Prognostic role of lymph node micrometastasis in oral and oropharyngeal cancer: A systematic review.

BACKGROUND: An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC. METHODS: PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact. RESULTS: Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis. CONCLUSION: The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas.

Meta-analysis on axillary lymph node metastasis rate in ductal carcinoma in situ with microinvasion.

OBJECTIVE: To address the question of axillary lymph node staging in ductal carcinoma in situ with microinvasion (DCIS-MI), we retrospectively evaluated axillary lymph nodes metastasis (ALNM) rate in a cohort of postsurgical DCIS-MI patients. By analyzing these data, we aimed to generate clinically relevant insights to inform treatment decision-making for this patient population. METHODS: A systematic search was conducted on PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang Database, Wipe, and China Biomedical Literature Database to identify relevant publications in any language. All the analyses were performed using Stata 16.0 software. RESULTS: Among the 28 studies involving 8279 patients, the pooled analysis revealed an ALNM rate of 8% (95% CI, 7% to 10%) in patients with DCIS-MI. Furthermore, the rates of axillary lymph node macrometastasis, micrometastasis, and ITC in patients with DCIS-MI were 2% (95% CI, 2% to 3%), 3% (95% CI, 2% to 4%), and 2% (95% CI, 1% to 3%), respectively. Moreover, 13 studies investigated the non-sentinel lymph node (Non-SLN) metastasis rate, encompassing a total of 1236 DCIS-MI cases. The pooled analysis identified a Non-SLN metastasis rate of 33% (95% CI, 14% to 55%) in patients with DCIS-MI. CONCLUSION: The SLNB for patients with DCIS-MI is justifiable and could provide a novel therapeutic basis for systemic treatment decisions.

Sentinel Lymph Node Mapping in Lung Cancer: A Pilot Study for the Detection of Micrometastases in Stage I Non-Small Cell Lung Cancer.

Lymphadenectomy represents a fundamental step in the staging and treatment of non-small cell lung cancer (NSCLC). To date, the extension of lymphadenectomy in early-stage NSCLC is a debated topic due to its possible complications. The detection of sentinel lymph nodes (SLNs) is a strategy that can improve the selection of patients in which a more extended lymphadenectomy is necessary. This pilot study aimed to refine lymph nodal staging in early-stage NSCLC patients who underwent robotic lung resection through the application of innovative intraoperative sentinel lymph node (SLN) identification and the pathological evaluation using one-step nucleic acid amplification (OSNA). Clinical N0 NSCLC patients planning to undergo robotic lung resection were selected. The day before surgery, all patients underwent radionuclide computed tomography (CT)-guided marking of the primary lung lesion and subsequently Single Photon Emission Computed Tomography (SPECT) to identify tracer migration and, consequently, the area with higher radioactivity. On the day of surgery, the lymph nodal radioactivity was detected intraoperatively using a gamma camera. SLN was defined as the lymph node with the highest numerical value of radioactivity. The OSNA amplification, detecting the mRNA of CK19, was used for the detection of nodal metastases in the lymph nodes, including SLN. From March to July 2021, a total of 8 patients (3 female; 5 male), with a mean age of 66 years (range 48-77), were enrolled in the study. No complications relating to the CT-guided marking or preoperative SPECT were found. An average of 5.3 lymph nodal stations were examined (range 2-8). N2 positivity was found in 3 out of 8 patients (37.5%). Consequently, pathological examination of lymph nodes with OSNA resulted in three upstages from the clinical IB stage to pathological IIIA stage. Moreover, in 1 patient (18%) with nodal upstaging, a positive node was intraoperatively identified as SLN. Comparing this protocol to the usual practice, no difference was found in terms of the operating time, conversion rate, and complication rate. Our preliminary experience suggests that sentinel lymph node detection, in association with the accurate pathological staging of cN0 patients achieved using OSNA, is safe and effective in the identification of metastasis, which is usually undetected by standard diagnostic methods.

Validation study on the 2 mm diameter cutoff in lymph node-positive cases following radical prostatectomy in accordance with the AJCC/UICC TNM 8th edition: Real-world data analysis from a Japanese cohort.

