The role of adjuvant chemoradiation is not as well defined in vulvar carcinomas with lymph node metatstasis, as in other squamous cell carcinomas, such as carcinoma of the cervix and anal canal. This is probably due to low incidence of this disease. Han et al compared the survival rates in a group of 54 patients who received chemoradiation or radiation alone as primary treatment or as an adjuvant. Survival was found to be better in patients receiving chemoradiation, though the difference was not statistically significant.58

Considerable efforts have been made to conduct clinical trials investigating the potential benefits of adjuvant chemoradiation. But unfortunately, these trials had to be stopped due to poor patient recruitment.


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Radical chemoradiation

Most of the patients with vulvar carcinoma, especially in countries like India, present as advanced inoperable tumor. In an Indian series, about two-thirds of the patients were found to present in advanced stage (stage III–IV) of the disease.59 In such patients and in others, whose comorbidities and other factors make them unsuitable for surgery, definitive chemoradiation or brachytherapy are the possible options. In a first GOG Phase II study, chemoradiation with cisplatin and 5-fluorouracil was investigated for patients with advanced vulvar cancer.60 A total of 33.8% patients achieved complete remission. In a subsequent GOG Phase II study, chemoradiation with weekly single-agent cisplatin was studied. Complete clinical response was seen in 66.8% subjects and 50% reached complete pathologic remission with acceptable toxicity.61 Following these encouraging results, weekly cisplatin may probably be used for chemoradiation although mitomycin C and 5-flurouracil could also serve as alternative regimens. Tans et al showed complete response rates of 30%–70%.62

Neoadjuvant treatment in advanced vulva cancer

The concept of neoadjuvant chemoradiation followed by surgery seems promising and an attractive option in advanced vulvar carcinomas. Chemoradiation may downsize tumor volume, and hence help achieve resectability of the tumor.63 Radical and mutilating surgeries such as anterior or posterior exenteration may also be avoided following this. However, no randomized trials have been carried out to study this option. According to a recent Cochrane review of 3 published studies, it is suggested that there is no significant difference in overall survival rates or treatment-related adverse events when chemoradiation (primary or neoadjuvant) is compared with primary surgery in locally advanced vulvar carcinoma, bulky stage III–IV.64

A prospective multicenter trial in Bueno Aires found that the use of neoadjuvant chemotherapy in selected groups may improve operability, hence favoring organ preservation. Adverse reactions were acceptable in this trial, and local adverse effects that were expected after radiotherapy were also avoided.65 Aggressive neoadjuvant chemoradiation had been studied by GOG 101 for patients with unresectable T2 and T3 lesions. Of the operated patients, 46.7% had complete response at the time of surgery and 2.8% had residual disease that was still unresectable. This treatment could be promising in large midline tumors, where surgery may cause loss of clitoris and sphincter functions.66 GROINSS V-II , an ongoing trial is looking at whether it is safe to give radiotherapy instead of surgery in sentinel node-positive patients as surgery followed by post-operative radiation leads to increased morbidity. 

Management of recurrences

Identifying the important prognostic factors for recurrences and giving appropriate adjuvant therapy in designated cases and a close follow-up can help in prevention and early diagnosis of recurrences. An increased risk of recurrence has been seen in patients with LN metastases, large size of the tumors, deep invasion, lymphovascular invasion, and close surgical margins. Adequate management of recurrence is determined by its site whether local, groin, or distant. In an 8-year audit at our institute,67 there were 17 recurrences (21.7%). The 2-year disease-free survival was 100% in those with no nodal involvement, 73.5% in those with unilateral nodal disease, and 60% in those with bilateral nodal involvement. A majority of patients with local recurrence underwent resurgery and flap reconstruction followed by radiation therapy in those cases where it was not given before. Patient with groin recurrence had a worse prognosis and excision of the involved nodes was followed by radiation therapy. Distant metastasis was dealt with by chemotherapy.

CONCLUSION

Management of vulvar cancer is mainly determined by the tumor stage at initial diagnosis and the prognostic factors. This review is an attempt to give an overview of the current literature and studies on vulvar carcinoma, highlighting previous protocols as well as exploring the future directions of management. Due to the low incidence of the disease, the level of evidence for the various treatment modalities is very scarce. In locally advanced vulvar cancers, the role of neoadjuvant chemotherapy or chemoradiation seems attractive. In early cancers also, organ preservation protocols need to be developed. Hence, prospective controlled trials are urgently required to improve the outcomes in this relatively rare yet aggressive disease.

Disclosure

The authors report no conflicts of interest in this work.

Swarupa Mitra,1 Manoj Kumar Sharma,1 Inderjeet Kaur,1 Ruparna Khurana,1 Kanika Batra Modi,2Raman Narang,1 Avik Mandal,1 Soumya Dutta1
1Department of Radiation Oncology, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India, 2Department of Genitourinary Surgical Oncology, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India

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Source: Cancer Management and Research.
Originally published January 9, 2018.