Locally advanced vulvar cancer (LAVC) requires a multidisciplinary management. Based on the available evidence, radiotherapy, with or without concurrent chemotherapy, has a relevant role in neoadjuvant, adjuvant or exclusive treatments. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, in view of a better treatment personalization.
The 30% of VC patients presenting with locally advanced disease (T3/T4) may represent a problem regarding the treatment. Ultraradical surgery alone (radical vulvar operation combined with a partial or total pelvic exenterative-type procedure) is associated with a 4.3% mortality rate and 46% disease-free survival . However, although this is not well reported in the literature, there is significant physical and psychological morbidity resulting from these procedures due to a permanent colostomy, urostomy or both . In comparison with radical surgery, chemotherapy has been shown to be associated with poor survival and significant treatment-related toxicity . RT combined with chemotherapy, followed by organ-sparing surgery has shown efficacy in preventing stoma, but is also associated with significant wound-healing problems and treatment-related mortality . High-quality evidence on neoadjuvant RT was difficult to collect for several reasons, such as a small sample size, the heterogeneity of studies, and the use of different radio-chemotherapy schedules, RT dose fractionation, techniques, and target definitions. There was no evidence of a survival advantage or reduction in toxicity when neoadjuvant radio-chemotherapy was compared to primary surgery for women with locally advanced VC . In patients with large tumours that can only be treated with anterior and/or posterior exenteration, the complications of neo-adjuvant therapy might outweigh the complications of exenterative surgery. Neoadjuvant therapy is not justified in patients with tumours that can be adequately treated with radical vulvectomy and bilateral groin node dissection alone .
Age was a significant predictor of Overall Survival (OS) . When patients younger than the median age of 64 were compared to those >65 years, significant improvements in OS and Progression-Free Survival (PFS) were observed . Furthermore, age > 60 - 68 years had a negative impact on the entire response rate .
Adjuvant RT is indicated in patients with high risk factors, such as close/involved margins or inguinal lymph node involvement, to decrease the rate of recurrence, and thus improve OS, as shown in our results. Statistically significant improvements in OS and DFS according to low-stage and negative nodal status  were found, together with an improved LC in patients with close/involved surgical margins after adjuvant RT . Even in the adjuvant setting, we recorded high clinical outcome rates . These results, particularly in terms of LC, favorably compare with surgery alone. In fact, even in patients with early VC, surgical resection is associated with local recurrence rates of up to 40%. . Moreover, after surgery that affect tissues worsening tolerance, severe acute/late toxicity was reported in about one third of patients, mainly in terms of skin side effects.
The treatment with Interventional Radiotherapy (IRT) that allows for the delivery of a high radiation dose to the tumor, while sparing the surrounding, at-risk organs, with a very sharp dose fall-off, deserves special attention. It is well known that IRT is an effective treatment option for primary and recurrent VC, especially in patients with severe comorbidities and contraindications for surgery . Our analysis confirmed previous findings, which reported encouraging 5-year clinical outcomes, especially considering the preferential selection of most frail patients for IRT . Despite these positive data, IRT is rarely considered among the therapeutic options for locally advanced VC patients. It is likely that the rarity of this tumor, lack of widespread experience and expertise, and complexities in performing this treatment technique limit the use of IRT in the majority of RT centers . IRT could theoretically also be used as a boost after concurrent radio-chemotherapy to improve LC rates, especially in larger VCs. However, the role and real efficacy of IRT-based boost is largely unproven, with no prospective or randomized controlled trials available in this setting .
Most of the evidence on RT of VCs is low-level, based on retrospective studies. However, in different treatment settings, RT results are quite homogeneously encouraging even if there is clearly room for further improvements, in terms of both treatment outcomes and late sequelae and patient selection. These improvements may derive from prospective and possibly randomized studies, even if the rarity of VCs severely limits their feasibility. In parallel, or alternatively, the design of large databases could allow for the development of predictive models, which are particularly useful for defining individualized treatments based on tumors and patients’ characteristics. To date, the multidisciplinary management of these patients, based on tumor board discussion, represents the broader and more fruitful cooperation possible when choosing the best treatment for each patient.