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

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.

• Compare return to usual daily activities at 18 months between the groups [Срок оценки: 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. [Срок оценки: 30 months]
• Morbidity at 12 months after surgery. [Срок оценки: 12 months]
• Incidence of lower limb lymphoedema up to 30 months after surgery. [Срок оценки: 30 months]
• Cost and cost-effectiveness at 12 months post-surgery. [Срок оценки: 12 months]
• Fear of recurrence at baseline, 8 weeks, 6 months, 12 months, 18 months, 24 months, and 30 months. [Срок оценки: 30 months]
• Clinical accuracy of high-resolution ultrasound to predict groin lymph node involvement. [Срок оценки: 18 months]
• Disease-free survival (DFS) and overall survival (OS) at 30 months. [Срок оценки: 30 months]
• Determine compliance with serial ultrasound scans. [Срок оценки: 18 months]
• Utility of biomarkers to reliably reflect the presence or absence of positive groin lymph nodes, and explore novel biomarkers for vulvar cancer. [Срок оценки: Up to 15 years]