Neoadjuvant Chemotherapy Followed by Radical Surgery Versus Concomitant Chemotherapy and Radiotherapy in Patients With Stage IB2, IIA, or IIB Squamous Cervical Cancer: A Randomized Controlled Trial

Abstract

Purpose We compared the efficacy and toxicity of neoadjuvant chemotherapy followed by radical surgery versus standard cisplatin-based chemoradiation in patients with locally advanced squamous cervical cancer. Patients and Methods This was a single-center, phase III, randomized controlled trial ( ClinicalTrials.gov identifier: NCT00193739). Eligible patients were between 18 and 65 years old and had stage IB2, IIA, or IIB squamous cervical cancer. They were randomly assigned, after stratification by stage, to receive either three cycles of neoadjuvant chemotherapy using paclitaxel and carboplatin once every 3 weeks followed by radical hysterectomy or standard radiotherapy with concomitant cisplatin once every week for 5 weeks. Patients in the neoadjuvant group received postoperative adjuvant radiation or concomitant chemotherapy and radiotherapy, if indicated. The primary end point was disease-free survival (DFS), defined as survival without relapse or death related to cancer, and secondary end points included overall survival and toxicity. Results Between September 2003 and February 2015, 635 patients were randomly assigned, of whom 633 (316 patients in the neoadjuvant chemotherapy plus surgery group and 317 patients in the concomitant chemoradiation group) were included in the final analysis, with a median follow-up time of 58.5 months. The 5-year DFS in the neoadjuvant chemotherapy plus surgery group was 69.3% compared with 76.7% in the concomitant chemoradiation group (hazard ratio, 1.38; 95% CI, 1.02 to 1.87; P = .038), whereas the corresponding 5-year OS rates were 75.4% and 74.7%, respectively (hazard ratio, 1.025; 95% CI, 0.752 to 1.398; P = .87). The delayed toxicities at 24 months or later after treatment completion in the neoadjuvant chemotherapy plus surgery group versus the concomitant chemoradiation group were rectal (2.2% v 3.5%, respectively), bladder (1.6% v 3.5%, respectively), and vaginal (12.0% v 25.6%, respectively). Conclusion Cisplatin-based concomitant chemoradiation resulted in superior DFS compared with neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer.

Propensity Score Analysis of Radical Hysterectomy Versus Definitive Chemoradiation for FIGO Stage IIB Cervical Cancer

“…In fact, a recent RCT compared neoadjuvant chemotherapy followed by radical surgery versus CCRT for patients with FIGO stage IB2, IIA, or IIB, and the findings obtained showed that CCRT resulted in superior DFS over neoadjuvant chemotherapy followed by radical surgery. 11 However, the utilization rate of postoperative RTwas very low in that RCT (postoperative RT, 13.3%; postoperative CRT, 9.8%), although the majority of patients had FIGO stage IIB disease (57.2%). 11 Some possible reasons for the discrepancy between the results of that RCT and our results may be the difference of the patient and treatment characteristics such as utilization rate of postoperative RT, FIGO stage, and sample size.…”

“…11 However, the utilization rate of postoperative RTwas very low in that RCT (postoperative RT, 13.3%; postoperative CRT, 9.8%), although the majority of patients had FIGO stage IIB disease (57.2%). 11 Some possible reasons for the discrepancy between the results of that RCT and our results may be the difference of the patient and treatment characteristics such as utilization rate of postoperative RT, FIGO stage, and sample size. Therefore, prospective larger studies are needed to examine whether RH with adjuvant RT and definitive CRT are equivalent treatment options for patients with FIGO stage IIB cancer.…”

“…27 A recent RCT that compared neoadjuvant chemotherapy followed by radical surgery versus CCRT in patients with FIGO stage IB2, IIA, or IIB showed that CCRT resulted in superior DFS over that with neoadjuvant chemotherapy followed by radical surgery. 11 One of the advantages for surgery is the potential preservation of ovary function by ovarian transposition. However, the preservation rate of the functional outcomes of transposed ovaries varied among studies, whereas the location of transposed ovaries, body mass index, RT or CCRT as adjuvant therapy, radiation dose to the transposed ovaries, and age may be associated with the function of transposed ovaries.…”

“…10 A recent RCT compared neoadjuvant chemotherapy followed by radical surgery versus CCRT for patients with FIGO stage IB2, IIA, or IIB, and the findings obtained showed that CCRT resulted in superior disease-free survival (DFS) over neoadjuvant chemotherapy followed by radical surgery. 11 Because of the lack of data comparing primary RH with adjuvant RT versus CRT only for FIGO stage IIB cancer, we conducted PSM as an alternative method to compare the outcomes and toxicities observed in FIGO stage IIB cervical cancer patients treated by these 2 modalities.…”

Role of Neoadjuvant Chemotherapy in Treatment of Cervical Cancer: A Case Series of Thirty-Eight Patients Treated at Bangabandhu Sheikh Mujib Medical University in Dhaka, Bangladesh

“…In a prospective, randomized trial, there was no difference in recurrence or death rates for those patients who received NACT versus those who did not before undergoing a radical hysterectomy [31]. Most recently, a prospective, randomized trial of neoadjuvant chemotherapy followed by radical surgery versus standard cisplatin-based chemoradiation for patients with bulky local cervical cancers showed a superior disease free interval for the cisplatin-bases concurrent chemo radiation arm (76.7% versus 69.3% disease-free 5-year survival) [32]. In Bangladesh, 80% women present with advanced stage (Stage III -IV) cervical cancer, and this is fatal in this country [4].…”