A Phase III Randomised Clinical Trial of Ultrasound Groin Monitoring Versus Groin Lymph Node Dissection to De-Escalate the Extent of Surgery in Vulvar Cancer (ANVU)

This study is a phase III, open label, multicentre, three-group, randomised clinical trial. The primary aim of this study is to determine whether intensive groin ultrasound monitoring (1) is effective and safe to replace invasive groin lymph node dissection (LND) to manage vulvar cancer, (2) decreases the morbidity associated with vulvar cancer surgery, and (3) is cost effective.

Study Overview

• Status: Not yet recruiting
• Conditions: Ultrasound Therapy; Complications; Lymph Node Metastasis; Groin Node; Vulvar Cancer Stage II; Vulvar Cancer Stage I
• Intervention / Treatment: Diagnostic test: High-resolution bilateral groin ultrasound monitoring

Detailed Description

Treatment of vulvar cancer causes significant morbidity. Despite being a rare cancer, at least 2500 survivors of vulvar cancer live in Australia. Most survivors live with the detrimental, life-long impacts resulting from their cancer treatment because there are currently no alternatives to mitigate these impacts. The personal and societal burden this entails is significant. To control such cancer-associated burden is a national priority.

Clinical palpation of the groin region and computed tomography (CT) scans do not reliably detect groin node involvement. Hence, current clinical guidelines recommend all women diagnosed at apparent Stage I or II have a surgical groin LND. This can be performed as a full IFL (full LND) to remove all groin nodes, or as a sentinel node biopsy (SNB) to remove selected (one or two) nodes. SNB is less invasive, however, is appropriate only for vulvar cancers <4cm in diameter and unifocal tumours (~50% of all Stage I and II vulvar cancers). SNB is also associated with a false negative rate (10%) that increases the risk of undetected nodes.

In 25% of cases (~80 Australian women per year), groin LND will reveal positive nodes (i.e., metastases), which triggers a referral for radiation treatment. If positive groin nodes are missed, and over time become enlarged, clinically palpable and attached to the overlying skin, >90% of women will die within 12 months, despite subsequent treatment. Conversely, if groin node involvement is detected early (e.g., by ultrasound) while still small, survival outcomes are excellent. Ultrasound technology is potentially as accurate as LND due to recent advances in resolution and technologies such as 2D/3D volumetric assessments and tissue flow. Furthermore, ultrasound is superior to medical resonance imaging (MRI), and to standard CT and positron emission tomography (PET) scans in capturing groin node involvement because it has a higher resolution, avoids harmful radiation and the technology is readily accessible outside of high-volume metropolitan areas.

The investigators propose to reduce surgical morbidity by replacing upfront groin LND for vulvar cancer patients with serial high-resolution ultrasound to detect groin metastases. Groin LND will only be necessary for the few women with ultrasound-detected metastases when they are still small. The ANVU trial will determine the value of serial groin ultrasound examinations in stage 1b and 2 vulvar cancer patients and whether it is feasible and safe to de-escalate the extent of vulvar cancer surgery to achieve improved outcomes for affected patients.

Women with this rare cancer bear an unacceptably high (and potentially avoidable) treatment-related burden. This clinical trial is the first step to address this problem in a novel yet pragmatic way. The potential overall outcome of ANVU could be a novel, less invasive alternative to vulvar cancer LND hypothesised to be associated with significantly less morbidity, without compromising survival.

