POSNOC—POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy: a randomised controlled trial of axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes

IntroductionACOSOG-Z0011(Z11) trial showed that axillary node clearance (ANC) may be omitted in women with ≤2 positive nodes undergoing breast conserving surgery (BCS) and whole breast radiotherapy (RT). A confirmatory study is needed to clarify the role of axillary treatment in women with ≤2 macrometastases undergoing BCS and groups that were not included in Z11 for example, mastectomy and those with microscopic extranodal invasion. The primary objective of POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy (POSNOC) is to evaluate whether for women with breast cancer and 1 or 2 macrometastases, adjuvant therapy alone is non-inferior to adjuvant therapy plus axillary treatment, in terms of 5-year axillary recurrence.Methods and analysisPOSNOC is a pragmatic, multicentre, non-inferiority, international trial with participants randomised in a 1:1 ratio. Women are eligible if they have T1/T2, unifocal or multifocal invasive breast cancer, and 1 or 2 macrometastases at sentinel node biopsy, with or without extranodal extension. In the intervention group women receive adjuvant therapy alone, in the standard care group they receive ANC or axillary RT. In both groups women receive adjuvant therapy, according to local guidelines. This includes systemic therapy and, if indicated, RT to breast or chest wall. The UK Radiotherapy Trials Quality Assurance Group manages the in-built radiotherapy quality assurance programme. Primary endpoint is 5-year axillary recurrence. Secondary outcomes are arm morbidity assessed by Lymphoedema and Breast Cancer Questionnaire and QuickDASH questionnaires; quality of life and anxiety as assessed with FACT B+4 and State/Trait Anxiety Inventory questionnaires, respectively; other oncological outcomes; economic evaluation using EQ-5D-5L. Target sample size is 1900. Primary analysis is per protocol. Recruitment started on 1 August 2014 and as of 9 June 2021, 1866 participants have been randomised.Ethics and disseminationProtocol was approved by the National Research Ethics Service Committee East Midlands—Nottingham 2 (REC reference: 13/EM/0459). Results will be submitted for publication in peer-reviewed journals.Trial registration numberISRCTN54765244; NCT0240168Cite Now

EP.TH.166Evaluation of the impact of the COVID-19 pandemic on the practice of axillary node dissection

Aims The Association of Breast Surgery's "COVID-altered" guidance for management of breast cancer during the COVID-19 pandemic, includes that neoadjuvant chemotherapy was only to be used only in inoperable disease and not to downstage the axilla. Delayed presentation with increased nodal involvement was also a concern. We aim to establish if axillary node dissection (AND) increased in the context of pandemic. Methods Patients undergoing surgery for breast cancer were identified from theatre coding in a UK breast unit. Pre-COVID (March 2018 - February 2020) and COVID pandemic (March - September 2020) cohorts were compared. Indication, tumour receptor status, neoadjuvant chemotherapy (NAC) and deviation from routine practice were ascertained for those undergoing AND. Trust Caldicott and audit department approval was obtained for this retrospective review of practice. Results AND was performed in 20.2% (23/114) of breast cancer operations during the pandemic compared with 18.97% (78/411) pre-COVID. Indication for AND during the pandemic and pre-COVID respectively - clinically node positive 82.6%/79.4%; positive sentinel node biopsy 4.3%/17.9%; recurrence or metastases from contralateral cancer 13%/2.5%. NAC preceded AND in 30% of cases in both cohorts. NAC for one node positive HER2+ cancer was omitted due to the pandemic and another patient had adjuvant chemotherapy omitted for a HER2+ cancer with a single positive sentinel node mandating an AND which yielded no further positive nodes. Conclusions The COVID-19 pandemic has not significantly impacted rates of AND in our practice. However, we identified 2 patients who may have avoided AND with normal chemotherapy protocols.

Analysis of Axillary Management Following Mastectomy With a Positive Sentinel Lymph Node Biopsy

BACKGROUND: Axillary lymph node dissection (ALND) with or without postmastectomy radiation therapy (PMRT) was traditionally the standard of care for patients with a positive sentinel node following mastectomy. However, recent clinical trial data has led to an interest in de-escalating therapy and a debate over optimal axillary management. We sought to assess current practice patterns and the impact of different approaches to managing positive sentinel nodes following mastectomy. METHODS: Using the National Cancer Database (NCDB), patients with clinical T1-2 N0 M0 breast cancer from 2012-2015 treated with a mastectomy who were found to have a single positive sentinel node were analyzed. A logistic regression model stratified by patients’ characteristics in association to the type of axillary treatment received was performed.RESULTS: We identified 12,137 women with a positive sentinel lymph node biopsy (SLNB) at the time of mastectomy. Of these, 4,221 had an ALND; 1,609 received PMRT; 1,565 underwent combination therapy, and 4,742 had no further treatment following SLNB (NFT). Factors associated with an increased likelihood of further axillary treatment included younger age (<40), Midwest location, larger primary tumor size (T2), and high grade. There was no difference in short-term overall survival among these approaches. CONCLUSION: Our study indicates significant practice variation in the axillary management of patients with metastasis limited to a single sentinel node undergoing mastectomy. The clinical variation observed raises the possibility of unnecessary or overtreatment of the axilla. These findings suggest a need to expand the adoption of evidenced-based clinical protocols to improve quality of care.

Lymphadenectomy after a positive sentinel node biopsy in patients with cutaneous melanoma. A systematic review

Complete lymph node dissection (CLND) following a positive sentinel lymph node biopsy (SLNB) has been the standard treatment for years. However, there is increasing evidence that CLND could be omitted. Approximately 80% of patients with a positive sentinel node biopsy do not have additional nodal involvement; in these contexts, the SLNB could be diagnostic and therapeutic. However, in this group of patients, the therapeutic effect of CLND is unclear.A systematic search was performed in EMBASE and MEDLINE (PubMed), for studies published between January 1, 2014 and December 31, 2019. Studies were included when they compared immediate CLND and observation after a positive sentinel node. The outcomes of interest were: Overall Survival (OS), melanoma-specific survival (MSS), and disease-free survival (DFS).Eleven studies met the inclusion criteria. Two randomized clinical trials reported no differences in OS or MSS when complete lymph dissection was compared with observation alone. An increase in regional relapse was observed in the CLND group, and in one randomized controlled trial (RCT) the rate of disease-free survival was superior in those patients.Most populations in both RCTs had low sentinel lymph node biopsy (SLNB) metastatic deposits, and head and neck melanomas were not included or underrepresented. When CNLD was omitted, an active surveillance protocol was carried out.The evidence supports that CLND in SLNB positive patients does not confer a survival benefit. Sentinel tumor burden, localization of primary tumor, and feasibility of active surveillance should be taken into account in treatment decisions.