Premature adoption of adjuvant chemotherapy for locally advanced cervical carcinoma before the OUTBACK trial: cautionary tale on outcomes

Objective: The aim of this study was to investigate the use and outcomes of adjuvant chemotherapy for patients with locally advanced cervical carcinoma receiving definitive chemoradiation.

Methods: The National Cancer Database was accessed, and patients diagnosed between 2004 and 2015 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2-IVA disease who underwent definitive chemoradiation were selected. Patients who received radio-sensitizing single agent chemotherapy and those who received adjuvant multi-agent chemotherapy were identified. Overall survival was evaluated following generation of Kaplan-Meier curves while a Cox model was constructed to control for confounders.

Results: A total of 9895 patients were identified; 1003 (10.1%) received multi-agent adjuvant chemotherapy. Patients who received adjuvant chemotherapy were less likely to receive brachytherapy (60.9% vs 68.4%, p<0.001). Rate of adjuvant chemotherapy was higher among patients with stage IVA (18.1%) and stage III (11.9%) disease compared with those with stage II (8.4%) and stage IB2 (7.2%) disease (p<0.001). After controlling for confounders, administration of adjuvant chemotherapy was not associated with a survival benefit (hazard ratio 1.09, 95% confidence interval 0.98 to 1.20). Following stratification by disease stage, there was no survival benefit of patients who received adjuvant chemotherapy compared with those who did not; stage IB (p=0.002; 5 year overall survival 59.2% vs 74.9% favoring chemoradiation alone), stage II (p=0.41; 5 year overall survival 63.8% vs 67.6%, respectively), stage III (p=0.52; 5 year overall survival 48% vs 47.8%, respectively), or stage IVA disease (p=0.27; 5 year overall survival 29.5% vs 34.3%, respectively).

Conclusions: In the US, approximately 1 in 10 patients with locally advanced cervical carcinoma who underwent definitive chemoradiation also received adjuvant chemotherapy that was not associated with improvement in overall survival.