Magtrace® as Tracer for Sentinel Lymph Node Detection in Early Stage Epithelial Ovarian Cancer: a Pilot Study

Background EOC can metastasize through three different pathways: intraperitoneal (in the abdominal cavity), lymphogenous or haematogenous [5,6]. Concerning the lymphogenous spread, it is clear that lymphatic spread of EOC occurs mainly to the para-aortic lymph nodes. It is theorized that the tumour cells follow the lymph vessels that accompany the ovarian vessels in the infundibulopelvic ligament up to the upper para-aortic region and renal vein. Additionally, pelvic lymph node metastases are also frequently found. These tumour cells probably follow a different route, migrating via the para-uterine vessels in the broad ligament towards the uterine vessels and further on to the iliac vessels and lymph nodes. In some case reports, isolated inguinal node metastases are also described. The exact mechanism of this route of metastasis is still unclear, but the metastatic cells might follow the course of the round ligament towards the inguinal lymph nodes or follow the iliac vessels towards the femoral vessels.

According to the International Federation of Gynaecology and Obstetrics (FIGO), EOC with lymph node metastases is classified as FIGO stage IIIA1. This significant upstaging is reflected in the need for adjuvant treatment. While patients with cancer confined to the ovaries (FIGO stage I) do not require adjuvant chemotherapy, patients with EOC FIGO stage III require additional treatment. Therefore, the detection of lymph node metastases is of utmost importance in perceived early stage disease.

In case of a clinical early stage ovarian cancer, standard-of-care is a staging laparotomy including bilateral pelvic and para-aortal lymphadenectomy. There is 14% (range 6.1-29.6%) chance of finding lymph node metastases . The incidence is higher in the grade 3 tumours (20.0%) and the serous histological subtype (23.3%). Whereas in grade 1 and mucinous tumours this is respectively 4.0% and 2.6%. By removing a greater number of lymph nodes, the detection rate for metastases rises . Although complete pelvic and para-aortic lymphadenectomy is standard-of-care, radical lymphadenectomy has been associated with serious morbidity and this is a major reason for the difference in the extent of lymph node dissection between centres.

By resecting only the SLN, significant reduction of morbidity and mortality can be obtained in comparison with the standard-of-care. SLN surgery is based on the concept that, if the SLN has no malignant cells, the likelihood that other lymph nodes are affected is reduces to almost non-existent. This means that, at least theoretically, a radical lymphadenectomy could be omitted and thus the associated morbidity and potential mortality. The SLN technique has been proven to be effective in other cancers such as breast cancer and malignant melanoma. In the gynaecological field it has been shown to be effective in vulvar cancer. Several SLN studies have been conducted in patients with ovarian cancer with promising results, as summarized in Table 1.

Rationale As stated, the goal of utilizing SLN in early-stage EOC surgery is to reduce patient morbidity while obtaining optimal oncological outcomes. By resecting only the SLN, the patients would be spared from radical lymphadenectomy, reducing short and long-term complications.