The standard treatment for locally advanced cervical cancer is CTRT. We tested in a RCT whether outcomes could be improved by NACT-surgery.
Patients with clinical stages IB2, IIA or IIB squamous cervical cancer were randomized (stratified on stage) to either NACT-surgery arm comprising 3 cycles of paclitaxel (175 mg/m2) and carboplatin (AUC 5-6) every 3 weeks followed by radical hysterectomy or CTRT arm comprising standard pelvic radiation with 5 cycles of cisplatin (40 mg/m2) once per week. Post-operative radiation was given as per protocol criteria. Primary end point was disease-free survival (DFS, relapse or death whichever earlier) while secondary end points were overall survival (OS) and toxicity. The trial was designed to demonstrate 10% absolute increase in 5-year DFS in NACT-surgery arm, assuming 65% DFS in CTRT (control) arm (2-sided α = 0.05, power=80%) with planned sample size of 730.
Trial accrual was stopped after 635 patients were randomized between September 2003 and February 2015, of whom there were 2 eligibility violations. In remaining 633 (316 NACT-surgery, 317 CTRT, intent-to-treat population) there were 113 (17.9%) IB2, 158 (25.0%) IIA and 362 (57.2%) stage IIB patients. The arms were balanced for stage, age, haemoglobin, performance status and radiological pelvic lymph node status. At time of analysis (data cut-off 30 March 2017) median follow-up was 58.5 months; number of DFS events and deaths in NACT-surgery arm were 105 and 80 and those in CTRT arm were 87 and 80, respectively. There was no significant difference between NACT-surgery and CTRT with respect to 5-year DFS (67.5% vs. 72.2%, respectively, hazard ratio [HR] = 1.299, 95% CI 0.977-1.725, P = 0.07) and 5-year OS (74.8% vs. 74.7%, respectively, HR = 1.025, 95% CI 0.752-1.398, P = 0.87). NACT-surgery was not superior to CTRT in DFS and OS after adjusting for prognostic factors. Toxicity in two arms was acceptable with some differences in pattern.
Neoadjuvant chemotherapy followed by radical surgery is not superior to cisplatin based concurrent chemoradiation in locally advanced squamous carcinoma of cervix.
Clinical trial identification
Legal entity responsible for the study
Tata Memorial Centre
Department of Atomic Energy-Clinical Trials Unit, Tata Memorial Centre, Mumbai
All authors have declared no conflicts of interest.