Invasive Vulvar Neoplasm

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Several histologic types of invasive vulvar carcinoma include squamous cell carcinoma, Paget's disease, basal cell carcinoma, melanoma, Bartholin gland carcinoma, and sarcoma. Treatment for all these types is similar.

Surgery is the primary treatment for invasive vulvar cancer. Historically, en bloc vulvectomy was the standard of care. This procedure includes vulvectomy and inguinal and upper femoral node dissection. However, en bloc vulvectomy results in severe genital disfigurement and is accompanied by a high incidence of treatment-related complications, including 1% to 5% mortality rates (154). Currently, more conservative surgical techniques are preferred and are equally effective in limited, non-aggressive disease. Farias-Eisner, et al. (155) reported similar survival rates when comparing patients with Stage I and Stage II disease after treatment with conservative versus radical vulvectomy. Nonetheless, in advanced, aggressive disease, radical vulvectomy may be necessary.

Alternatives to surgery include radiotherapy and/or chemotherapy. Chemotherapy alone is of limited efficacy in vulvar cancer, but the combination of chemotherapy and radiotherapy appears effective (147). Radiation (142) and chemoradiation (146) can also be adjuvants to surgery. For patients with any stage of vulvar carcinoma who are unable to undergo surgery, radical radiation (147) alone may enhance survival.

Local surgical excision with wide or radical margins is treatment of choice for Stage I vulvar carcinoma (140,141). With less than 1 mm stromal invasion, fewer than 1% of cases are complicated by inguinofemoral lymph node metastases, and this procedure alone is adequate (139). Mohs microsurgery allows for complete removal of the primary lesion.

For more invasive Stage I lesions (> 1 mm), the risk of nodal metastases is 8% and additional unilateral lymphadenectomy is suggested (147). Ansink, et al. (156) authored a systematic review of two nonrandomized case-controlled observational studies investigating the effect of surgical treatment in early squamous cell carcinoma of the vulva (cT1-2N0M0 tumors). With lateralized, node-negative disease, radical local excision with complete ipsilateral lymphadenect-omy appears effective. Both studies reported similar recurrence rates in local excision as compared with radical vulvectomy (157,158). One nonrandomized case-controlled study supports that ipsilateral dissection is as effective as bilateral dissection (157). Alternatively, for central lesions, bilateral lymphadenectomy is indicated (139). When resecting nodes, it is imperative to take both iliac and femoral nodes; one study found that leaving the femoral nodes resulted in a 4% groin recurrences (146). Though not first-line treatment, LEEP and CO2 laser may be acceptable alternatives to conventional surgery (138).

Three-incision conservative or radical vulvectomy with bilateral inguino-femoral lymphadenectomy is used to treat Stage II disease (139). Five-year survival rates are 80% to 90% (131). Survival and disease-free interval are similar for modified radical vulvectomy and en bloc radical vulvectomy (159). Both LEEP and CO2 laser may be acceptable alternatives (138).

For Stage III vulvar cancer, radical vulvectomy with inguinal and femoral lymphadenectomy is the currently accepted first-line therapy (139). In a randomized trial, participants with two or more positive nodes who underwent radical vulvectomy and bilateral inguinal and femoral groin node dissections showed significantly better survival with postoperative groin and pelvic irradiation than with pelvic node dissection (142). Therefore, if nodes are positive, it is currently accepted practice to add pelvic and groin irradiation. A study investigating the role of radiation alone showed recurrence rates of 10% in patients with Stage III/IV disease (142), proving that radiation alone is an unacceptable alternative for surgery. It is, however, an appropriate therapy for patients who are unable to tolerate or are unsuitable candidates for surgery (142). Preoperative radiation therapy may improve operability and decrease the extent of surgery required (147). Chemoradiation as pretreatment before surgical excision may lessen tumor burden, allowing for more conservative excision. In a Phase II study by the Gynecologic Oncology Group, Moore et al. (146) over 97% of patients treated with combination therapy were free of disease. Alternatively, chemora-diation can be used as primary treatment for vulvar cancer (145). Trials have resulted in complete response rates of 53% to 89% and disease-free survival rates of 47% to 84%, with a median follow-up of 37 months (147).

Chemotherapeutic agents with demonstrated effectiveness in combination with radiation include 5-FU, cisplatin, mitomycin C, bleomycin, methotrexate (139). Disadvantages of combination therapies include multiple complications due to each individual intervention, as well as the risk for cumulative toxicity.

Surgical management of Stage IV vulvar cancer is radical or en block vulvectomy and lymphadenectomy and removal of metastases (139). With two or more positive nodes, surgery followed by radiation has better survival than postoperative pelvic node dissection (134). Preoperative radiation (147) or chemoradiation (146) may decrease the tumor size and the extent of surgery required. Chemoradiation (145) alone is an acceptable alternative to surgery. For those intolerable of or unsuitable for surgery or chemotherapy, radical radiation therapy alone may increase survival (147).

Close follow-up is necessary to detect recurrence. Without nodal involvement, the five-year survival rate after radical local excision is up to 75%. Inguinal recurrences may require vulvectomy. Radiation or chemoradiation may be used with or without surgery for palliation.

There is no standard treatment for metastatic disease. If distant metastases are present, salvage cytotoxic chemotherapy with cisplatin, methotrexate, bleomycin, mitomycin C, and cyclophosphamide may be appropriate (139). Prognosis is poor.

Verrucous carcinoma is a squamous cell carcinoma variant treated with wide local excision (160). If node positive, lymphadenectomy should be performed, as well. Radiation is contraindicated because it may induce anaplastic transformation and increase the likelihood of metastases (161).

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