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 cancer-related 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.
Between September 2003 and February 2015, 635 patients were randomised of whom 633 (316 in neoadjuvant chemotherapy-surgery group and 317 in concurrent chemotherapy-radiotherapy group) are included in final analysis with a median follow-up of 58·5 months. The 5-year disease-free survival in neoadjuvant chemotherapy-surgery group was 69·3% compared with 76·7% (95% CI, 71·6 to 81·8) in concurrent chemotherapy-radiotherapy group while the corresponding 5-year overall survival rates were 75·4% and 74·7%, respectively (hazard ratio 1·025, 95% CI, 0·752 to 1·398, p = 0·87). Early and delayed toxicities were acceptable in both groups with some difference in pattern.
Radiotherapy with concurrent cisplatin-based chemotherapy resulted in superior disease-free survival compared to neoadjuvant chemotherapy followed by radical surgery and should continue to be the standard of care in locally advanced cervical cancer.
Clinical trial identification
Legal entity responsible for the study
Tata Memorial Centre
Tata Memorial Centre - Government of India
All authors have declared no conflicts of interest.