Audit of Targeted Sentinel Node Biopsy (TSNB) in Patients With Limited Nodal Disease Undergoing Primary Surgery

NCT07085442 | Recruiting

• 1 other identifier: PID 46
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 12

Brief Summary

Axillary ultrasound scan (AUS) is routinely employed in the UK for preoperative axillary staging and can diagnose approximately 50 - 80% of node positive patients when combined with percutaneous needle biopsy techniques (either core-biopsy or fine-needle aspiration cytology). It is recognised that nodal burden is generally higher in clinically node negative patients with abnormal nodes on AUS and confirmed on needle-biopsy to be histologically positive than patients diagnosed as node positive on sentinel node biopsy (SNB). However, up to 40% of biopsy-proven node positive patients are found to have fewer than 3 involved nodes on subsequent axillary lymph node dissection (ALND) and are potential candidates for less extensive axillary surgery with axillary radiotherapy (ART) rather than ALND. The total number of abnormal nodes on ultrasound is a key predictor of overall nodal tumour burden. The AMAROS and OTOASOR trials randomised patients with up to 2 positive sentinel nodes to either ALND or ART. These trials were conducted around the turn of the millennium and before routine use of AUS and therefore would have included a significant number of patients who were radiologically node positive (cN1). Likewise, the ACOSOG Z0011 trial that randomised a similar group of patients to either ALND or observation only, did not incorporate routine AUS and would have included some (radiological) cN1 patients. These trials revealed no adverse impact on disease-free or overall survival from omission of completion ALND. Targeted axillary dissection (TAD) was introduced a few years ago to reduce the false negative rate of SNB following neoadjuvant chemotherapy (NACT) and has been standardised as part of the ongoing ATNEC trial \[ClinicalTrials.govNCT04109079\]. This technique for axillary staging after NACT is increasingly being adopted in the UK and elsewhere. TAD is technically more straightforward and less challenging in patients undergoing primary surgery with no concerns about clip migration consequent to nodal shrinkage as part of treatment response to NACT. Furthermore, the risk of under-treating the axilla is offset by the protocol: if no disease is identified in the targeted nodes (false-negative case), then patients proceed to ALND, thereby ensuring adequate treatment. Unlike TAD following NACT, the presence of viable tumour within the sampled nodes is mandatory and finding fibrosis is irrelevant except as a response to nodal biopsy per se. Current ASCO guidelines support both SNB and TAD as staging options for patients with ultrasound-detected, biopsy-confirmed nodal disease. The Edinburgh randomised trials comparing four-node sampling with ALND demonstrated significantly lower arm morbidity with node sampling, supporting TAD as a clinically appropriate alternative in this patient population. The UK-ANZ POSNOC trial randomised 1,900 patients with \<3 macrometastases to either no further axillary treatment or additional axillary treatment. The study included cN1 patients with biopsy-confirmed nodal metastases who underwent sentinel node biopsy or TAD. Patients with \<3 macrometastases on final histology were randomised to receive no further axillary treatment or proceed with additional axillary treatment (ALND or ART). POSNOC trial will answer whether further axillary treatment provides any benefit in patients with low volume nodal disease on SNB or TAD. Notably, patients with biopsy-confirmed metastases and \<3 macrometastases on SNB/TAD are biologically and clinically similar to patients with normal AUS who are later found to have low-volume disease on SNB. Clinical decision-making and patient outcomes are driven by tumour biology and overall disease burden rather than the method of nodal disease detection. Furthermore, AUS sensitivity is operator dependent and whether FNA or core biopsy was used to sample the node. A patient considered node negative on AUS by one radiologist may be diagnosed with core biopsy confirmed nodal metastases with another radiologist. Pending the results of POSNOC trial, patients with less than 3 macrometastases are generally advised further axillary treatment, and ART is preferred over ALND to reduce the risk of lymphoedema. NodeSMART is a prospective audit collecting data on patients undergoing TAD in the primary surgery setting. Its goal is to audit surgical outcomes and benchmark them against - a) Comparing technical outcomes with those from sentinel node biopsy in the primary surgery setting and TAD performed after neoadjuvant chemotherapy. b) Assessing rates of arm lymphoedema and disease progression relative to findings from the AMAROS and Z11 trials, and the POSNOC trial once results are available. The term "Targeted Axillary Dissection" is somewhat misleading in this context, as the marked (biopsied) node is removed alongside sentinel nodes - not in isolation. NodeSMART therefore refers to the procedure more accurately as Targeted Sentinel Node Biopsy (TSNB).