• Study Type: Interventional
• Enrollment (Estimated): 640
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Brianna Armstrong; Phone Number: +61 7 3346 5063; Email: anvutrial@uq.edu.au
• Study Contact Backup: Name: Sara Baniahmadi; Phone Number: +61 7 3346 5073; Email: anvutrial@uq.edu.au

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2305
      • John Hunter Hospital
      • Contact: Anne Mellon; Email: anne.mellon@health.nsw.gov.au
      • Principal Investigator: Rachael O'Sullivan, MD
  • Northern Territory
    • Darwin, Northern Territory, Australia, 0810
      • The Royal Darwin Hospital
      • Contact: Michelle Harris, MD; Email: Michelle.Harris2@nt.gov.au
      • Principal Investigator: Michelle Harris, MD
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • The Wesley Hospital
      • Contact: Sara Baniahmadi; Phone Number: +61 7 3346 5073; Email: sara.baniahmadi@health.qld.gov.au
      • Principal Investigator: Andrea Garrett, MD
      • Sub-Investigator: Rhett Morton, MD
      • Contact: Brianna Armstrong; Phone Number: +61 7 3346 5063; Email: bri.armstrong@uq.edu.au
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
      • Principal Investigator: Andrea Garrett, MD
      • Contact: Sara Baniahmadi; Phone Number: 07 3346 5073; Email: s.baniahmadi@uq.edu.au
      • Contact: Brianna Armstrong; Phone Number: 07 3346 5063; Email: bri.armstrong@uq.edu.au
    • Brisbane, Queensland, Australia, 4000
      • St Andrew's War Memorial Hospital
      • Principal Investigator: Andreas Obermair, Prof
      • Contact: Brianna Armstrong; Phone Number: 07 3346 5063; Email: bri.armstrong@uq.edu.au
      • Contact: Sara Baniahmadi; Phone Number: 0733465073; Email: s.baniahmadi@uq.edu.au
    • Buderim, Queensland, Australia, 4556
      • Buderim Private Hospital
      • Principal Investigator: Andreas Obermair, MD
      • Contact: Sara Baniahmadi; Phone Number: 0733465073; Email: s.baniahmadi@uq.edu.au
      • Contact: Brianna Armstrong; Phone Number: 0733465063; Email: bri.armstrong@uq.edu.au
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
      • Principal Investigator: Martin Oehler
      • Contact: Martin Oehler; Phone Number: +61 8 8222 4816; Email: martin.oehler@adelaide.edu.au
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Mercy Hospital for Women
      • Contact: Adam Pendlebury, MD; Email: cgo@dradampendlebury.com.au
      • Principal Investigator: Adam Pendlebury
    • Parkville, Victoria, Australia, 3052
      • Royal Women's Hospital
      • Contact: Estefania Vicario; Email: estefania.vicario@thewomens.org.au
      • Contact: Niveditha Rajadevan, MD; Email: niveditha.rajadevan@thewomens.org.au
      • Principal Investigator: Niveditha Rajadevan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females, over 18 years, with histologically confirmed SCC or adenocarcinoma of the vulva
• Clinically stage 1b or 2 on medical imaging (CT or MRI scan of pelvis, abdomen, and chest), without evidence of regional or distant metastatic disease
• Willing and able to undergo IFL/SNB according to local clinical practice management guidelines
• Willing and able to comply with all study requirements, timing and/or nature of required assessments.
• Signed written informed consent
• Negative (serum or urine) pregnancy (BHCG) test ≤ 30 days of surgery ONLY in pre-menopausal women and women < 2 years after the onset of menopause.

Exclusion Criteria:

