Comparison of Concurrent Cisplatin Chemoradiotherapy Plus Adjuvant Chemotherapy Versus Concurrent Chemoradiotherapy Alone in Locally Advanced Cervical Cancer

Abstract

According to NCCN guidelines, concurrent chemoradiation (CCRT) is the standard care for locally advanced cervical cancer (LACC) patients , but the benefit of adjuvant chemotherapy (ACT) after CCRT for LACC patients is still controversial. This study is designed to answer the question by comparing the efficacy and toxicities of concurrent chemoradiation (CCRT) with adjuvant chemotherapy (ACT) (CCRT+ACT) versus concurrent chemoradiation (CCRT) alone in LACC. Patients with stage IB2,IIA2,IIB-IVA (2009 FIGO staging) cervical cancer were recruited from June 2013 to June 2018 at 4 cancer centers in China. The patients were randomly assigned to two arms: CCRT +ACT and CCRT alone. All patients were treated with IMRT (external-beam radiotherapy up to 50.4 Gy) with concurrent cisplatin, followed by intra-cavitary brachytherapy. The chemotherapy consisted of concurrent cisplatin(40 mg/m2 weekly) during IMRT, and 3 cycles of adjuvant CT with TP (docetaxel 75 mg/m2, day 1, and cisplatin 25 mg/m2, day 1-3 or carboplatin AUC 4-5 ,day 1)every 3 weeks. The primary endpoint was progression free survival(PFS), and the secondary endpoints included overall survival (OS), locoregional recurrence rate, distance metastasis rate , and toxicities. Survivals were calculated with Kaplan-Meier method. The differences between survivals were calculated with Log-rank test. Toxic effects were analyzed using the χ2 test. All statistical tests were two-sided. A total of 176 patients were recruited in the study and 161 were eligible for intent-for-treat analysis. 82patients were assigned to the CCRT+ACT arm and 79 in the CCRT alone arm. With a median follow-up of 60.1 months, the 5-year PFS and OS of all the patients were 68.32% and72.05%, respectively. The 5-year PFS was 75.61% in the CCRT+ACR arm, and was 60.76% in the CCRT arm. There was significant difference in PFS between the two arms （P=0.043). The 5-year OS was 76.83% in the CCRT+ACT arm and was, and was 67.09% in the CCRTarm. There was no significant difference in OS between the two arms （P=0.169). There was significant difference between the CCRT+ACT and CCRT arms in distant alone recurrence (p=0.048),but not in locoregional recurrence rate (p=0.752).There were significantly higher acute systemic side effects in the CCRT+ACT arm, especially the incidence of grade 3-4 hematologic and gastrointestinal reactions (P =0.000). Most of locoregional recurrence and distant metastases occurred with staging IIIB-IVA patients in the CCRT alone arm. Adjuvant chemotherapy after concurrent cisplatin chemoradiation for LACC patients improves PFS but not improves OS. It reduces distance metastasis but is correlated with poorer response to locoregional recurrence.There were more significant toxicities during adjuvant chemotherapy but it was well tolerated by patients. Further research and longer follow up is needed, especially for the staging IIIB-IVA LACC patients.