Summary Background Retrospective single-centre series have shown the feasibility of sentinel lymph-node (SLN) identification in endometrial cancer. We did a prospective, multicentre cohort study to assess the detection rate and diagnostic accuracy of the SLN procedure in predicting the pathological pelvic-node status in patients with early stage endometrial cancer. Methods Patients with International Federation of Gynecology and Obstetrics (FIGO) stage I–II endometrial cancer had pelvic SLN assessment via cervical dual injection (with technetium and patent blue), and systematic pelvic-node dissection. All lymph nodes were histopathologically examined and SLNs were serial sectioned and examined by immunochemistry. The primary endpoint was estimation of the negative predictive value (NPV) of sentinel-node biopsy per hemipelvis. This is an ongoing study for which recruitment has ended. The study is registered with ClinicalTrials.gov, number NCT00987051. Findings From July 5, 2007, to Aug 4, 2009, 133 patients were enrolled at nine centres in France. No complications occurred after injection of technetium colloid and no anaphylactic reactions were noted after patent blue injection. No surgical complications were reported during SLN biopsy, including procedures that involved conversion to open surgery. At least one SLN was detected in 111 of the 125 eligible patients. 19 of 111 (17%) had pelvic-lymph-node metastases. Five of 111 patients (5%) had an associated SLN in the para-aortic area. Considering the hemipelvis as the unit of analysis, NPV was 100% (95% CI 95–100) and sensitivity 100% (63–100). Considering the patient as the unit of analysis, three patients had false-negative results (two had metastatic nodes in the contralateral pelvic area and one in the para-aortic area), giving an NPV of 97% (95% CI 91–99) and sensitivity of 84% (62–95). All three of these patients had type 2 endometrial cancer. Immunohistochemistry and serial sectioning detected metastases undiagnosed by conventional histology in nine of 111 (8%) patients with detected SLNs, representing nine of the 19 patients (47%) with metastases. SLN biopsy upstaged 10% of patients with low-risk and 15% of those with intermediate-risk endometrial cancer. Interpretation SLN biopsy with cervical dual labelling could be a trade-off between systematic lymphadenectomy and no dissection at all in patients with endometrial cancer of low or intermediate risk. Moreover, our study suggests that SLN biopsy could provide important data to tailor adjuvant therapy. Funding Direction Interregionale de Recherche Clinique, Ile-de-France, Assistance Publique–Hopitaux de Paris.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(11)70070-5.pdf

Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO)

Sentinel lymph node biopsy in the management of early-stage cervical carcinoma.

Lymph node metastases is a recognized prognostic factor in women with cervical cancer. However, there is a need for consensual histological definition of micrometastases in this indication which could give rise to a classification system similar to that used in breast cancer. We thus conducted a MEDLINE and EMBASE database analysis to evaluate the concept of micrometastases in cervical cancer. Retrospective studies place the incidence of micrometastasis between 1.5 and 15% depending on the technique used to evaluate lymph node status. Sentinel lymph node biopsy with serial sectioning and immunohistochemical analysis appears to be the most accurate micrometastases detection technique. The value of RT-PCR in micrometastases detection remains to be clarified by further studies. From a clinical view point, few data are available to support the prognostic relevance of micrometastases. However, case control and longitudinal studies have underlined the risk of recurrence in women with micrometastases, raising the issue of a revision of adjuvant therapy indications in this specific population.

Sentinel lymph node biopsy in gynaecological cancers: The importance of micrometastases in cervical cancer

Although it does not have a long history of sentinel node evaluation (SLN) in female genital system cancers, there is a growing number of promising study results, despite the presence of some aspects that need to be considered and developed. It has been most commonly used in vulvar and uterine cervivcal cancer in gynecological oncology. According to these studies, almost all of which are prospective, particularly in cases where Technetium-labeled nanocolloid is used, sentinel node detection rate sensitivity and specificity has been reported to be 100%, except for a few cases. In the studies on cervical cancer, sentinel node detection rates have been reported around 80–86%, a little lower than those in vulva cancer, and negative predictive value has been reported about 99%. It is relatively new in endometrial cancer, where its detection rate varies between 50 and 80%. Studies about vulvar melanoma and vaginal cancers are generally case reports. Although it has not been supported with multicenter randomized and controlled studies including larger case series, study results reported by various centers around the world are harmonious and mutually supportive particularly in vulva cancer, and cervix cancer. Even though it does not seem possible to replace the traditional approaches in these two cancers, it is still a serious alternative for the future. We believe that it is important to increase and support the studies that will strengthen the weaknesses of the method, among which there are detection of micrometastases and increasing detection rates, and render it usable in routine clinical practice.

/pdf/lymphatic-mapping-and-sentinel-node-biopsy-in-gynecological-181schhvs5.pdf

Lymphatic mapping and sentinel node biopsy in gynecological cancers: a critical review of the literature

Treatment of patients with vulvar cancer is challenging for gynaecologic oncologists. Owing to the localization in a sensitive area, surgical radicality and the indication for adjuvant treatment have to be balanced with psychosocial aspects to treat patients adequately. Clinical management is therefore highly dependent on the tumour stage. For patients with early-stage disease (FIGO I–II) therapy mainly concentrates on surgery with resection of the primary tumour and staging of the groin lymph nodes. In intermediate-stage vulvar cancer (FIGO III), advanced disease is expressed by affected inguinofemoral lymph nodes bringing radical lymphadenectomy and adjuvant therapy as well as radiation or chemoradiation into the focus of treatment. For locally advanced or metastatic vulvar cancer (FIGO IV) neoadjuvant or definitive chemoradiation has to be considered besides surgery. Owing to the low incidence of the disease, the level of evidence for different treatment modalities is poor. This review therefore puts different recommendations of clinical management in context and highlights the need for future trials.

/pdf/management-of-patients-with-vulvar-cancer-a-perspective-5aek2jq8uo.pdf

Management of patients with vulvar cancer: a perspective review according to tumour stage.

Vulvar cancer is an uncommon but devastating disease. In addition to radical vulvectomy, most patients require inguinofemoral lymphadenectomy, which often results in wound infection, wound breakdown, and chronic lymphedema. In the past, the gold standard for early lesions was radical vulvectomy with complete bilateral inguinal-femoral lymphadenectomy. This resulted in a low rate of recurrence but devastating disfigurement and high complication rates. Because only approximately 20% of patients with vulvar cancer have positive lymph nodes upon presentation, the traditional approach of inguinal-femoral lymphadenectomy for all patients resulted in many patients undergoing a morbid procedure without any real benefit. Sentinel node dissection, by removing only the nodes with the highest risk of containing metastases, offers a much less morbid alternative. In addition, because only one or two lymph nodes are removed, these can be subjected to a more thorough histopathologic analysis than conventional complete lymphadenectomy. This involves serial sectioning and immunohistochemical staining for cytokeratin antigen. Very small metastases, termed micrometastases, can be detected in this fashion. Therefore, sentinel node dissection with serial sectioning and immunohistochemical staining potentially offers a more accurate assessment of the regional nodes with less morbidity. Patients with positive sentinel nodes may then undergo additional therapy. Patients with negative sentinel nodes are theoretically at very low risk for metastases and should not require any additional treatment.

Keith Y Terada

Papers

Sentinel node dissection in vulvar cancer.