Conditions

Breast Cancer; Axillary Metastases; Sentinel Lymph Node Biopsy (SLNB); Axillary Lymph Nodes Dissection; Node Positive Breast Cancer; Axilla; Breast; Axillary Ultrasound

Keywords

Targeted Axillary Dissection; Targeted Sentinel Node Biopsy; NodeSMART; Breast Cancer; Sentinel Node Biopsy; Axillary Lymph Nodes Dissection; Axillary Node Clearance

Outcome Measures

Primary Outcomes (20)

• Patients with ≤2 nodal macrometastases identified on histology.

  To determine the number of patients with fewer than 3 nodal macrometastases on final histology, and assess whether ultrasound-detected abnormal nodes and tumour characteristics can predict axillary nodal burden.

  12 months

• Patients with ≤2 nodal macrometastases identified on histology.

  To determine the number of patients with fewer than 3 nodal macrometastases on final histology, and assess whether ultrasound-detected abnormal nodes and tumour characteristics can predict axillary nodal burden.

  24 months

• Patients with ≤2 nodal macrometastases identified on histology.

  To determine the number of patients with fewer than 3 nodal macrometastases on final histology, and assess whether ultrasound-detected abnormal nodes and tumour characteristics can predict axillary nodal burden.

  36 months

• Patients with ≤2 nodal macrometastases identified on histology.

  To determine the number of patients with fewer than 3 nodal macrometastases on final histology, and assess whether ultrasound-detected abnormal nodes and tumour characteristics can predict axillary nodal burden.

  48 months

• Patients with ≤2 nodal macrometastases identified on histology.

  To determine the number of patients with fewer than 3 nodal macrometastases on final histology, and assess whether ultrasound-detected abnormal nodes and tumour characteristics can predict axillary nodal burden.

  60 months

• Identification rate of marked node

  Identification rate of marked biopsied node at axillary surgery

  12 months

• Identification rate of marked node

  Identification rate of marked biopsied node at axillary surgery

  24 months

• Identification rate of marked node

  Identification rate of marked biopsied node at axillary surgery

  36 months

• Identification rate of marked node

  Identification rate of marked biopsied node at axillary surgery

  48 months

• Identification rate of marked node

  Identification rate of marked biopsied node at axillary surgery

  60 months

• False negative rate of targeted sentinel node biopsy

  False negative rate of targeted sentinel node biopsy (FN/TP+FN)

  12 months

• False negative rate of targeted sentinel node biopsy

  False negative rate of targeted sentinel node biopsy (FN/TP+FN)

  24 months

• False negative rate of targeted sentinel node biopsy

  False negative rate of targeted sentinel node biopsy (FN/TP+FN)

  36 months

• False negative rate of targeted sentinel node biopsy

  False negative rate of targeted sentinel node biopsy (FN/TP+FN)

  48 months

• False negative rate of targeted sentinel node biopsy

  False negative rate of targeted sentinel node biopsy (FN/TP+FN)

  60 months

• Arm lymphoedema

  Arm lymphoedema self reported by the patient or identified during routine care, resulting in referral to a lymphoedema clinic.

  12 months

• Arm lymphoedema

  Arm lymphoedema self reported by the patient or identified during routine care, resulting in referral to a lymphoedema clinic.

  24 months

• Arm lymphoedema

  Arm lymphoedema self reported by the patient or identified during routine care, resulting in referral to a lymphoedema clinic.

  36 months

• Arm lymphoedema

  Arm lymphoedema self reported by the patient or identified during routine care, resulting in referral to a lymphoedema clinic.

