Utility of PRAME Immunohistochemistry in the Detection of Subtle Melanoma Microsatellites.

ABSTRACT: Microsatellitosis is well established as a prognostic factor in malignant melanoma. Its identification leads to subsequent upstaging with implications for further management. We describe 6 cases in which immunohistochemical staining for PReferentially expressed Antigen in MElanoma facilitated detection of small foci of micrometastasis on scanning magnification, which may be potentially missed in routine sections.

Analysis of false reasons based on the artificial intelligence RRCART model to identify frozen sections of lymph nodes in breast cancer.

BACKGROUND: Breast cancer is the most common malignant tumor in the world. Intraoperative frozen section of sentinel lymph nodes is an important basis for determining whether axillary lymph node dissection is required for breast cancer surgery. We propose an RRCART model based on a deep-learning network to identify metastases in 2362 frozen sections and count the wrongly identified sections and the associated reasons. The purpose is to summarize the factors that affect the accuracy of the artificial intelligence model and propose corresponding solutions. METHODS: We took the pathological diagnosis of senior pathologists as the gold standard and identified errors. The pathologists and artificial intelligence engineers jointly read the images and heatmaps to determine the locations of the identified errors on sections, and the pathologists found the reasons (false reasons) for the errors. Through NVivo 12 Plus, qualitative analysis of word frequency analysis and nodal analysis was performed on the error reasons, and the top-down error reason framework of "artificial intelligence RRCART model to identify frozen sections of breast cancer lymph nodes" was constructed based on the importance of false reasons. RESULTS: There were 101 incorrectly identified sections in 2362 slides, including 42 false negatives and 59 false positives. Through NVivo 12 Plus software, the error causes were node-coded, and finally, 2 parent nodes (high-frequency error, low-frequency error) and 5 child nodes (section quality, normal lymph node structure, secondary reaction of lymph nodes, micrometastasis, and special growth pattern of tumor) were obtained; among them, the error of highest frequency was that caused by normal lymph node structure, with a total of 45 cases (44.55%), followed by micrometastasis, which occurred in 30 cases (29.70%). CONCLUSIONS: The causes of identification errors in examination of sentinel lymph node frozen sections by artificial intelligence are, in descending order of influence, normal lymph node structure, micrometastases, section quality, special tumor growth patterns and secondary lymph node reactions. In this study, by constructing an artificial intelligence model to identify the error causes of frozen sections of lymph nodes in breast cancer and by analyzing the model in detail, we found that poor quality of slices was the preproblem of many identification errors, which can lead to other errors, such as unclear recognition of lymph node structure by computer. Therefore, we believe that the process of artificial intelligence pathological diagnosis should be optimized, and the quality control of the pathological sections included in the artificial intelligence reading should be carried out first to exclude the influence of poor section quality on the computer model. For cases of micrometastasis, we suggest that by differentiating slices into high- and low-confidence groups, low-confidence micrometastatic slices can be separated for manual identification. The normal lymph node structure can be improved by adding samples and training the model in a targeted manner.

In Situ Albumin-Hitchhiking NIR-II Probes for Accurate Detection of Micrometastases.

Tumor metastasis remains the primary cause of treatment failure in cancer patients, and the high-sensitivity preoperative and intraoperative detection of occult micrometastases continues to pose a notorious challenge. Therefore, we have designed an in situ albumin-hitchhiking near-infrared window II (NIR-II) fluorescence probe, IR1080, for the precise detection of micrometastases and subsequent fluorescence image-guided surgery. IR1080 rapidly covalently conjugates with albumin in plasma, resulting in a stronger fluorescence brightness upon binding. Moreover, the albumin-hitchhiked IR1080 has a high affinity for secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein that is overexpressed in micrometastases. The interaction between SPARC and IR1080-hitchhiked albumin enhances IR1080's capacity to track and anchor micrometastases, leading to a high detection rate and margin delineation ability, as well as a high tumor-to-normal tissue ratio. Therefore, IR1080 represents a highly efficient strategy for the diagnosis and image-guided resection surgery of micrometastases.

Evaluation of the one-step nucleic acid amplification method for rapid detection of lymph node metastases in endometrial cancer: prospective, multicenter, comparative study.

