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12 Chemoradiation

12.1 Summary of available scientific evidence LoE 2+

Primary chemoradiation: as part of Cochrane systematic review, Shylasree et al.222 evaluated the
effectiveness and safety of neoadjuvant and primary chemoradiation for women with LAVC. Among
the 3 studies included in this review223-225, only two retrospective studies224,225 looked at primary
chemoradiation versus primary surgery. It should be noted that no pooled analysis is described. The
number of cases of tumour recurrence and deaths were too small in one study225 to allow computing
an adjusted hazard ratio (the confidence interval was non-informative for all combinations of
covariate adjustment). In the second retrospective study, Landrum et al.224 compared outcomes of 63
patients with LAVC treated by primary surgery (N = 30) of by primary chemoradiation (N = 33).
The general schema for chemoradiation involved weekly cisplatin (40 mg/m²) or two cycles of
cisplatin (50 mg/m²) plus 5-FU (1,000 mg/m²) concurrent with external beam radiation. The
radiation fraction size was generally 160-180 cGy delivered in a once-daily fraction with a median
dose of 4,760 cGy (range 3,690-6,300 cGy) to the whole pelvis and primary vulvar site, with
additional radiation to the inguinal regions as directed by nodal status. Patients were managed
surgically with radical (N = 11) or modified radical vulvectomy (N = 19) when adequate surgical
margins could be obtained without urinary or colonic diversion. Adjuvant radiation or
chemoradiation was completed in 19 of 25 patients in the primary surgery group with lymph node
metastasis. Eight patients had surgical excision of residual disease following primary
chemoradiation.

At a median follow-up of 31 months, there was no statistically significant difference in the risk of
death in patients with LAVC between patients who received primary chemoradiation and those who
received primary surgery, after adjustment for age, FIGO stage, size of tumour and nodal status (HR
= 1.09, 95% CI = 0.37-3.17, p > 0.05). Recurrence or PFS was not reported in a multivariate analysis
in this study. However, the authors reported no statistically significant difference in recurrence rate
based on treatment group (5 in the chemoradiation arm versus 7 in the primary surgery arm, p >
0.05). Four patients that were treated with primary chemoradiation only had a partial response to
treatment and died of the disease.

An another study enrolling at least 50 patients has been identified. In a GOG phase II study including
58 patients with LAVC not amenable to surgical resection (radical vulvectomy), Moore et al.226
assessed the efficacy and toxicity of radiation therapy and concurrent chemotherapy when used for
the primary treatment. Radiation was given daily, five days per week in 1.8 Gy fractions to a total
dose of 57.6 Gy. Patients received concurrent cisplatin (40 mg/m² to maximum dose 70 mg)
chemotherapy administered weekly throughout radiation therapy. Patients only underwent radical
surgical resection after chemoradiation if they had residual disease present on biopsy. After a median
follow-up of 24 months, 37 patients (64%) achieved a cCR. Among these patients there were 29
(50%) who underwent surgical biopsy and had a pCR (Table 9). Twenty-two of these 29 patients
continued to have no evidence of disease, while 7 patients experienced recurrence. Of the 29 patients
who had persistent disease after chemoradiation and who underwent surgical resection, 8 (28%) were
alive at last follow-up with no evidence of disease recurrence. Although acute toxicity was
significant, the protocol was considered tolerable.

Results from the 16 other identified studies227-242 are limited notably by the small number of patients LoE 3
evaluated (only 2 trials231,232 have accrued in excess of 20 patients) and by the heterogeneity in the

primary chemoradiation regimens. Although studies are small, chemoradiation as a primary

therapeutic approach has been reported to produce high response rates (Table 9).

Neoadjuvant chemoradiation: among the 3 studies223-225 included in the Cochrane systematic review LoE 1-
published by Shylasree et al.222, only one study223 looked at neoadjuvant chemoradiation versus

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