No benefit of neoadjuvant chemotherapy followed by surgery in locally advanced cervix cancer: chemoradiation should remain the standard of care
Chemoradiation has been the standard treatment for patients with locally advanced cervical cancer since 1999 when it was shown to improve outcomes compared to radiation alone. Previous trials have found that neoadjuvant chemotherapy followed by surgery results in superior outcomes compared to radiation alone, but until now, there were no trial data comparing this strategy against standard chemoradiation. Results of a phase III trial comparing neoadjuvant chemotherapy (NACT) followed by radical surgery to standard cisplatin based concurrent chemoradiation now demonstrated that NACT-surgery does not lead to a better disease-free (DFS) or overall survival (OS). As such, chemoradiation should remain the standard of care in this setting.
In the presented phase III trial, 633 patients with clinical stages IB2, IIA or IIB squamous cervical cancer were randomized to either NACT-surgery arm comprising of 3 cycles of paclitaxel (175mg/m2) and carboplatin (AUC 5-6) every 3 weeks followed by radical hysterectomy or chemoradiation consisting of standard pelvic radiation with 5 cycles of cisplatin (40mg/m2) once per week. The primary endpoint of the study was DFS, defined as survival without relapse or death due to cancer, while secondary objectives consisted of OS and toxicity.
After a median follow-up of 58.5 months, the primary endpoint occurred in 30% of patients in the NACT-surgery group and 23% of patients in the chemoradiation group. The corresponding five-year DFS rates were 69.3% in the NACT-surgery group and 76.7% in the chemoradiation group (HR[95%CI]: 1.299[0.977-1.725]; p= 0.038). Also the 5-year OS rates were similar for both treatments at 74.8% for NACT-surgery and 74.7% for chemoradiation (HR[95%CI]: 1.025[0.752-1.398], p= 0.87).
In summary, this trial did not find a significant difference in DFS between the 2 treatment groups and even reported a trend for an increased DFS with chemoradiation compared to NACT-surgery. There was also no statistically significant difference in OS between the 2 groups. As such, chemoradiation should continue to be the standard treatment for patients with locally advanced cervical cancer. Currently, the European Organisation for Research and Treatment of Cancer (EORTC) is also running a trial comparing chemoradiation with neoadjuvant chemotherapy followed by surgery. Results of this study are expected in 2019.
S. Gupta S, Parab P, Kerkar R, et al. Neoadjuvant chemotherapy followed by surgery (NACT-surgery) versus concurrent cisplatin and radiation therapy (CTRT) in patients with stage IB2 to IIB squamous carcinoma of cervix: A randomized controlled trial (RCT). Presented at ESMO 2017, abstract 928O_PR.