OBJECTIVE: To evaluate the diagnostic performance of the one-step nucleic acid amplification (OSNA) method for the detection of sentinel lymph node (SLN) metastases in women with apparent early-stage endometrial cancer compared with standard ultrastaging. METHODS: Prospective, multicentric, interventional study. Patients with apparent early-stage endometrial cancer who underwent primary surgical staging with SLN mapping were included. SLNs were serially sectioned with 2 mm slices perpendicular to the longest axis of the node: the odd slices were submitted to ultrastaging, whereas the even slices were submitted to the OSNA analysis. Diagnostic performance was calculated taking ultrastaging as referral standard. RESULTS: Three-hundred and sixteen patients with 668 SLNs were included. OSNA assay detected 22 (3.3%) positive SLNs, of which 17 (2.5%) were micrometastases and 5 (0.7%) macrometastases, whereas ultrastaging detected 24 (3.6%) positive SLNs, of which 15 (2.2%) were micrometastases and 9 (1.3%) macrometastases (p=0.48). Regarding negative SLNs, OSNA detected 646 (96.7%) negative nodes, including 8 (1.2%) isolated tumor cells, while ultrastaging detected 644 (96.4%) negative nodes with 26 (3.9%) isolated tumor cells. Specificity of OSNA was 98.4% (95% CI 97.5 to 99.4), accuracy was 96.7% (95% CI 95.4 to 98.1), sensitivity was 50% (95% CI 30.0 to 70.0), while negative predictive value was 98.1% (95% CI 97.1 to 99.2). Discordant results were found in 22 SLNs (3.3%) corresponding to 20 patients (6.3%). These were 10 (1.5%) false-positive SLNs (all micrometastases): one (0.1%) of these was a benign epithelial inclusion at ultrastaging. There were 12 (1.8%) false-negative SLNs of OSNA, of which 9 (1.3%) were micrometastases and 3 (0.5%) macrometastases. Overall, 17/668 (2.5%) benign epithelial inclusions were detected at ultrastaging. CONCLUSION: The OSNA method had high specificity and high accuracy in detecting SLN metastasis in apparent early-stage endometrial cancer. The advantage of the OSNA method could be represented as the possibility to analyze the entire lymph node thus eliminating sampling bias.

Septin 9 methylation analysis of lymph node micrometastases for predicting relapse of colorectal cancer.

BACKGROUND: Molecular markers for the detection of lymph node micrometastases of malignant tumors have been extensively investigated. However, epigenetic signatures have rarely been reported for identification of metastatic lymph nodes and disease relapse. Septin 9 is the most frequently reported hypermethylated gene in colorectal cancer (CRC). This study aimed to assess the clinical relevance of Septin 9 methylation in regional lymph nodes in recurrence/metastases of CRC. METHODS: We analyzed Septin 9 methylation of DNA from resected lymph nodes in 75 CRC patients with or without tumor recurrence using quantitative methylation-sensitive PCR (qMS-PCR). RESULTS: Of the 30 histologically negative lymph node CRC patients without recurrence (group 1), methylated Septin 9 was detected in 3 (10 %) cases. The positivity rate of methylated Septin 9 in group 2 containing 30 histologically node-negative CRC patients with recurrence was 30 % (9/30). For group 3, lymphatic invasion as well as tumor recurrence, 11 (73 %) out of 15 subjects had Septin 9 methylation-positive lymph nodes. Moreover, patients in group 3 had a higher level of methylated Septin 9 compared to subjects in group 1 and group 2 (p < 0.05). In addition, CRC patients with Septin 9 methylation in lymph nodes had significantly reduced survival (Log-rank P < 0.0001). CONCLUSION: Our data support the predictive role of Septin 9 methylation analysis of lymph node micrometastases for tumor relapse after surgery.

Emerging Technologies for the Detection of Cancer Micrometastasis.

The most efficient way to treat tumors is through surgery. However, many cancer patients have a poor prognosis even when they undergo radical excision at an early stage. Micrometastasis is one of the most critical factors that induced this situation. Undetected micrometastasis can lead to the failure of initial treatment. Therefore, preoperative and intraoperative detection of micrometastasis could have a significant clinical influence on the prognosis and optimal therapy for cancer patients. Additionally, to achieve this goal, researchers have aimed to create more effective detection technologies. Herein, we classify the currently reported micrometastasis detection technologies, introduce some representative samples for each technology, including the limitations, and provide future directions to overcome the limitations.

