A Phase III Prospective Randomized Controlled Clinical Trial for the Efficacy and Safety of Neoadjuvant Chemotherapy Combined With Concurrent Chemoradiotherapy and Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer (Lump ≥4 cm).

PURPOSE/OBJECTIVE(S) The standard treatment for locally advanced cervical cancer was concurrent chemoradiotherapy. The effect of concurrent chemoradiotherapy was poor in locally advanced cervical cancer (lump ≥4 cm) (LACC) (lump ≥4 cm). We conduct this research in order to explore the role of neoadjuvant chemotherapy combined with concurrent radiotherapy in LACC (lump ≥4 cm). MATERIALS/METHODS A phase III, prospective, randomized controlled clinical trial was conducted at Guizhou Cancer Hospital. LACC (lump ≥4 cm) (FIGO 2018) were randomly divided into two groups, neoadjuvant chemotherapy combined with concurrent chemoradiotherapy (NACT+CCRT) group and concurrent chemoradiotherapy (CCRT) group. In NACT+CCRT group, patients were treated with paclitaxel cisplatin (TP) for 2 cycles, then they received concurrent chemoradiotherapy with TP for 2 cycles. In CCRT group, the patients were treated concurrent chemoradiotherapy with TP for 2 cycles. Tumor volume shrinkage, response rate and toxicity were the primary endpoints. Progression-free survival (PFS) and overall survival (OS) were the second endpoints. RESULTS Between March 2019 and December 2020, 97 patients randomly assigned (52 patients in the NACT+CCRT group and 45 patients in the CCRT group). In the NACT+CCRT group, after NACT, of evaluable 52, 52 responded: complete response (CR) 1(1.92%) and partial response (PR) 24(46.15%), stable disease (SD) 27(51.92%) and progressive disease (PD) 0(0%). 52 patients have completed CCRT, after NACT+CCRT, of evaluable 52, 52 responded: CR17(32.69%) and PR 35(67.31%), SD 0 and PD 0. In the CCRT group, 5 patients have not completed CCRT (because of the large tumor and concurrent radiotherapy not be tolerated), of evaluable 40, 40 responded: CR 8(20.00%) and PR 32(80.00%), SD 0 and PD 0. The immediate CR rate was better in NACT+CCRT than in the CCRT (P = 0.001). Treatment completion status: in the NACT+CRT group, all the patients (100%) have completed the NACT+CCRT, there were 40 (88.89%) patients have completed treatment (P = 0.013). In the tumor shrinkage, the median tumor volume after NACT was 33.91cm3 and 79.74cm3 in the CCRT group. There was significant difference between two groups (P = 0.000). Adverse event Hematological and gastrointestinal toxicity were most common. The Acute toxicities were hematological toxicity, gastrointestinal toxicity, there was no significant difference between two groups in the NACT+CCRT group versus the CCRT group (P>0.05). CONCLUSION NACT can minify the tumor volume of LACC (lump≥4cm) before CCRT and reduce the radiation dose of normal organs around the target area, thereby improved the completion rate of concurrent radiotherapy treatment. After NACT+CRT, the immediate response rate was improved significantly, especially the CR. However, there were more significant adverse events during NACT+CRT but it was well tolerated by patients. The high efficiency can be transformed into the advantage of prolonging survival or not, longer follow up and further research is needed. AUTHOR DISCLOSURE F. Li: None. J. Li: None. S. Yin: None. F. Mei: None. Y. Du: None. L. Hu: None. X. Tian: None. W. Hong: None. L. Shan: None. M. Liu: None. Y. Chen: None. W. Mao: None. J. Mu: None. B. Lu: None.