OBJECTIVES: The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition has proposed micrometastasis as a lymph node metastasis (LN+) of diameter ≤2 mm in prostate cancer. However, supporting evidence has not described. We evaluated LN+ patients' survival after radical prostatectomy (RP) based on the LN maximum tumor diameter (MTD). METHODS: Data from 561 LN+ patients after RP and pelvic LN dissection (PLND) treated between 2006 and 2019 at 33 institutions were retrospectively investigated. Patients were stratified by a LN+ MTD cutoff of 2 mm. Outcomes included castration resistance-free survival (CRFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: In total, 282 patients were divided into two groups (LN+ MTD >2 mm [n = 206] and ≤2 mm [n = 76]). Patients of LN+ status >2 mm exhibited significantly decreased CRFS and MFS, and poorer CSS and OS. No patients developed CRPC in the LN+ status ≤2 mm group when the PLND number was ≥14. Multivariate analysis showed the number of LN removed, RP Gleason pattern 5, and MTD in LN+ significantly predicted CRFS. CONCLUSIONS: Patients of LN+ status ≤2 mm showed better prognoses after RP. In all the patients in the ≤2-mm group, the progression to CRPC could be prevented with appropriate interventions, particularly when PLND is performed accurately. Our findings support the utility of the pN substaging proposed by the AJCC/UICC 8th edition; this will facilitate precision medicine for patients with advanced prostate cancer.

Incidence of sentinel lymph node metastases in apparent early-stage endometrial cancer: a multicenter observational study.

OBJECTIVE: Ultrastaging is accurate in detecting nodal metastases, but increases costs and may not be necessary in certain low-risk subgroups. In this study we examined the risk of nodal involvement detected by sentinel lymph node (SLN) biopsy in a large population of apparent early-stage endometrial cancer and stratified by histopathologic characteristics. Furthermore, we aimed to identify a subgroup in which ultrastaging may be omitted. METHODS: We retrospectively included patients who underwent SLN (with bilateral mapping and no empty nodal packets on final pathology) ± systematic lymphadenectomy for apparent early-stage endometrial cancer at two referral cancer centers. Lymph node status was determined by SLN only, regardless of non-SLN findings. The incidence of macrometastasis, micrometastasis, and isolated tumor cells (ITC) was measured in the overall population and after stratification by histotype (endometrioid vs serous), myometrial invasion (none, <50%, ≥50%), and grade (G1, G2, G3). RESULTS: Bilateral SLN mapping was accomplished in 1570 patients: 1359 endometrioid and 211 non-endometrioid, of which 117 were serous. The incidence of macrometastasis, micrometastasis, and ITC was 3.8%, 3.4%, and 4.8%, respectively. In patients with endometrioid histology (n=1359) there were 2.9% macrometastases, 3.2% micrometastases, and 5.3% ITC. No macro/micrometastases and only one ITC were found in a subset of 274 patients with low-grade (G1-G2) endometrioid endometrial cancer without myometrial invasion (all <1%). The incidence of micro/macrometastasis was higher, 2.8%, in 708 patients with low-grade endometrioid endometrial cancer invading <50% of the myometrium. In patients with serous histology (n=117), the incidence of macrometastases, micrometastasis, and ITC was 11.1%, 6.0%, and 1.7%, respectively. For serous carcinoma without myometrial invasion (n=36), two patients had micrometastases for an incidence of 5.6%. CONCLUSIONS: Ultrastaging may be safely omitted in patients with low-grade endometrioid endometrial cancer without myometrial invasion. No other subgroups with a risk of nodal metastasis of less than 1% have been identified.

Tertiary prevention strategies for micrometastatic lymph node cervical cancer: A systematic review and a prototype of an adapted model of care.

PURPOSE: We found a need for balancing the application of clinical guidelines and tailored approaches to follow-up of cervical cancer (CC) patients in the lymph node micrometastatic (MICs) setting. This review aimed to determine the current knowledge of management of MIC-positive CC cases. METHODOLOGY: We addressed prognostic and risk of recurrence monitoring impacts associated with MIC+ cases. The electronic databases for literature and relevant articles were analysed. RESULTS: Fifteen studies, (4882 patients), were included in our systematic review. While the results show that MICs significantly worsen prognosis in early CC. A tertiary prevention algorithm for low volume lymph node disease may stratify follow-up according to the burden of nodal disease and provide data that helps improve follow-up performance. CONCLUSION: MICs worsen prognosis and should be managed as suggested by the algorithm. However, this algorithm must be externally validated. The clinical impact of isolated tumor cells (ITC) remains unclear.