Prognostic Value of Mesorectal Lymph Node Micrometastases in ypN0 Rectal Cancer After Chemoradiation.

INTRODUCTION: More than 25% of patients with node-negative colorectal cancer experience a recurrent disease even after curative surgery. This suggests the existence and oncologic influence of micrometastasis in regional lymph nodes or in distant organs. The objective of this study was to identify mesorectal lymph node micrometastases using an immunohistochemical analysis and to determine its prognostic value in node-negative rectal cancer after neoadjuvant chemoradiation. MATERIALS AND METHODS: A total of 91 patients who received preoperative chemoradiation and radical resection for rectal cancer were included. Based on conventional hematoxylin and eosin staining, all patients had a node-negative disease. Mesorectal lymph nodes from resected specimens were re-evaluated to detect micrometastases by immunohistochemistry using anticytokeratin antibody AE1/AE3. The clinicopathologic data were collected from a prospectively maintained database of colorectal cancer patients and analyzed retrospectively. RESULTS: Micrometastases of mesorectal lymph nodes were detected in nine patients (9.9%). The three-year overall survival was similar regardless of micrometastasis (88.9% in the positive group versus 90.7% in the negative group, P = 0.681); however, the three-year disease-free survival was significantly poorer in the patients with micrometastases (40.0% versus 84.2%, P = 0.001). In the multivariate analysis, the advanced pT category (ypT3/T4 versus ypT0: hazard ratio [HR] 10.477, 95% confidence interval [CI] 1.102-99.594, P = 0.041) and micrometastases in mesorectal lymph nodes (HR 5.655, 95% CI 1.837-17.409, P = 0.003) were independent prognostic factors for disease-free survival. CONCLUSIONS: In node-negative rectal cancer after preoperative chemoradiation, immunohistochemically detected micrometastases of mesorectal lymph nodes were significantly correlated with poor disease-free survival.

Curative-intent Metastasis-directed Therapies for Molecularly-defined Oligorecurrent Prostate Cancer: A Prospective Phase II Trial Testing the Oligometastasis Hypothesis.

BACKGROUND: The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches. OBJECTIVE: We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT). DESIGN/SETTING/PARTICIPANTS: Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible. INTERVENTIONS: All patients underwent [18F]DCFPyL PET-MR/CT. Patients with molecularly-defined oligorecurrent-PCa had MDT (stereotactic ablative body radiotherapy [SABR] or surgery) without HT. OUTCOME MEASUREMENTS/STATISTICAL ANALYSIS: Primary endpoint was biochemical response (complete, i.e. biochemical 'no evidence of disease' [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon's two-stage design was employed (null and alternate hypotheses <5% and >20% response rate, respectively), with α and ß of 0.1. RESULTS: Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed. CONCLUSIONS: PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/- systemic agents can expand the curative therapeutic armamentarium for PCa. PATIENT SUMMARY: We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.

Clinical effect of the pathological axillary assessment method in breast cancer without clinical nodal metastasis.

BACKGROUND: This study aimed to assess the clinical effect of the pathological axillary assessment method in breast cancer without clinical lymph node metastasis. METHODS: Data of patients with clinically node-negative breast cancer were retrospectively reviewed. The study period was divided into early (January 2000-July 2007) and late (August 2007-December 2014) periods based on the pathological assessment method used (single-sectional and detailed multi-sectional lymph node processing). In the late period, lymph nodes were evaluated at six levels including immunohistochemistry on each 1.5-2 mm interval section. The axillary diagnostic accuracy and role of chemotherapy were assessed. RESULTS: In 1698 patients, 27 isolated tumor cells (ITCs), 39 micrometastases, and 205 macrometastases were noted. The sensitivity for pathological N0 diagnosis was dependent on clinical T stage, Tis (97.8%), T1 (83.0%), T2 (74.2%), T3 (54.5%), and T4 (63.6%). ITCs and micrometastases were detected only in the late period, and 84.7% and 91.6% of cases in the early and late period, respectively, did not have macrometastases. The 5-year disease-free interval (DFI) rates were 95.2% in node-negative cases, 98.4% in ITCs/micrometastases, and 91.4% in macrometastases (P < 0.001). In multivariate analysis, the predictor for DFI was estrogen receptor negativity (P = 0.013). Chemotherapy did not improve DFI in patients with node-positive breast cancer. CONCLUSIONS: The detailed multi-sectional pathological assessment of axillary lymph nodes detected ITCs and micrometastases. Implementation of chemotherapy should not be based on the minimal nodal metastasis and this type of serially nodal sectioned processing had little clinical significance.