• Women with non-invasive vulvar conditions (e.g. non-invasive non-mammary Paget's disease)
• Clinical or medical imaging evidence of regional and/or distant metastatic disease
• Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)
• Other prior malignancies <5 years before inclusion, except for successfully treated keratinocyte skin cancers, or ductal carcinoma in situ
• Estimated life expectancy of ≤6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with normal/negative baseline groin ultrasounds - Intervention Group; Surgical removal of primary tumour and serial high-resolution bilateral groin ultrasound monitoring every 2 months for 12 months, and at month 15 and month 18, with clinical examination at 8 weeks, 4 months, 8 months, 12 months, 15 months, and 18 months (n=360).	Diagnostic test: High-resolution bilateral groin ultrasound monitoring; Participants in the Interventional Group will undergo surgical excision of the primary tumour, either via radical local excision or radical vulvectomy. Post-vulvar surgery, participants will receive a groin node ultrasound every 2 months for 12 months, and at month 15 and month 18, and a clinical examination at 8 weeks, 4 months, 8 months, 12 months, 15 months, and 18 months. Senior imaging specialists review bilateral ultrasound scans for positive lymph nodes or suspicious findings, promptly sending reports to the primary care physician and trial manager within 5 business days. If positive nodes are detected, participants will consult their primary care physician for options. Depending on clinical judgment, they may be referred for LND or continue with serial ultrasounds and clinical exams based on preference and clinician guidance.
No Intervention: Participants with normal/negative baseline groin ultrasounds - Standard Group; Surgical removal of primary tumour and upfront full groin lymph node dissection (LND) or sentinel node biopsy (SNB) based on clinician choice (according to local clinical practice management guidelines) (n=120).
No Intervention: Participants with suspicious/indeterminate baseline groin ultrasound - Standard Treatment; Participants with suspicious/indeterminate baseline groin ultrasound (third group) will receive an upfront full groin LND or SNB, consistent with the current standard treatment, according to local clinical practice management guidelines (n=160).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival following the development of groin node metastasis (GNS, Groin Node-related Survival) at 30 months.	Determine survival following the development of groin node metastasis (GNS, Groin Node-related Survival) in patients with vulvar cancer randomised to serial high-resolution groin USM compared to standard upfront surgical groin LND at 30 months.	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare return to usual daily activities at 18 months between the groups	Return to usual daily activities at 18 months measured using the PROMIS Ability to Participate in Social Roles and Activities Short Form 8a	18 months
HRQL and PROMS as measured by the EQ-5D and FACT-V at baseline, 8 weeks, 6 months, 12 months, 18 months, 24 months, and 30 months.	Compare Patient Reported Outcomes (PROMs) and Health Related Quality of Life (HRQL) between the groups.	30 months
Morbidity at 12 months after surgery.	Compare pain and adverse events (AEs) (morbidity) between the groups.	12 months
Incidence of lower limb lymphoedema up to 30 months after surgery.	Compare the incidence of lower limb lymphoedema at 30 months post-surgery between the groups.	30 months
Cost and cost-effectiveness at 12 months post-surgery.	Compare cost and cost-effectiveness between the groups.	12 months
Fear of recurrence at baseline, 8 weeks, 6 months, 12 months, 18 months, 24 months, and 30 months.	Compare fear of recurrence between the groups.	30 months
Clinical accuracy of high-resolution ultrasound to predict groin lymph node involvement.	Determine the diagnostic accuracy of standardised, high-resolution groin ultrasound to identify groin node metastasis.	18 months
Disease-free survival (DFS) and overall survival (OS) at 30 months.	Compare disease free and overall survival between the groups.	30 months
Determine compliance with serial ultrasound scans.	Compliance with serial ultrasound scans.	18 months
Utility of biomarkers to reliably reflect the presence or absence of positive groin lymph nodes, and explore novel biomarkers for vulvar cancer.	Assess the role of blood and tissue molecular biomarkers to accurately determine the burden of disease (positive lymph nodes) in vulvar cancer, assist with risk stratification and aid disease surveillance.	Up to 15 years

Collaborators and Investigators

• Sponsor: Queensland Centre for Gynaecological Cancer
• Collaborators: Royal Brisbane and Women's Hospital; The University of Queensland
• Investigators: Study Chair: Andreas Obermair, MD, Director, Queensland Centre for Gynaecological Cancer Research

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2035
• Study Completion (Estimated): December 31, 2035

Study Registration Dates

• First Submitted: June 17, 2024
• First Submitted That Met QC Criteria: June 23, 2024
• First Posted (Actual): June 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Vulvar Cancer; Ultrasound Therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Neoplastic Processes; Genital Neoplasms, Female; Vulvar Diseases; Neoplasm Metastasis; Pathological Conditions, Signs and Symptoms; Vulvar Neoplasms; Lymphatic Metastasis
• Other Study ID Numbers: ANVU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No