[Clinicopathological factors and clinical significance of No.12b lymph node metastasis in gastric antrum cancer].

Objective: To investigate the clinicopathological factors and clinical significance of (micro)metastasis in No.12b lymph node in patients with gastric antrum cancer. Methods: This was a retrospective cohort study of data of 242 patients with gastric adenocarcinoma without distant metastasis, complete follow-up data, and no preoperative anti-tumor therapy or history of other malignancies. All study patients had undergone radical gastrectomy (at least D2 radical range) + No.12b lymph node dissection in the Department of Gastric Surgery of Liaoning Cancer Hospital from January 2007 to December 2012. Immunohistochemical staining with antibody CK8/18 was used to detect micrometastasis to lymph nodes. Patients with positive findings on hematoxylin and eosin stained specimens and/or CK8/18 positivity in No.12b lymph node were diagnosed as having No.12b (micro)metastasis and included in the No.12b positive group. All other patients were classified as 12b negative. We investigated the impact of No.12b (micro)metastasis by comparing the clinicopathological characteristics and recurrence free survival (RFS) of these two groups of patients and subjecting possible risk factors to statistical analysis. Results: Traditional hematoxylin-eosin staining showed that 15/242 patients were positive for No.12b lymph nodes and 227 were negative. A total of 241 negative No. 12b lymph nodes were detected. Immunohistochemical testing revealed that seven of these 241 No.12b lymph nodes (2.9%) were positive for micrometastasis. A further seven positive nodes were identified among the 227 nodes (3.1%) that had been evaluated as negative on hematoxylin-eosin-stained sections. Thus, 22 /242 patients' (9.1%) No.12b nodes were positive for micrometastases, the remaining 220 (90.9%) being negative. Factor analysis showed that No.12b lymph node (micro) metastasis is associated with more severe invasion of the gastric serosa (HR=3.873, 95%CI: 1.676-21.643, P=0.006), T3 stage (HR=1.615, 95%CI: 1.113-1.867, P=0.045), higher N stage (HR=1.768, 95%CI: 1.187-5.654, P=0.019), phase III of TNM stage (HR=2.129, 95%CI: 1.102-3.475, P=0.046), and lymph node metastasis in the No.1/No.8a/No.12a groups (HR=0.451, 95%CI: 0.121-0.552, P=0.035; HR=0.645, 95%CI:0.071-0.886, P=0.032; HR=1.512, 95%CI: 1.381-2.100, P=0.029, respectively). Survival analysis showed that the 5-year RFS of patients in the No.12b positive group was worse than that of those in the No.12b negative group (18.2% vs. 34.5%, P<0.001). Independent predictors of RFS were poorer differentiation of the primary tumor (HR=0.528, 95%CI:0.288-0.969, P=0.039), more severe serous invasion (HR=1.262, 95%CI:1.039-1.534, P=0.019), higher T/N/TNM stage (HR=4.880, 95%CI: 1.909-12.476, P<0.001; HR=2.332, 95%CI: 1.640-3.317, P<0.001; HR=0.139, 95%CI: 0.027-0.713, P=0.018, respectively), and lymph node metastasis in the No.12a/No.12b group(HR=0.698, 95%CI:0.518-0.941, P=0.018; HR=0.341, 95%CI:0.154-0.758,P=0.008, respectively). Conclusion: Detection of micrometastasis can improve the rate of positive lymph nodes. In patients with gastric antrum cancer, dissection of group No.12b lymph nodes may improve the prognosis of those with intraoperative evidence of tumor invasion into the serosa, more than two lymph node metastases, and suspicious lymph nodes in groups No.1 / No.8a / 12a.

The role of micrometastasis in high-risk skin cancers.

