No Axillary sUrgical Treatment In Clinically Lymph Node Negative Patients After UltraSonography

Seoul National University

Status: Active, not recruiting

Conditions: Sentinel Lymph Node; Breast Cancer

Treatments: Procedure: SLNB; Procedure: No SLNB

Study type: Interventional

Funder types: Other

Identifiers

NCT04303715

NAUTILUS study

Details and patient eligibility

About

NAUTILUS study is a prospective, multicenter, RCT. Clinically T1,T2, node negative BCS candidates with no evidence of metastases in AUS are 1:1 randomized into no SLNB group and SLNB group.

NAUTILUS study aim to establish the minimally invasive treatment of breast cancer by reexamining the necessity of sentinel lymph node biopsy among patients with invasive breast cancer who have tumors under 5cm, are clinically node-negative, and are having breast conserving surgery performed.

Full description

[Background] Skipping ALND, the follow-up treatment in SN-positive patients, has non-inferior oncological outcomes compared to SLNB-only group, given that there is no severe SN metastases.

Axillary ultrasound can effectively exclude high nodal burden, showing 95% NPV in a systematic review.

SLNB has morbidity including lymphedema, limited range of motion, pain, and other post-surgical complications, eventually leading to reduced quality of life.

Considering improvement of imaging modalities and adjuvant care, survival outcome of SLNB must be re-evaluated. Especially research reflective of the regional specificities of Korea and Asia-Pacific is needed.

[Study design] Prospective, Multicenter, RCT.

[Statistical considerations] According to Z0011 trial, 5yr DFS in eligible patients is expected to be 86%, which is between previous data of 88.6% in cT1,2 and SN-negative patients4, and 83.9% in cT1,2 and 1-2 SN-positive patients.

Non-inferiority margin is set at 5%. With 5% significance level and 80% power, 780 patients are needed in each group. Assuming a 10% drop out rate, 1734 patients need to be recruited.

[Screening and Randomization] Participants undergo screening tests that assess eligibility according to inclusion/exclusion criteria.

In order to identify axillary lymph node metastases, axillary ultrasound is first performed by radiologists. Patients showing normal features are enrolled, while for conditionally normal patients, with only 1 suspicion of low nodal burden, axillary lymph node biopsy should be performed. Suspicious patients are excluded under following conditions: patients with 1 or more suspicion of high nodal burden, 2 or more suspicion of low nodal burden, or T2 invasive lobular carcinoma patients with 1 or more low nodal burden. The severity of nodal burden is defined through the criteria.

Patients who underwent radiological axillary staging are randomly assigned (1:1) to the study arm and the control arm before surgical care. Stratification is done based on trial centers and tumor sizes.

[Post-surgical care] All patients are planned to receive ipsilateral whole breast radiation. Patients randomized to non-SLNB arm are recommended to follow high tangential radiotherapy protocol, in which upper margin of radiation field includes axillary level I and II or lies within 2CM from humeral head.

Additional treatment may be performed if deemed necessary by the researcher

[Objectives]

1. Primary objective

   • 5yr invasive Disease Free Survival

2. Secondary objectives

   • 5yr Overall Survival
   • 5yr Distant Metastasis Free Survival
   • Axillary recurrence rate
   • Patient reported AE
   • QoL

Enrollment: 1,734 patients

Sex: Female

Ages: 19+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Women ≥ 19 years
• Invasive unilateral breast carcinoma with histological confirmation
• History of invasive breast cancer
• Histologically or radiologically no suspicion of distant metastases
• Performance status corresponding to ECOG grade 0-2
• Tumor size clinically and radiologically ≤ 5cm, independent of hormone receptor and HER2 status
• Clinically and sonographically negative axillary lymph nodes before biopsy; core needle biopsy or fine needle aspiration of suspicious lymph node required
• BCS candidate with postoperative whole-breast irradiation and adequate systemic therapy
• No psychological and geographical restriction in follow-up
• Written informed consent

Exclusion criteria

• History of any cancer in the previous 5 years
• Bilateral breast cancer
• Invasive breast cancer treated with neoadjuvant therapy
• Tumor size clinically and radiologically > 5cm
• Mastectomy candidate
• Pregnancy and breastfeeding
• Male breast cancer
• Unable to understand and fill out questionnaires

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,734 participants in 2 patient groups

No SLNB group

Experimental group

Description:

The study arm - BCS without SLNB

Treatment:

Procedure: No SLNB

SLNB group

Other group

Description:

The Control Arm - BCS with SLNB(+/-ALND)

Treatment:

Procedure: SLNB