Vulvar cancer medical therapy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Overview
Radiation therapy and chemotherapy are usually not a primary choice of therapy but may be used in selected cases of advanced vulvar cancer. medical therapy Stage 0 Vulvar Cancer Traditionally, there were three grades of vulvar intraepithelial neoplasia (VIN). However, there is little evidence that all three grades are part of the same biologic continuum or that Grade 1 is even a cancer precursor. In 2004, the International Society for the Study of Vulvar Disease changed its terminology, reserving the designation VIN for two categories of lesions based on morphologic appearance:
Usual-type VIN: Human papillomavirus (HPV)-associated Grades 2 and 3 of warty, basaloid, or mixed histology, and usually occurring in young women. Differentiated-type VIN: non-HPV-associated Grade 3, and usually occurring in older women.
The term VIN 1 was eliminated. Disease that was previously called VIN 1 (grade I) is generally observed without definitive treatment.
High-grade VIN is usually managed with active therapy because of a higher risk for progression to invasive disease.[2] Estimates of progression rates are imprecise. A systematic literature review that included 88 untreated patients with VIN 3 reported a 9% progression rate (8 of 88 patients) to invasive vulvar cancer during 12 to 96 months of observation. In the same review, the spontaneous regression rate was 1.2%, all of which occurred in women younger than 35 years.[3] However, in a single-center study, 10 of 63 (16%) untreated women with VIN 2 or VIN 3 progressed to invasive cancer after a mean of 3.9 years.[4]
VIN lesions may be multifocal or confluent and extensive. It is important to perform multiple biopsies in treatment planning to exclude occult invasive disease. VIN located in nonhairy areas can be considered an epithelial disease; however, VIN occupying hairy sites usually involves the pilosebaceous apparatus and requires a greater depth of destruction or excision because it can track along hair roots.
Surgical Interventions
The principal treatment approach is surgical, but there is no consensus on the optimal surgical procedure. The goal is to remove or destroy the entire VIN lesion while preserving vulvar anatomy and function. Simple vulvectomy yields a 5-year survival rate of essentially 100% but is seldom indicated. Other more-limited surgical procedures, including separate excision of multiple lesions, are less deforming.[5] The choice of treatment depends on the extent of the disease and the preference or experience of the treating physician. There are no reliable data comparing the efficacy and safety of the various surgical approaches.
A systematic literature review identified only a single randomized trial comparing any of the surgical approaches.[2] In that trial, 30 women with high-grade VIN were randomly assigned to receive carbon dioxide (CO2) laser ablation versus ultrasound surgical aspiration (USA).[6] There were no statistically significant differences in disease recurrence, painful dysuria or burning, adhesions, or eschar formation between the two treatments after 1 year of follow-up. Scarring was observed in 5 of 16 women treated with laser ablation and 0 of14 women treated with USA (P < .01), but consequences of the scarring on sexual function or quality of life were not reported.[6][Level of evidence 1iiDii] The trial was too small to draw reliable conclusions about the relative efficacy of these surgical techniques. The remainder of the surgical literature is derived from case series and is prone to important study biases.[Level of evidence 3iiiD]
Whatever procedure is used, patients are at substantial risk of recurrence, particularly when the lesions are high grade or multifocal.[7] The most common sites of recurrence are the perianal skin, presacral area, and clitoral hood. About 4% of patients treated for VIN subsequently develop invasive cancer.[8,9]
Nonsurgical Interventions
Because of the physical and psychosexual morbidity associated with many vulvar surgical procedures, nonsurgical approaches have been studied. Some of these approaches, including topical 5-fluorouracil, gamma-interferon, bleomycin, and trinitrochlorobenzene, have been largely abandoned because of intolerable local side effects, such as pain, irritation, and ulceration, or high recurrence rates.[10,11] Photodynamic therapy, using topically applied 5-aminolevulinic acid as the sensitizing agent for 635 nm laser light, has also been studied. However, data are limited to small case series with variable response rates.[12,13][Level of evidence: 3iiiDiv]
More recently, among women with high-grade VIN, substantial response rates and acceptable tolerability were reported for topical imiquimod 5%, an immune-response modifier with activity in HPV 6/11-associated vulvar condylomata. Three randomized placebo-controlled trials (including a total of 104 patients) with clinical response as their primary endpoints.[Level of evidence: 1iDiv] have been reported in either peer-reviewed-journal or abstract format.[14-17] The results of these trials were summarized in a systematic review.[11] At 5 to 6 months, the complete and partial response rates in patients were 36 of 62 and 18 of 62 in the combined imiquimod arms versus 0 of 42 and 1 of 42 in the combined placebo arms (relative risk [RR], 11.95; 95% confidence interval [CI], 3.21–44.51).
In the only trial reporting progression to cancer (at 12 months), there was no difference in progression rate, but the trial was severely underpowered because only 3 of the total 52 women included developed invasive disease by 12 months.[16] The only trial reporting quality of life [16] showed no difference between imiquimod and placebo. Local side effects of imiquimod included pain, edema, erythema, and a single case of erosion. However, no patients had to discontinue treatment as a result of toxicity.
Standard treatment options:
Separate excision of focal lesions.[3] Wide local excision.[3] CO2 laser surgery and vaporization.[2,6] A disadvantage of vaporization is that it does not provide tissue for histologic examination to confirm complete removal of the lesion and the absence of invasive disease. Ultrasonic surgical aspiration (USA).[2,6] Superficial skinning vulvectomy with or without grafting.[3] Topical imiquimod for patients wishing to avoid surgery.[11,14-17]
Current Clinical Trials