Options for surgical trials in vulva cancer.

Henry Kitchener, University of ManchesterANZGOG, March 2013

Role of surgery in early vulval cancer

To effect a cure by preventing recurrence.

Small tumours (straightforward)

Large tumours (more complex)

To preserve vulval function and avoid chronic lymphoedema.

Aims of surgery To excise the primary tumour and

minimise risk of local recurrence

To excise groin nodes (uni or bilateral)

To stage, in order to plan adjuvant treatment, assess margins

To avoid disfigurment

Conservation of function

Plastic procedures

Sentinel node surgery in vulval cancer

Photographs courtesy of Dr Cath Holland

Evidence base from Cochrane Reviews of surgery for VIN and early cancer. VIN. (Pepas et al, 2011) One RCT of laser vs ultrasonic surgical aspiration. 30 patients; underpowered for primary outcome.

Early cancer (Ansink et al 1999) No adequate RCT’s. 3 observational studies. Radical local excision is safe (margin >8mm) Contralateral groin node dissection is unnecessary in

lateralised disease. Superficial groin node dissection is unsafe.

Note: Some studies rejected because early cancer could not be separated, and treatment not uniform.

Track record of surgical research in vulval cancer. Generally sparse Lack of RCT’sBut Surgery has been improved greatly by

incremental change Triple incision in the 1980’s Ipsilateral groin node dissection in the 1990’s Sentinel node dissection in the 2000’s

Approach has been “Innovate without increasing hazard”

Vulval cancer surgery

1960's 1980's 2000's

More radical

Enbloc radical vulvectomy (Way)

Challenges for surgical trials in vulval cancer.

Disease is rare

Survival is generally good

Many cases are easily managed

In problem cases, surgery may not be the solution

Vulval cancer: What do we know? It exists in two forms

HPV related (basiloid)

Lichen sclerosis related (differentiated)

Basiloid

Preceded by VIN3 whereas (differentiated) arises more spontaneously

May be more widespread and difficult to resect conservatively

Trend has been toward younger women (HPV, smoking)

HPV vaccination will protect

Vulval cancer: What else do we know?

Disease presents at an earlier age.

40-50% are HPV related.

Groin node dissection and RXT can result in considerable morbidity.

Sentinel node detection could avoid the need for most groin node dissections.

Chemoradiation can achieve dramatic responses but can have marked late effects

Role of surgery in VIN 3

To deal effectively with VIN 3 Unifocal (easy) Multifocal (difficult)

To preserve vulval function May not be feasible with widespread disease

and there is a risk of recurrence.

But, would anti-HPV strategies be more effective?

Antiviral Therapy

Imiquimod HPV Vaccines Photodynamic therapy

50 – 60% response rates Need to get rid of HPV 16

Trial in VIN3Problem: Widespread VIN3

Hypothesis: Eradication of widespread VIN3 may be facilitated by antiviral therapy followed by completion surgery

Intervention: Antiviral therapy followed by surgery

Control: Antiviral therapy

Outcome: Time to progression

Power: Based on superiority (based on 50% recurrence)

Conclusion

VIN3/vulval cancer surgical trials are challenging.

Need GCIG collaboration.

Role of completion surgery following antiviral therapy offers a potential trial setting