The propensity to metastasize is the most important prognostic indicator for solid cancers. New insights into the mechanisms of early carcinogenesis have revealed micrometastases are generated far earlier than previously thought. Evidence supports a synergistic relationship between vascular and lymphatic seeding which can occur before there is clinical evidence of a primary tumour. Early vascular seeding prepares distal sites for colonisation while regional lymphatics are co-opted to promote facilitative cancer cell mutations. In response, the host mounts a global inflammatory and immunomodulatory response towards these cells supporting the concept that cancer is a systemic disease. Cancer staging systems should be refined to better reflect cancer cell loads in various tissue compartments while clinical perspectives should be broadened to encompass this view when approaching high-risk cancers. Measured adjunctive therapies implemented earlier for low-volume, in-transit cancer offers the prospect of preventing advanced disease and the need for heroic therapeutic interventions. This review seeks to re-appraise how we view the metastatic process for solid cancers. It will explore in-transit metastasis in the context of high-risk skin cancer and how it dictates disease progression. It will also discuss how these implications will influence our current staging systems and its consequences on management.

High-precision detection and navigation surgery of colorectal cancer micrometastases.

Surgical resection is an effective treatment for colorectal cancer (CRC) patients, whereas occult metastases hinder the curative effect. Currently, there is no effective method to achieve intraoperatively diagnosis of tumor-positive lymph nodes (LNs). Herein, we adopt a near-infrared-II (NIR-II) organic donor-pi-acceptor-pi-donor probe FE-2PEG, which exhibits bright fluorescence over 1100 nm, excellent photostability, blood circulation time, and biocompatibility, to achieve high-performance bioimaging with improved temporal and spatial resolution. Importantly, the FE-2PEG shows efficient passive enrichment in orthotopic CRC, metastatic mesenteric LNs, and peritoneal metastases by enhanced permeability and retention effect. Under NIR-II fluorescence-guided surgery (FGS), the peritoneal micrometastases were resected with a sensitivity of 94.51%, specificity of 86.59%, positive predictive value (PPV) of 96.57%, and negative predictive value of 79.78%. The PPV still achieves 96.07% even for micrometastases less than 3 mm. Pathological staining and NIR-II microscopy imaging proved that FE-2PEG could successfully delineate the boundary between the tumor and normal tissues. Dual-color NIR-II imaging strategy with FE-2PEG (1100 ~ 1300 nm) and PbS@CdS quantum dots (> 1500 nm) successfully protects both blood supply and normal tissues during surgery. The NIR-II-based FGS provides a promising prospect for precise intraoperative diagnosis and minimally invasive surgery of CRC.

Outcomes in Premenopausal Patients with HR+/HER2- Breast Cancer and Lymph Node Micrometastasis Based on the 21-Gene Recurrence Score.

BACKGROUND: Postmenopausal patients with hormone receptor positive, HER2-negative (HR+/HER2-) early breast cancer (EBC) and 21-gene OncotypeDX (ODX) recurrence scores (RS) <26 do not benefit from chemoendocrine therapy ("CET") compared to endocrine monotherapy ("E"), regardless of nodal status. In premenopausal patients, nodal status is significant in interpretation of RS. However, guidelines are not explicit in recommendations for patients with micrometastasis ("pN1mi" staging). METHODS: A cohort of patients aged <50 years with HR+/HER2- EBC who underwent ODX testing was identified within the National Cancer Database 2004-2019 dataset. We confirmed the prognostic value of ODX in pN1mi disease with multivariate Cox regression for overall survival (OS). We explored how patterns of practice differed by nodal status in cases of low RS (<26) with chi-squared testing. Finally, we performed Kaplan-Meier models comparing OS for those with RS <26 receiving E versus CET, controlling for nodal status. RESULTS: Of 72 068 patients aged <50 years with HR+/HER2- EBC, 6.1% (n = 4402) had micrometastasis. Multivariate Cox regression confirmed prognostic value of ODX in this pN1mi cohort (P < .001). In the context of RS <26, CET was used most commonly in patients with 1-3 involved lymph nodes ("pN1a-c" disease), less frequently in pN1mi disease, and least in node-negative ("pN0") disease. A benefit in OS was observed in cases with RS <26 and pN1a-c receiving CET vs. E (P = .017), but not in pN1mi (P = .49) or pN0 (P = .57) disease. CONCLUSION: Our large registry analysis found CET was associated with improved OS in pN1a-c, but not in pN1mi or pN0 disease.

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease. PATIENTS AND METHODS: A total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics. RESULTS: A total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III-IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC. CONCLUSIONS: In our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC.

MILACC study: could undetected lymph node micrometastases have impacted recurrence rate in the LACC trial?

