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

Abstract

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

De-escalation of axillary treatment in the event of a positive sentinel lymph node biopsy in cT1–2 N0 breast cancer treated with mastectomy: nationwide registry study (BOOG 2013-07)

“…Currently, patients undergoing mastectomy are still being enrolled in the study to increase its power. In the POSNOC trial 34 , 1900 patients with cT1–2 N0 breast cancer and 1 or 2 macrometastatic SLNs are being randomized between adjuvant systemic therapy and adjuvant systemic therapy with either ALND or axillary RT, with 5-year axillary recurrence rate as the primary endpoint. The first results are expected in 2026.…”

Risk factors of non-sentinel lymph node metastasis in breast cancer with 1–2 sentinel lymph node macrometastases underwent total mastectomy: a case-control study

“…The primary endpoint is axillary recurrence at 5 years. As of June 2021, POSNOC study had completed 1866 cases [ 25 ]. The results of the ACOSOG Z0011 and IBCSG 23-01 studies have changed the previous breast cancer treatment strategy.…”

Refining prognostication in early breast cancer

“…PhH3 is a proliferation marker that is specific for mitosis, as it is expressed from the late G 2 phase to M transition, and rapidly degrades on entry into the G 1 phase [37]. Therefore, PhH3 labelling has been reported to closely correlate with mitotic figure detection on standard haematoxylin and eosin (H&E)stained sections [38,39]. As compared with the MAI, PhH3 is relatively easy to assess, as its bright staining offers easy visualisation of mitotic figures by morphology, resulting in a high accuracy of detection.…”

“…Consequently, small metastatic deposits such as micro-metastases and isolated tumor cells were observed more frequently [35][36][37]. Then, the Z0011 and AMAROS trials revealed that completion ALND (cALND) may be omitted in clinically node negative patients with one or two metastatic sentinel lymph nodes (SLNs) [38,39], and as a consequence information about the overall number of involved lymph nodes is no longer routine practice. This loss of detail on the extent of nodal involvement does not compromise outcome [38,39], but may affect the clinical decision-making process and certainly comes with a sense of uncertainty for many clinicians.…”

“…These studies showed that a substantial risk (30%) of residual positive lymph does not impair survival nor locoregional control in patients receiving adjuvant radiotherapy or systemic therapy. The aforementioned trials merely included patients undergoing breast conserving surgery and results of randomized trials comparing ALND to axillary radiotherapy or observation in SLNB positive patients treated by mastectomy remain to be awaited [38][39][40]. While oncological safety is warranted in the context of ever less invasive axillary surgery, from a staging perspective, clinicians struggle with the increasing lack of information about the extent of lymph node involvement.…”