  48 months

• Arm lymphoedema

  Arm lymphoedema self reported by the patient or identified during routine care, resulting in referral to a lymphoedema clinic.

  60 months

Secondary Outcomes (25)

• Axillary recurrence

  12 months

• Axillary recurrence

  24 months

• Axillary recurrence

  36 months

• Axillary recurrence

  48 months

• Axillary recurrence

  60 months

Study Arms (1)

Patients with biopsy proven nodal metastases (cN1) and not receiving neoadjuvant chemotherapy

Patients with T1 or T2 tumours with biopsy proven nodal metastases (cN1) and with ≤2 abnormal nodes on axillary ultrasound

Procedure: Targeted Sentinel Node Biopsy (TSNB)

Interventions

Targeted Sentinel Node Biopsy (TSNB) PROCEDURE

Targeted Sentinel Node Biopsy will be performed according to routine local practice. The procedure has been standardised for the post-NACT setting as part of the ongoing ATNEC trial. Sites are advised to follow the ATNEC protocol in the primary surgery setting, using either a dual- or single-tracer sentinel node biopsy technique, with localisation and removal of the marked biopsy proven positive node, and removal of at least 3 nodes.

Patients with biopsy proven nodal metastases (cN1) and not receiving neoadjuvant chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

cT1-2N1M0 breast cancer patients aged 18 years or older, with needle biopsy proven nodal metastases, ≤2 abnormal nodes on imaging, and are undergoing sentinel node biopsy and removal of the marked involved node.

You may qualify if:

• cT1-2N1M0 breast cancer
• FNA or core biopsy confirmed axillary nodal metastases
• ≤2 abnormal nodes on imaging
• Undergo a dual tracer or single tracer sentinel node biopsy along with removal of the marked node (Targeted Sentinel Node Biopsy, TSNB)
• or 2 macrometastases identified in the removed nodes, with at least three nodes removed
• If the sentinel node(s) cannot be localised on SNB: axillary node sampling should be performed, the patient will be eligible if 1 or 2 macrometastases are identified in the removed nodes, with at least three nodes removed.
• If the node is not marked or the marked node is not removed, the patient will be eligible if 1 or 2 macrometastases are identified in the removed nodes, with at least three nodes removed.

You may not qualify if:

• Neoadjuvant chemotherapy
• Previous ipsilateral axillary nodal surgery
• cT3-4 breast cancer
• ≥3 abnormal nodes on imaging

Sponsors & Collaborators

• University Hospitals of Derby and Burton NHS Foundation Trust: lead

Study Sites (12)

Burnley General Teaching Hospital

Burnley, United Kingdom

RECRUITING

Addenbrooke's Hospital

Cambridge, United Kingdom

RECRUITING

University Hospitals of Derby and Burton

Derby, United Kingdom

RECRUITING

Gartnavel General Hospital

Glasgow, United Kingdom

RECRUITING

Wycombe Hospital

High Wycombe, HP11 2TT, United Kingdom

RECRUITING

Liverpool University Hospitals NHS Foundation Trust

Liverpool, United Kingdom

RECRUITING

Royal Alexandra Hospital

Paisley, United Kingdom

RECRUITING

The Shrewsbury and Telford Hospital NHS Trust

Shrewsbury, United Kingdom

RECRUITING

Mersey and West Lancashire Teaching Hospitals

St Helens, United Kingdom

RECRUITING

University Hospital of North Tees and Hartlepool

Stockton-on-Tees, United Kingdom

RECRUITING

Warrington and Halton Teaching Hospitals

Warrington, United Kingdom

RECRUITING

The Royal Wolverhampton NHS Trust

Wolverhampton, WV10 0QP, United Kingdom

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Amit Goyal

  University Hospitals of Derby and Burton NHS Foundation Trust

  STUDY CHAIR

Central Study Contacts

Amit Goyal

CONTACT

01332 786958; amit.goyal@nhs.net

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: July 25, 2025
• Study Start: January 17, 2025
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 1, 2032
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (12)