The Advantage of Pinpoint Camera System With Indocyanine Green for Sentinel Lymph Node Micrometastasis Detection in Low Risk Endometrial Cancer.

BACKGROUND/AIM: This report outlines our experience in the management of 10 cases of low-risk endometrial cancer with Indocyanine Green for sentinel lymph node (SLN) mapping using the Pinpoint 30-degree 4K S1 SPY real-time camera system (Stryker). This system offers simultaneous, real-time, high-definition white light and fluorescence imaging through a single laparoscope, without the need to change camera filters. PATIENTS AND METHODS: In our retrospective case series we included all endometrioid endometrial cancers of grade G1 and pre-operative radiological staging FIGO 1A reported on magnetic resonance imaging (MRI) that were treated laparoscopically from October 2019 to April 2020. RESULTS: Bilateral sentinel lymph node excision was achieved in 9 out of 10 cases. In one patient, one sentinel lymph node featuring a micrometastasis of <2 mm was identified. CONCLUSION: A specialist minimal access team can safely and reliably reproduce this technique for sentinel lymph node excision.

Is it possible to intraoperatively modulate the extent of thyroidectomy in small papillary thyroid carcinoma?

BACKGROUND: Thyroid lobectomy is the preferred option for small, unifocal papillary thyroid carcinoma. Involvement of the central neck lymph nodes is an indication for total thyroidectomy plus central neck dissection. We aimed to verify if frozen section examination of ipsilateral central neck nodes can identify the subgroup of patients scheduled for thyroid lobectomy intraoperatively who could benefit of more extensive initial operative treatment. METHODS: Ninety-four consenting patients with clinically unifocal cN0 papillary thyroid carcinoma underwent thyroid lobectomy plus ipsilateral central neck dissection with frozen section examination. If the frozen section examination was positive for metastases, a completion thyroidectomy and a bilateral central neck dissection were accomplished during the same procedure. RESULTS: Frozen section examination identified occult nodal metastases in 25 of the 94 patients who then underwent immediate completion thyroidectomy and bilateral central neck dissection. Overall, central neck node metastases were found at final histology in 35 cases: occult micrometastases were observed in additional 9 patients and nodal metastases ≥2 mm in additional 1 patient. CONCLUSION: Intraoperative assessment of nodal status obtained with ipsilateral central neck dissection and frozen section examination is able to change the extent of thyroidectomy in about one-fourth of patients scheduled for thyroid lobectomy. Frozen section examination appears a safe and effective strategy to decrease the need of a second-step completion procedure and, theoretically, the risk of recurrence.

Can risk groups accurately predict non-sentinel lymph node metastasis in sentinel lymph node-positive endometrial cancer patients? A Turkish Gynecologic Oncology Group Study (TRSGO-SLN-004).

BACKGROUND AND OBJECTIVES: The purpose of this study was to find out the risk factors associated with non-sentinel lymph node metastasis and determine the incidence of non-sentinel lymph node metastasis according to risk groups in sentinel lymph node (SLN)-positive endometrial cancer patients. METHODS: Patients who underwent at least bilateral pelvic lymphadenectomy after SLN mapping were retrospectively analyzed. Patients were categorized into low, intermediate, high-intermediate, and high-risk groups defined by ESMO-ESGO-ESTRO. RESULTS: Out of 395 eligible patients, 42 patients had SLN metastasis and 16 (38.1%) of them also had non-SLN metastasis. Size of SLN metastasis was the only factor associated with non-SLN metastasis (p = .012) as 13/22 patients with macrometastasis, 2/10 with micrometastasis and 1/10 with isolated tumor cells (ITCs) had non-SLN metastasis. Although all 4 metastases (1.8%) among the low-risk group were limited to SLNs, the non-SLN involvement rate in the high-risk group was 42.9% and all of these were seen in patients with macrometastatic SLNs. CONCLUSIONS: Non-SLN metastasis was more frequent in higher-risk groups and the risk of non-SLN metastasis increased with the size of SLN metastasis. Proceeding to complete lymphadenectomy when SLN is metastatic should further be studied as the effect of leaving metastatic non-SLNs in-situ is not known.