OBJECTIVE: The etiology of inferior oncologic outcomes associated with minimally invasive surgery for early-stage cervical cancer remains unknown. Manipulation of lymph nodes with previously unrecognized low-volume disease might explain this finding. We re-analyzed lymph nodes by pathologic ultrastaging in node-negative patients who recurred in the LACC (Laparoscopic Approach to Cervical Cancer) trial. METHODS: Included patients were drawn from the LACC trial database, had negative lymph nodes on routine pathologic evaluation, and recurred to the abdomen and/or pelvis. Patients without recurrence or without available lymph node tissue were excluded. Paraffin tissue blocks and slides from all lymph nodes removed by lymphadenectomy were re-analyzed per standard ultrastaging protocol aimed at the detection of micrometastases (>0.2 mm and ≤2 mm) and isolated tumor cells (clusters up to 0.2 mm or <200 cells). RESULTS: The study included 20 patients with median age of 42 (range 30-68) years. Most patients were randomized to minimally invasive surgery (90%), had squamous cell carcinoma (65%), FIGO 2009 stage 1B1 (95%), grade 2 (60%) disease, had no adjuvant treatment (75%), and had a single site of recurrence (55%), most commonly at the vaginal cuff (45%). Only one patient had pelvic sidewall recurrence in the absence of other disease sites. The median number of lymph nodes analyzed per patient was 18.5 (range 4-32) for a total of 412 lymph nodes. A total of 621 series and 1242 slides were reviewed centrally by the ultrastaging protocol. No metastatic disease of any size was found in any lymph node. CONCLUSIONS: There were no lymph node low-volume metastases among patients with initially negative lymph nodes who recurred in the LACC trial. Therefore, it is unlikely that manipulation of lymph nodes containing clinically undetected metastases is the underlying cause of the higher local recurrence risk in the minimally invasive arm of the LACC trial.

Development of a Rare Earth Nanoprobe Enables In Vivo Real-Time Detection of Sentinel Lymph Node Metastasis of Breast Cancer Using NIR-IIb Imaging.

Sentinel lymph node (SLN) biopsy plays a critical role in axillary staging of breast cancer. However, traditional SLN mapping does not accurately discern the presence or absence of metastatic disease. Detection of SLN metastasis largely hinges on examination of frozen sections or paraffin-embedded tissues post-SLN biopsy. To improve detection of SLN metastasis, we developed a second near-infrared (NIR-II) in vivo fluorescence imaging system, pairing erbium-based rare-earth nanoparticles (ErNP) with bright down-conversion fluorescence at 1,556 nm. To visualize SLNs bearing breast cancer, ErNPs were modified by balixafortide (ErNPs@POL6326), a peptide antagonist of the chemokine receptor CXCR4. The ErNPs@POL6326 probes readily drained into SLNs when delivered subcutaneously, entering metastatic breast tumor cells specifically via CXCR4-mediated endocytosis. NIR fluorescence signals increased significantly in tumor-positive versus tumor-negative SLNs, enabling accurate determination of SLN breast cancer metastasis. In a syngeneic mouse mammary tumor model and a human breast cancer xenograft model, sensitivity for SLN metastasis detection was 92.86% and 93.33%, respectively, and specificity was 96.15% and 96.08%, respectively. Of note, the probes accurately detected both macrometastases and micrometastases in SLNs. These results overall underscore the potential of ErNPs@POL6326 for real-time visualization of SLNs and in vivo screening for SLN metastasis. SIGNIFICANCE: NIR-IIb imaging of a rare-earth nanoprobe that is specifically taken up by breast cancer cells can accurately detect breast cancer macrometastases and micrometastases in sentinel lymph nodes.

Impact of analysis of the sentinel lymph node by one-step nucleic acid amplification (OSNA) compared to conventional histopathology on axillary and systemic treatment: data from the Dutch nationwide cohort of breast cancer patients.

