ObjectiveSentinel lymph node mapping has emerged as an alternative to lymphadenectomy in evaluating the lymph node status in endometrial cancer. Several pathological methods to examine the sentinel lymph node are applied internationally. The aim of this study was to determine the value of ultrastaging and to assess the ultrastaging method with the highest detection rate of metastases.MethodsA systematic review was conducted. Inclusion criteria were: pathologically-confirmed endometrial cancer with sentinel lymph node mapping, report of the histological outcomes, metastases found by hematoxylin and eosin staining and metastases found by ultrastaging were separately mentioned, and description of the ultrastaging method. The primary outcome was the detection of metastases found by ultrastaging that were not detected by routine hematoxylin and eosin staining. The secondary outcome was the difference in detection rate of metastases between several ultrastaging methods. Random effects meta-analyses were conducted.ResultsFifteen studies were selected, including 2259 patients. Sentinel lymph nodes were examined by routine hematoxylin and eosin staining. Subsequently, multiple ultrastaging methods were used, with differences in macroscopic slicing (bread-loaf/longitudinal), number of microscopic slides, and distance between slides, but all used immunohistochemistry. A positive sentinel lymph node was found in 14% of patients. In 37% of these, this was detected only by ultrastaging. Using more ultrastaging slides did not result in a higher detection rate. Bread-loaf slicing led to a higher detection rate compared with longitudinal slicing (mean detection rates 53% and 33%, respectively).ConclusionPathological ultrastaging after routine hematoxylin and eosin staining in endometrial cancer patients has led to an increased detection rate of sentinel lymph node metastases. Different ultrastaging methods are used, with a preference for bread-loaf slicing. However, due to the large heterogeneity of the studies, assessing which ultrastaging method has the highest detection rate of sentinel lymph node metastases was not possible.

Objective: Peritoneal metastases (PM) are a challenge in gynecological cancers, but its appearance has never been described in a population-based study. Therefore, we describe the incidence of PM and identify predictors that increase the probability of peritoneal spread. Methods: All ovarian, endometrial and cervical cancer patients diagnosed in the Netherlands between 1989 and 2015 were identified from the Netherlands Cancer Registry and stratified for PM. Crude and age-adjusted incidence over time was calculated. Independent predictors for PM were identified using uni-and multivariable analyses. Results: The 94,981 patients were diagnosed with ovarian, endometrial or cervical cancer and respectively 61%, 2% and 1% presented with PM. Predictors for PM in ovarian cancer were: age between 50 and 74 years (odds ratio [OR]=1.19; 95% confidence interval [CI]=1.08-1.32), other distant metastases (OR=1.25; 95% CI=1.10-1.41), poor differentiation grade (OR=2.00; 95% CI=1.73-2.32) and serous histology. Predictors in endometrial cancer were lymph node metastases (OR=2.32; 95% CI=1.65-3.26), other distant metastases (OR=1.38; 95% CI=1.08-1.77), high-grade tumors (OR=1.95; 95% CI=1.38-2.76) and clear cell (OR=1.49; 95% CI=1.04-2.13) or serous histology (OR=2.71; 95% CI=2.15-3.42). In cervical cancer, the risk is higher in adenocarcinoma than in squamous cell carcinoma (OR=4.92; 95% CI=3.11-7.79). Conclusion: PM are frequently seen in patients with ovarian cancer. In endometrial and cervical cancer PM are rare. Histological subtype was the strongest predictive factor for PM in all 3 cancers. Better understanding of predictive factors for PM and thus the biological behavior is of paramount importance.

Sentinel lymph node mapping is the most cost-effective strategy for patients with low-and intermediate-risk endometrial cancer • Sentinel lymph node mapping is more costly than risk factor assessment, but the costs stay below the willingness-to-pay threshold. • Sentinel lymph node mapping is dominant compared to lymph node dissection.

