Featured IJGC Article Blog: Nov. 2016

Featured IJGC Article Blog: Challenges in the management of advanced vulvar cancer

By Jessica McAlpine, MD, FRCSC

This month’s issue of the International Journal of Gynecological Cancer includes two articles on non-surgical management of vulvar carcinomas (citations below). Natesan et al (Duke University, North Carolina) report on 25 vulvar cancer patients treated with chemoradiation therapy (CRT) for curative intent over a 20 year period in their center. They reported that 3 year overall survival was favorable at 71% with freedom from local and distant recurrence at 65% and 78%, respectively, with acceptable toxicities. They summarize that CRT is an effective option for women with advanced vulvar cancer with a thoughtful comment that selecting the ‘best’ patient remains a challenge.

Martinez-Castro and colleagues (Valencia, Spain) share a comprehensive review of the management of ‘inoperable’ locally advanced vulvar carcinomas from the 1970s to today. They are honest about the limitations of each treatment modality or combination and again cite challenges in selecting the ‘best’ patient for each option.

Not mentioned in either manuscript are the possible differences in outcomes and/or response to treatment within different subtypes of vulvar carcinoma. Although most cases reported in these papers are squamous cell carcinomas (vSCC) even within vSCC two distinct pathways of origin are now appreciated: HPV-associated and HPV-independent. We can usually identify these women when they come in to our clinics….the young woman who is a heavy smoker and you have been following in colposcopy clinic a decade earlier for abnormal cervical cytology, now with a vulvar lesion …in contrast to the older woman who has been given 5 non-specific skin creams over the past 3 years for her irritated and sore vulvar area. The first of course is an HPV-associated lesion; uVIN +/- vSCC, and the latter HPV-independent; dVIN +/-vSCC that has developed in a background of lichen sclerosis. Yet we are treating these women the same.
At the recent IGCS meeting in Lisbon, multiple abstracts on prognostic factors in vulvar carcinoma were presented. Two of the largest series demonstrated worse survival in HPV-independent tumors. Further distinction within HPV-independent tumors by p53 status was suggested with a trend for worse survival in HPV negative p53 aberrant vSCCs. But we still do not know how we should treat these patients differently; the optimal surgery/needed margin; adjuvant therapy; and surveillance?

I think we can learn a lot from our colleagues in head and neck cancers. For years, their treatment algorithms have been stratified according to HPV and smoking status. Specifically, head and neck surgeons work for greater surgical resection margins in HPV-independent tumors, and radiotherapy is believed to be less effective than observed in HPV-associated cancers.
It is interesting to note that in the Duke series, although no molecular features were examined, older age was associated with decreased overall survival and the majority of recurrences (particularly recurrences in very short time intervals) were observed in older women. I suspect these were mostly HPV-independent tumors. Distinguishing HPV status is easy (simple p16 IHC with DNA in situ hybridization where needed) and perhaps through collaborations with other centers who have data on primary CRT, we can determine the radiosensitivity of HPV-independent vs HPV-associated tumors.
I applaud and am grateful for the contribution of both of these articles as we all struggle to balance the morbidity of surgery and treatments with long term survival for these women. I look forward to an era of more clever stratification of women with vSCC; informing them of need for aggressive or less aggressive surgery, likelihood of response to CRT, and frequency of follow-up visits to the clinic. Health economic and patient quality of life differences will be apparent! In short, I hope we can do better.

Babatunde, O. A., Adams, S.A., Orekoya, O., Basen-Engquist, K., PhD & Steck, S. E. PhD. (2016). Effect of physical activity on quality of life as perceived by endometrial cancer survivors. International Journal of Gynecological Cancer, 26(9), 1727-1740. doi:10.1097/igc.0000000000000821
Natesan, D.B.S., Susko, M., Havrilesky, L. & Chino, J. (2016) Definitive chemoradiotherapy for vulvar cancer. International Journal of Gynecological Cancer, 26(9), 1699-1705. doi: 10.1097/IGC.0000000000000811