PURPOSE: The outcome of the sentinel lymph node in breast cancer patients affects adjuvant treatment. Compared to conventional histopathology, analysis by one-step nucleic acid amplification (OSNA) harvests more micrometastasis, potentially inducing overtreatment. In this study we investigated the impact of OSNA analysis on adjuvant treatment, compared to histopathological analysis. METHODS: Data from T1-3 breast cancer patients with sentinel nodes analysed between January 2016 and December 2019 by OSNA (OSNA group, n = 1086) from Zuyderland Medical Centre, the Netherlands, were compared to concurrent data from the Netherlands Cancer Registry (NKR) where sentinel nodes were examined by histology (histology group, n = 35,143). Primary outcomes were micro- or macrometastasis, axillary treatments (axillary lymph node dissection (ALND) or axillary radiotherapy (ART)), chemotherapy, and endocrine therapy. Statistics with Pearson Chi-square. RESULTS: In the OSNA group more micrometastasis (14.9%) were detected compared to the histology group (7.9%, p < 0.001). No difference in axillary treatment between groups was detected (14.3 vs. 14.4%). In case of mastectomy and macrometastasis, ALND was preferred over ART in the OSNA group (14.9%) compared to the histology group (4.4%, p < 0.001). In cases of micrometastasis, no difference was seen. There was no difference in administration of adjuvant chemotherapy between groups. Endocrine treatment was administrated less often in the OSNA group compared to the histology group (45.8% vs. 50.8%, p < 0.002). CONCLUSION: More micrometastasis were detected by OSNA compared to histopathology, but no subsequent increase in adjuvant axillary and systematic treatment was noticed. When performing mastectomy and OSNA, there was a preference for ALND compared to ART.

Micrometastases in the sentinel node after neoadjuvant therapy. Is axillary dissection still required?

The present review intends to discuss the controversies and strengths in clinically node-positive patients with axillary nodal status ypN i+ / mi after neoadjuvant chemotherapy. Over the past 20 years, a de-escalation approach toward axillary surgery has been observed in patients with breast cancer. The worldwide use of sentinel node biopsy in the upfront setting and after primary systemic therapy substantially reduced surgical complications or late sequelae and eventually improving quality of life of patients. However, the role of axillary dissection is still unclear in patients with low residual disease post-chemotherapy, namely those with micrometastases in the sentinel node, and its prognostic role is still not very clear. The aim of the present narrative review is to report the available evidence on this topic, discussing the pros and cons of performing axillary lymph node dissection in the infrequent finding of micrometastases in the sentinel node after neoadjuvant chemotherapy. We will also describe the ongoing prospective studies which are expected to shed light and guide future decisions.

Survival impact of immediate complete lymph node dissection for Chinese acral and cutaneous melanoma with micrometastasis in sentinel nodes: a retrospective study.

Sentinel node biopsy (SNB) has become a critical part of standard surgical treatment for melanoma with no clinical metastatic evidence. However, for patients with a positive sentinel node, the MSLT-II and DeCOG-SLT trials have shown that immediate complete lymph node dissection (CLND) does not bring further survival benefits. There is still an argument among the Chinese population dominated by acral subtypes on whether CLND can be omitted. Thus, this study aims to investigate the impact of immediate CLND on relapse-free survival (RFS) in Chinese melanoma patients with a positive sentinel node. Patients with acral or cutaneous melanoma of clinical Stages I-II who received SNB procedure and were detected with nodal micrometastasis were retrospectively collected at Fudan University Cancer Center (FUSCC) from January 2017 to December 2021. The clinicopathologic features and prognostic factors for RFS were analyzed. Out of 381 patients who received SNB in the past 5 years, 130 (34%) cases with SN micrometastasis detected were included in this study. Ninety-nine patients underwent immediate CLND while the other 31 patients received observation alone. Among patients who received CLND, the non-SN(NSN)-positive rate was 22.2%. Most of the clinicopathologic factors were balanced well between the CLND and non-CLND groups. However, more patients in the CLND group were detected with BRAF and NRAS mutation (P = 0.006) and received adjuvant PD-1 monotherapy (P = 0.042) as well. There were slightly fewer N1 patients in the CLND group, although the difference did not reach statistical significance (P = 0.075). The study found no significant difference in RFS between the two groups (P = 0.184). Even for patients with the acral subtype (P = 0.925), primary T4 lesion (P = 0.769), or presence of ulceration (P = 0.249), immediate CLND did not bring more survival benefits. Immediate CLND did not bring further RFS benefit for Chinese melanoma patients with SN micrometastasis in real-world clinical practice, even for patients with acral subtype or more tumor burden such as thick Breslow invasion and ulceration.