches have been proposed to avoid lymphadenectomy that is based on the tumor grade and depth of MI on frozen section (FS), there was not always a high correlation between the FS diagnosis and final pathologic results. The significance of the intraoperative FS diagnosis in endometrial cancer therefore, remains to be elucidated. To date, there have not been any reports that have provided detailed information on the impact of TD on FS diagnosis. We hypothesized that TD might be a factor that affects the accuracy of intraoperative FS diagnosis and could be a breakthrough to improve the accuracy of the method.


In previous studies on FS, it was not possible to confirm whether FS diagnosis could safely identify a population that is free from lymph node metastasis, because the lymph nodes were not examined sufficiently. The frequency of lymph node sampling ranged from 27-76%. In the present study, lymph nodes were dissected more frequently than in previous studies. Lymph node dissection was performed in 86% of all patients in the present series, and investigation for the relationship between FS findings and lymph node metastasis was possible.


This is the first study to examine the impact of TD on the reliability of FS diagnosis for depth of invasion, grade, and low-risk prediction. Furthermore, these data were used to identify the true low-risk population that is free from lymph node metastases and can avoid lymphadenectomy.


Materials and Methods


Patient population


We analyzed the data that were obtained from 239 patients who were diagnosed initially with endometrial cancer without any evidence of extrauterine disease on preoperative imaging studies, such as magnetic resonance imaging or computed tomography. All patients underwent surgery at the National Kyushu Cancer Center between 1997 and 2007. Seven patients were excluded, because complete data were not available; 2 patients had ovarian cancer; and 2 patients could not be diagnosed because of the presence of either necrosis or myoma. Finally, 228 patients with endometrial cancer who underwent total extrafascial abdominal hysterectomy, bilateral salpingo-oophorectomy, and peritoneal washing were included in this study.


Lymph node assessment


Most patients underwent a bilateral pelvic lymphadenectomy and paraaortic sampling. Among all 228 patients with endometrial cancer, 176 patients (77.2%) underwent pelvic lymph node dissection plus paraaortic lymph node sampling, and 19 patients (8.3%) underwent only pelvic lymph node dissection/sampling. In 33 cases (14.5%), lymph node sampling was not performed because of medical complications, advanced age, or an intraoperative decision that was made by the surgeon. Histologic examination of the lymph nodes was possible in 195 of the cases (85.5%), and the nodes were positive in 16 cases (8.2%). The mean number of lymph nodes that were examined was 27.8 (range, 8–59) for pelvic lymph nodes and 8.4 (range, 1–23) for paraaortic node sampling.


Procedures used for FS


FS during surgery was done in the following manner: after removal of the uterus, a gynecologist cut the side walls and opened the uterine cavity. The longer axis of the macroscopically prominent part was measured immediately; then the vertical uterine incision (including the area of maximum TD) was examined. The samples were immediately frozen in liquid nitrogen, and 2 pathologists made the diagnosis. The histologic type, grade, vascular invasion, and depth of MI were assessed. When discrete lesions were present (such as those that extended to the opposite uterine wall), the sum of the diameter of each lesion was calculated.


The tumors were divided into 3 groups: ≤3 cm, 3-6 cm, and >6 cm, based on the longest axis of the tumor. The assessment of histologic MI was categorized into 3 groups: none, <50% and ≥50%. Serous, clear-cell carcinoma was classified as “other” when the tumors were graded. The patients with a low risk for nodal metastasis are defined as those having grade 1 or 2 endometrioid lesions, with no more than 50% MI, according to the findings of previous studies ; all other tumors were classified as intermediate-high risk.


The TD trend was analyzed with the Jonckheere-Terpstra analysis. Analysis with Cohen’s kappa coefficient was performed to evaluate the agreement between the FS and PS analyses. Cohen’s kappa coefficient is a statistical measure of interobserver agreement that may have been expected to occur by chance. It is generally considered that kappa values of 0.61-0.80 indicate substantial agreement; 0.81-1 indicates almost perfect agreement.


All statistical analyses were performed on a personal computer with the statistical package (SPSS for windows, version 11.0.1J; SPSS Inc, Chicago, IL).




Results


The characteristics of the 228 patients who were finally diagnosed as having endometrial cancer are listed in Table 1 . The average age was 56 years old, and International Federation of Gynecology and Obstetrics stage 1 was the most common stage. Preoperative imaging was obtained by magnetic resonance imaging in 46 patients and by computed tomography in all patients. The intraoperative measurements of fresh specimens ranged from 0–23 cm (mean, 35 mm). Almost all of the tumors were endometrioid adenocarcinoma, and approximately 50% of patients had grade 1 umors, based on their final histopathologic results. Lymph node metastases were identified in 16 patients, who all showed invasion of the myometrium on PS.



TABLE 1

Characteristics of 228 patients with early endometrial cancer
























































































Characteristic n (%)
Age, y
Mean ± SD 56 ± 10.7
FIGO stage
1 179 (78.5)
2 5 (2.2)
3 41 (18.0)
4 3 (1.3)
Tumor size, mm
Mean ± SD 35 ± 41.5
Histology
Endometrioid
No carcinoma 7 (3.1)
Grade 1 110 (48.2)
Grade 2 69 (30.3)
Grade 3 32 (14.0)
Non-endometrioid 10 (4.4)
Myometrial invasion
No carcinoma or no invasion 62 (27.2)
<1/2 112 (49.1)
≥1/2 54 (23.7)
Lymph node metastasis
Present 16 (7.0)
Absent 179 (78.5)
Not dissected 33 (14.5)
Risk group
Low risk a 149 (65.4)
Intermediate-high 79 (34.6)

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May 28, 2017 | Posted by in GYNECOLOGY | Comments Off on Reassessment of the utility of frozen sections in endometrial cancer surgery using tumor diameter as an additional factor

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