Objective The aim of this study was to assess the SLN detection rate in presumed early stage, low- and intermediate-risk endometrial cancers, the incidence of SLN metastases, and the negative predictive value of SLN mapping performed with indocyanine green (ICG). Methods A systematic review with meta-analyses was conducted. Study inclusion criteria were A) low- and intermediate-risk endometrial cancer, B) the use of ICG per cervical injection; C) a minimum of twenty included patients per study. To assess the negative predictive value of SLN mapping, D) a subsequent lymphadenectomy was an additional inclusion criterion. Results Fourteen studies were selected, involving 2,117 patients. The overall and bilateral SLN detection rates were 95.6% (95% confidence interval [CI]=92.4%–97.9%) and 76.5% (95% CI=68.1%–84.0%), respectively. The incidence of SLN metastases was 9.6% (95% CI=5.1%–15.2%) in patients with grade 1–2 endometrial cancer and 11.8% (95% CI=8.1%–16.1%) in patients with grade 1–3 endometrial cancer. The negative predictive value of SLN mapping was 100% (95% CI=98.8%–100%) in studies that included grade 1–2 endometrial cancer and 99.2% (95% CI=97.9%–99.9%) in studies that also included grade 3. Conclusion SLN mapping with ICG is feasible with a high detection rate and negative predictive value in low- and intermediate-risk endometrial cancers. Given the incidence of SLN metastases is approximately 10% in those patients, SLN mapping may lead to stage shifting with potential therapeutic consequences. Given the high negative predictive value with SLN mapping, routine lymphadenectomy should be omitted in low- and intermediate-risk endometrial cancer.

ObjectiveSentinel lymph node (SLN) mapping in endometrial cancer is gaining ground. However, patient views on this new technique are unknown. The aim of this study was to determine factors important to patients and gynecologists when considering SLN mapping in low- and intermediate-risk endometrial cancer.MethodsWe performed a vignette study. Patients who underwent a total hysterectomy for low- or intermediate-risk endometrial cancer between 2012 and 2015 were invited. Dutch gynecologists specializing in gynecologic oncology were also invited. We based the selection for attributes in the vignettes on literature and interviews: risk of complications of SLN mapping; chance of finding a metastasis; survival gain; risk of complications after radiotherapy; operation time; and hospital of surgery (travel time). We developed a questionnaire with 18 hypothetical scenarios. Each attribute level varied and for each scenario, participants were asked how strongly they would prefer SLN on a scale from 1 to 7. The strength of preference for each scenario was analyzed using linear mixed effects models.ResultsA total of 38% of patients (41/108) and 33% of gynecologists (42/126) participated in the study. Overall, they had a preference for SLN. The mean preference for patients was 4.29 (95% CI 3.72 to 4.85) and 4.39 (95% CI 3.99 to 4.78) for gynecologists. Patients’ preferences increased from 3.4 in the case of no survival gain to 4.9 in the case of 3-year survival gain (P<0.05) and it decreased when travel time increased to >60 min (−0.4, P=0.024), or with an increased risk of complications after adjuvant radiotherapy (−0.6, P=0.002). For gynecologists all attributes except travel time were important.ConclusionsOverall, patients and gynecologists were in favor of SLN mapping in low- and intermediate-risk endometrial cancer. Most important to patients were survival gain, travel time, and complication risk after adjuvant radiotherapy. These preferences should be taken into account when counseling about SLN mapping.

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The aim was to investigate the incidence of sentinel lymph node (SLN) metastases and the contribution of SLN mapping in presumed low- and intermediate-risk endometrial cancer (EC). A multicenter, prospective cohort study in presumed low- and intermediate-risk EC patients was performed. Patients underwent SLN mapping using cervical injections of indocyanine green and a minimally invasive hysterectomy with bilateral salpingo-oophorectomy. The primary outcome was the incidence of SLN metastases, leading to adjusted adjuvant treatment. Secondary outcomes were the SLN detection rate and the occurrence of complications. Descriptive statistics and univariate general linear model analyses were used. A total of 152 patients were enrolled, with overall and bilateral SLN detection rates of 91% and 61%, respectively. At final histology, 78.9% of patients (n = 120) had truly low- and intermediate-risk EC. Macro- and micro-metastases were present in 11.2% (n = 17/152), and three patients had isolated tumor cells (2.0%). Nine patients (5.9%) had addition of adjuvant radiotherapy based on SLN metastases only. In 2.0% of patients with high-risk disease, adjuvant therapy was more limited due to negative SLNs. This study emphasizes the importance of SLN mapping in presumed early-stage, grade 1 and 2 EC, leading to individualized adjuvant management, resulting in less undertreatment and overtreatment.