The impact of low-volume metastasis on disease-free survival of women with early-stage cervical cancer.

PURPOSE: We aimed to assess the impact of low-volume metastasis (micrometastasis and isolated tumor cells) on disease-free survival (DFS) of women with early-stage cervical cancer. METHODS: Women with clinically suspected stage 1A-IB2 (FIGO 2018 classification) disease who underwent retroperitoneal nodal staging between October 2010 and April 2018, were retrospectively analyzed. The group of women who had undergone lymphadenectomy and standard node pathologic analysis (H&E group), were compared to the group undergoing sentinel node mapping (SLN) and ultrastaging with or without lymphadenectomy (ultrastaging group). At a median follow-up of 45 months, the DFS curves were analyzed. RESULTS: Overall, 573 patients were revised (272 in the H&E group and 302 in the ultrastaging group). Eighty-five patients presented lymph node metastasis (32 in H&E, 53 in ultrastaging). Ultrastaging protocol increased the rate of low-volume metastasis by 5.6%. Twenty patients showed exclusive micrometastasis or ITC's. Seventy-three recurrences occurred (35 in H&E, 38 in ultrastaging). Only 1 out of 53 patients in the ultrastaging group (1.9%) presented with micrometastasis recurred. The 3-year disease-free survival was 89% for the H&E group, and 88% for the ultrastaging group, respectively (p = 0.175). CONCLUSION: Ultrastaging analysis allowed increasing the detection of low volume metastasis in women with early-stage cervical cancer. However, the type of nodal staging did not have an impact on patients' 3-year disease-free survival.

Disparities of Management of the Axilla in Women With Clinically Node Negative Breast Cancer.

BACKGROUND: In women with clinically node-negative breast cancer, sentinel lymph node biopsy is the first step in axillary staging. A randomized trial published in 2013 concluded that patients with sentinel lymph node micrometastases (N1mi) do not benefit from axillary lymph node dissection (ALND). We hypothesized that disparities exist in management of the axilla in node-negative patients. METHODS: We included women aged >40 years with nonmetastatic, clinically node-negative breast cancer from 2014 to 2016 in the National Cancer Database. Women treated neoadjuvantly, with large tumors (cT4), or no tumor (cT0) were excluded. Multivariable logistic regression identified patient and facility characteristics associated with undergoing ALND as first axillary surgery and completion ALND in the setting of N1mi disease. RESULTS: Of 273,951 patients, 22,898 (8%) underwent ALND first. These patients were more likely to be Hispanic (OR: 1.21, 95% CI: 1.10, 1.32), have Medicare (OR: 1.13, 95% CI: 1.03, 1.24), be uninsured (OR: 1.28, 95% CI: 1.08, 1.53), have lower educational attainment (OR: 1.24, 95% CI: 1.17, 1.32), be treated at a community hospital (OR: 1.62, 95% CI: 1.52, 1.74), or reside in the South (OR: 1.19, 95% CI: 1.12, 1.26). In the sentinel lymph node biopsy first group, 8,882 (4%) were classified as N1mi and 1,872 (21%) underwent subsequent ALND. These patients were more likely to be Hispanic (OR: 1.70, 95% CI: 1.19, 2.42) and have the lowest income (OR: 1.62, 95% CI: 1.15, 2.27). CONCLUSION: Disparities persist in implementation of evidence-based management of the axilla in women with clinically node-negative breast cancer.

Relationship between circulating lung-specific X protein messenger ribonucleic acid expression and micrometastasis and prognosis in patients with early-stage nonsmall cell lung cancer.

