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
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: High-resolution bilateral groin ultrasound monitoring.
- Who it may be relevant to
- Registry conditions: Vulvar Cancer Stage I, Vulvar Cancer Stage II, Lymph Node Metastasis, Groin Node. Basic parameters: from 18 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Australia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
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.
Interventions
- 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 se
Primary outcome measures
- Survival following the development of groin node metastasis (GNS, Groin Node-related Survival) at 30 months. [Time frame: 30 months]
Secondary outcome measures (10)
- Compare return to usual daily activities at 18 months between the groups [Time frame: 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. [Time frame: 30 months]
- Morbidity at 12 months after surgery. [Time frame: 12 months]
- Incidence of lower limb lymphoedema up to 30 months after surgery. [Time frame: 30 months]
- Cost and cost-effectiveness at 12 months post-surgery. [Time frame: 12 months]
- Fear of recurrence at baseline, 8 weeks, 6 months, 12 months, 18 months, 24 months, and 30 months. [Time frame: 30 months]
- Clinical accuracy of high-resolution ultrasound to predict groin lymph node involvement. [Time frame: 18 months]
- Disease-free survival (DFS) and overall survival (OS) at 30 months. [Time frame: 30 months]
- Determine compliance with serial ultrasound scans. [Time frame: 18 months]
- Utility of biomarkers to reliably reflect the presence or absence of positive groin lymph nodes, and explore novel biomarkers for vulvar cancer. [Time frame: Up to 15 years]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Australia · 9 centers
- John Hunter Hospital — Newcastle
- The Royal Darwin Hospital — Darwin
- The Wesley Hospital — Auchenflower
- St Andrew's War Memorial Hospital — Brisbane
- Royal Brisbane and Women's Hospital — Brisbane
- Buderim Private Hospital — Buderim
- Royal Adelaide Hospital — Adelaide
- Mercy Hospital for Women — Heidelberg
- … and 1 more center
Identifiers
NCT: NCT06476639 · ANVU