Sentinel lymph node mapping for grade 1 endometrial cancer: Is it the answer to the surgical staging dilemma?

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Abstract

Objective

To describe the accuracy of SLN mapping in patients with a preoperative diagnosis of grade 1 endometrial cancer.

Methods

A prospective, non-randomized study of women with a preoperative diagnosis of endometrial cancer and clinical stage I disease was conducted. A subset analysis of patients with a preoperative diagnosis of grade 1 endometrial endometrioid cancer was performed. All patients had preoperative lymphoscintigraphy with Tc99m on the day of or day before surgery followed by an intraoperative injection of 2 cm3 of isosulfan or methylene blue dye deep into the cervix or both cervix and fundus. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and regional nodal dissection. Hot and/or blue nodes were labeled as SLNs and sent for histopathological analysis.

Results

Forty-two patients with a preoperative diagnosis of grade 1 endometrial carcinoma treated from 3/06 to 8/08 were identified. Twenty-five (60%) had laparoscopic surgery; 17 (40%) were treated by laparotomy. Preoperative lymphoscintigraphy visualized SLNs in 30 patients (71%); intraoperative localization of the SLN was possible in 36 patients (86%). A median of 3 SLNs (range, 1–14) and 14.5 non-SLNs (range, 4–55) were examined. In all, 4/36 (11%) had positive SLNs—3 seen on H&E and 1 as cytokeratin-positive cells on IHC. All node-positive cases were picked up by the SLN; there were no false-negative cases. The sensitivity of the SLN procedure in the 36 patients who had an SLN identified was 100%.

Conclusion

Sentinel lymph node mapping using a cervical injection with combined Tc and blue dye is feasible and accurate in patients with grade 1 endometrial cancer and may be a reasonable option for this select group of patients. Regional lymphadenectomy remains the gold standard in many practices, particularly for the approximately 15% of cases with failed SLN mapping.

Introduction

Comprehensive surgical staging for endometrial carcinoma is accepted by most gynecologic oncologists as the standard of care for the majority of patients with grade 2–3 endometrioid endometrial cancers as well as patients with clear cell and papillary serous tumors. However, these recommendations and the surgical treatment of patients with a preoperative diagnosis of grade 1 endometrioid endometrial cancer remain an area of significant debate, with a wide variation in the intraoperative management of the retroperitoneal nodes. Some patients are not surgically staged, some are comprehensively staged, and some are limitedly staged depending on the surgeon's intraoperative assessment of the tumor's risk for metastasis. The utility and value of intraoperative uterine examination by the surgeon or by a pathologist at frozen-section evaluation of depth of invasion and tumor size also remains variable among different institutions and practitioners; specifically, intraoperative frozen-section analysis for histologic grade and depth of myometrial invasion may not correlate well with final pathologic grade and stage [1].

Two significant contributors to the inconsistency in intraoperative management and universal acceptance of comprehensive surgical staging are the rarity of nodal metastases in true grade 1 endometrioid adenocarcinomas on final uterine pathology [2] and the excellent overall prognosis of women with a final diagnosis of grade 1 endometrial cancer [3]. In addition, there may be concerns about overtreating a potentially low-risk group of women who may have a prolonged survival, particularly when a comprehensive regional lymphadenectomy is performed, which may have long-term effects, including symptomatic leg lymphedema [4].

However, certain pathologic and clinical characteristics of women with a preoperative diagnosis of grade 1 endometrial cancer need further clarification. It is well documented that not all patients who present with a preoperative diagnosis of grade 1 endometrial carcinoma have a final diagnosis of grade 1 endometrial cancer; therefore, if not comprehensively staged, nearly 15% of patients deemed to have grade 1 lesions preoperatively will actually have higher grade lesions on final post-hysterectomy pathology. These patients would have otherwise been eligible and benefited from comprehensive staging [5]. In addition, identification of nodal metastasis, although rare, will likely have profound effects on postoperative management and adjuvant therapy. Therefore, our challenge is to identify a surgical technique that provides accurate staging information about nodal status while avoiding the potential for overtreating low-risk patients and undertreating patients with metastatic disease; in other words, identifying a more accurate surgical technique to stage endometrial cancer and avoid unnecessary morbidity.

The objectives of this manuscript were to describe our initial experience with sentinel lymph node (SLN) injections and mapping in women with a preoperative diagnosis of grade 1 endometrial cancer and to determine the sensitivity of this technique in an effort to suggest a new treatment algorithm for women presenting with grade 1 disease on endometrial biopsy or dilatation and curettage.

Section snippets

Methods

A prospective, non-randomized study of women presenting with a preoperative diagnosis of endometrial cancer with clinical stage I disease was conducted. This study reports on the subset of patients with preoperative grade 1 endometrioid adenocarcinoma. Other inclusion criteria included the following: a performance status of 0, 1, 2, or 3 by the Gynecologic Oncology Group criteria; and patients agreed to undergo total hysterectomy, removal of both adnexae, and bilateral regional lymphadenectomy

Results

Forty-two patients with a preoperative diagnosis of grade 1 endometrial endometrioid carcinoma treated between 3/06 and 8/08 were enrolled. Patients were diagnosed based on an office endometrial biopsy in 17 cases (40%) or dilatation and curettage in 25 cases (60%). Median age was 60.5 years (range, 34–82). Median body mass index (BMI) was 29.3 kg/m2 (range, 19–61 kg/m2). Twenty-five cases (60%) were performed by laparoscopic surgery, and 17 (40%) were treated by laparotomy. The selection of

Discussion

The search continues for a surgical technique that provides accurate pathologic information about the nodal status of patients with grade 1 endometrial cancer without overtreating potentially low-risk patients and undertreating patients with metastatic disease. SLN mapping in women with a preoperative diagnosis of grade 1 endometrial cancer may be an acceptable solution. This is usually a low-risk group for nodal metastasis; however, missing nodal disease in these select cases will likely have

Conflict of interest statement

  • 1.

    Nadeem R. Abu-Rustum, MD: no conflicts of interest to declare

  • 2.

    Fady-Khoury-Collado, MD: no conflicts of interest to declare

  • 3.

    Neeta Pandit-Taskar, MD: no conflicts of interest to declare

  • 4.

    Robert A. Soslow, MD: no conflicts of interest to declare

  • 5.

    Fanny Dao: no conflicts of interest to declare

  • 6.

    Yukio Sonoda, MD: Covidien, Consultant; Genzyme, Speaker's Bureau; Plasma Surgical, Research Support

  • 7.

    Douglas A. Levine, MD: no conflicts of interest to declare

  • 8.

    Carol L. Brown, MD: no conflicts of interest to declare

  • 9.

Acknowledgments

We would like to acknowledge and thank Lee K. Tan, M.D. for her contribution on the methodology of sentinel lymph node pathologic assessment and evaluation. We also would like to thank the gynecology service fellows and Physician assistants for their help in performing the radiolabeled injections.

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