AIMS: To investigate the diagnostic value of lung-specific X protein (LUNX) messenger ribonucleic acid (mRNA) expression in peripheral blood of patients with nonsmall cell lung cancer (NSCLC) in micrometastasis. MATERIALS AND METHODS: Peripheral blood samples of 112 patients with NSCLC were collected, and the expression of LUNX, cytokeratin 19 (CK19), and carcinoembryonic antigen (CEA) mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The expression of LUNX, CK19, and CEA mRNA was increased in peripheral blood of patients with NSCLC compared with that of patients with benign lung disease (P < 0.05), and the sensitivity of LUNX mRNA was higher than that of CK19 and CEA mRNA (P < 0.05). LUNX-positive expression was also associated with lymph node metastasis, tumor-node-metastasis (TNM) staging, and reduced 5-year survival rate of patients in our cohort (P < 0.05). Further, the 5-year survival improved for those LUNX-positive patients who became LUNX negative following adjuvant chemotherapy compared to those who remain LUNX positive (P < 0.05). Multivariate analysis showed that lymph node metastasis, TNM stage, and LUNX mRNA expression in peripheral blood were independent prognostic factors. CONCLUSION: The detection of LUNX expression in peripheral blood of patients with NSCLC by RT-PCR is a highly specific and sensitive detection method for tumor micrometastasis that may be used for molecular diagnosis of tumor micrometastasis. LUNX mRNA expression in peripheral blood is an independent factor affecting prognosis of NSCLC and thus may reliably predict NSCLC prognosis and guide appropriate adjuvant chemotherapy treatment.

Detection of Lung Cancer Lymph Node Metastases from Whole-Slide Histopathologic Images Using a Two-Step Deep Learning Approach.

The application of deep learning for the detection of lymph node metastases on histologic slides has attracted worldwide attention due to its potentially important role in patient treatment and prognosis. Despite this attention, false-positive predictions remain problematic, particularly in the case of reactive lymphoid follicles. In this study, a novel two-step deep learning algorithm was developed to address the issue of false-positive prediction while maintaining accurate cancer detection. Three-hundred and forty-nine whole-slide lung cancer lymph node images, including 233 slides for algorithm training, 10 slides for validation, and 106 slides for evaluation, were collected. In the first step, a deep learning algorithm was used to eliminate frequently misclassified noncancerous regions (lymphoid follicles). In the second step, a deep learning classifier was developed to detect cancer cells. Using this two-step approach, errors were reduced by 36.4% on average and up to 89% in slides with reactive lymphoid follicles. Furthermore, 100% sensitivity was reached in cases of macrometastases, micrometastases, and isolated tumor cells. To reduce the small number of remaining false positives, a receiver-operating characteristic curve was created using foci size thresholds of 0.6 mm and 0.7 mm, achieving sensitivity and specificity of 79.6% and 96.5%, and 75.5% and 98.2%, respectively. A two-step approach can be used to detect lung cancer metastases in lymph node tissue effectively and with few false positives.

Prospective clinical trial of robotic sentinel lymph node assessment with isosulfane blue (ISB) and indocyanine green (ICG) in endometrial cancer and the impact of ultrastaging (NCT01818739).

OBJECTIVES: To assess the performance sentinel lymph node (SLN) biopsy and effect of ultrastaging in clinically early stage endometrial cancer. METHODS: Patients with endometrial cancer prospectively enrolled after informed consent was obtained. The cervix was injected superficially with 1 mL of ISB and 1 mL of ICG (diluted 1:25) at 3 and 9 o'clock each. SLN biopsy was followed by complete pelvic lymphadenectomy (aortic lymphadenectomy at the discretion of the surgeon). Lymph nodes (LNs) were analyzed by standard sectioning with H&E; ultrastaging of SLN was done retrospectively and blinded to treating physicians. RESULTS: 204 patients received dye injections. In 184 (90.2%) patients at least one SLN was identified. Of all patients, 138 (68%) had bilateral mapping. In the patients with successful mapping of a hemipelvis, ICG detected SLNs in 83% and ISB in 64% of cases (p < 0.0001). Median BMI (kg/m2) for patients with successful mapping was 35.7 compared to 40.1 for those who did not map (p = 0.01). Twenty-three (11.3%) patients had positive LNs. Applying the SLN algorithm, positive nodes were detected in 21/23 (91.3%). The negative predictive value (NPV) was 98.9% (95% CI: 96.01% to 99.71%). Eleven patients had positive SLN with isolated tumor cells (ITCs) or micrometastases detected on ultrastaging. Including these patients, 34 (17%) had positive LNs, increasing the NPV to 99% and sensitivity to 94%. There were no recurrences in patients with ITCs only. CONCLUSIONS: SLN assessment in endometrial cancer is feasible and safe with high NPV (99%). ICG was more effective in detecting SLN compared to ISB. Although ultrastaging detected additional positive LNs, treatment based on standard sectioning appears reasonable but further research is needed.