Neoadjuvant chemotherapy plus surgery versus concurrent chemoradiotherapy in stage IB2-IIB cervical cancer: A systematic review and meta-analysis.

Panagiotis Balermpas,Wen Zou,Yang Zhang,Yeqian Feng,Yiyu Han,Haixia Zhang,Jingjing Wang,Chunhong Hu

doi:10.1371/journal.pone.0225264

Panagiotis Balermpas, Wen Zou + Show 6 more

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https://doi.org/10.1371/journal.pone.0225264

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Abstract

The optimal treatment strategy for stage IB2-IIB cervical cancer is controversial. This systematic review with meta-analysis evaluated the efficacy of concomitant chemoradiotherapy (CCRT) and neoadjuvant chemotherapy followed by radical surgery (NACT+S). Studies that evaluated NACT+S versus CCRT for patients with Federation of Gynecology and Obstetrics stage IB2-IIB cervical cancer were searched in MEDLINE, EMBASE, and the Cochrane Library database. Hazard ratios (HRs) with their respective 95% confidence intervals (CIs) were calculated using a random-effects model. Toxicity was also evaluated. Six qualified retrospective studies and one randomized controlled trial (2270 patients) were included in this review. The results suggested that compared with CCRT, NACT+S did not improve overall survival in all patients (HR 0.73, 95% CI 0.52–1.02) or stage IIB patients (HR 0.83, 95% CI 0.61–1.15). NACT+S did not improve disease-free survival (DFS) in stage IIB patients (HR 1.10, 95% CI 0.70–1.71). In the analysis of DFS in all patients, a high degree of heterogeneity was detected (I2 = 84%). Sensitivity analysis that eliminated these heterogeneous data suggested that CCRT could improve DFS over NACT+S (HR 1.47, 95% CI 1.12–1.93). Diarrhea and rectal and bladder complications occurred at a lower rate in the NACT+S group than in the CCRT group. NACT+S had no survival advantage for patients with stage IB2-IIB cervical cancer compared with CCRT but was associated with fewer side effects. Further prospective studies with a larger sample size of treatment protocols for locally advanced cervical cancer are needed.

Highlights

7 were excluded for the following reasons: research groups did not match, the study did not examine the outcome of interest, or the data were insufficient
The results suggested that neoadjuvant chemotherapy followed by radical surgery (NACT+S) did not improve overall survival (OS) compared with CCRT in the entire cohort (NACT+S vs. CCRT: Hazard ratios (HRs) 0.73, 95% confidence intervals (CIs) 0.52–1.02, P = 0.07), with median heterogeneity among the studies (P = 0.08, I2 = 45%; Fig 2)
The results suggested that Neoadjuvant chemotherapy (NACT)+S did not improve disease-free survival (DFS) compared with CCRT among all patients (NACT+S vs. CCRT: HR 0.94, 95% CI 0.57–1.56, P = 0.82); high heterogeneity was detected (P < 0.00001, I2 = 84%; Fig 4A)

Summary

Introduction

Treatment options for stage IB2-IIB cervical cancer. The treatment strategy for stage IB2-IIB, and especially stage IIB, cervical cancer is controversial. After five large randomized controlled trials in the 1990s [3], cisplatin-based concurrent chemotherapy and external pelvic irradiation followed by brachytherapy (CCRT) has been the preferred treatment option for patients with stage IB2-IIB cervical cancer. Most patients initially respond to this therapeutic approach, 22%-41% of patients still experience recurrence [4, 5]. This treatment is associated with early and long-term toxicities, including radiocystitis, radiation enterocolitis, vaginal stenosis, and pelvic adhesion. Neoadjuvant chemotherapy (NACT) followed by radical surgery (hysterectomy plus pelvic lymph node dissection) (NACT+S) is the most extensively researched treatment modality and has gained the most attention because it is considered to improve disease control and reduce toxicity

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