Improved Survival with Definitive Chemoradiation Compared to Definitive Radiation Alone in Squamous Cell Carcinoma of the Vulva

Abstract

It is unclear whether definitive chemoradiation (CRT) results in improved survival compared to radiation therapy (RT) alone in patients with vulvar cancer who are not candidates for surgery. We compared these treatment strategies in the National Cancer Database (NCDB). Within the NCDB, 1352 patients with pathologically-confirmed squamous cell carcinoma of the vulva treated with definitive RT or definitive CRT between 2003-2014 were identified. Exclusion criteria were metastatic disease at diagnosis, palliative radiation dose (<4000 cGy), follow-up <6 months, and surgical treatment. The median age overall was 66 years (23-90 years). FIGO stage was distributed as follows: I (127, 9.4%), II (287, 21.2%), III (237, 17.5%), and IVA (701, 51.8%). Of the 1352 patients, 353 received RT and 999 received CRT. Chemoradiation was delivered as concurrent CRT (chemotherapy and RT start within 2 weeks apart) in 870 patients and sequential CRT (chemotherapy and RT start >2 weeks apart) in 129 patients. Median radiation dose was 5940 cGy (4000-7920 cGy). Clinical and tumor characteristics were compared using Chi-squared test and t-test. Survival outcomes after CRT or RT were compared using Kaplan-Meier method with log-rank test. Multivariate modeling with Cox proportional hazard model was performed to adjust for factors that may be associated with the decision to give chemotherapy. Planned subgroup analyses were also done based on age and stage to evaluate the effect of CRT in particular groups of interest such as elderly patients. Median follow-up was 42.6 months (6-131.6 months) for those patients alive at the time of last follow-up. The 5-year overall survivals were 44.2% for all patients and was significantly better in the CRT group compared to the RT group (49.9% vs. 27.4%, p<0.001). CRT was associated with decreased risk of death compared to RT in univariate analysis with a HR of 0.53 (0.46-0.63, p<0.001). CRT remained significant on multivariate analysis with a HR of 0.76 (0.63-0.91, p=0.003) after adjusting for age, race, insurance status, income, high school education, urban and rural region, Charlson-Deyo comorbidity score, year of diagnosis, and FIGO stage. The effect of CRT on overall survival was significant in FIGO II (p<0.001), FIGO III (p<0.004), and FIGO IVA (p<0.001), but was not observed in FIGO I (p=0.055). The effect of CRT on overall survival was evident in both patients with node positive (p<0.001), node negative (p<0.001) disease, and in patients >75 years old (p=0.04). This study demonstrates that definitive chemoradiation is associated with improved survival compared to radiation alone in patients with squamous cell carcinoma of the vulva who do not receive surgery. This result was evident in patients with FIGO II-IVA disease and in elderly patients. These findings suggest that chemoradiation should be considered for most patients in the definitive setting.