1 Introduction
Cervical carcinoma is a serious disease threatening many women and its incidence is the highest among the malignancies of the female reproductive system.[1] [2] [3]
Locally advanced cervical carcinoma refers to cervical carcinoma >4 cm and stage IB2 or IIA2. Surgery for these patients is difficult because of the large tumor, tumor invasion, and no clear boundary between the tumor and the surrounding tissues. Neoadjuvant chemotherapy (NACT) may improve the surgical resection rate for these patients. NACT is thought to inhibit tumor viability, reduce the surgical difficulty, improve the tumor resection rate, improve prognosis, and reduce metastasis.[4] [5] [6] [4]
Therefore, considering the controversy about the advantages of NACT in patients with massive cervical carcinoma combined with the health care issues of developing countries and patients’ wishes, the practical significance of NACT still need further exploration in these patients. Therefore, the present study reviewed the treatment and prognosis of NACT in Chinese patients with cervical carcinoma stage IB2 or IIA2. The results should provide direction for the diagnosis and treatment of cervical carcinoma in developing countries.
2 Material and methods
2.1 Study design and patients
This was a retrospective cohort study of patients who underwent type-C radical surgery and pelvic lymphadenectomy due to cervical carcinoma at stage IB2 or IIA2 between February 2014 and December 2016 at the Second Hospital of Jilin University. This study has been approved by the ethics committee of the Second Hospital of Jilin University. The need for individual consent was waived by the committee.
The diagnostic and staging criteria were based on the 2017 FIGO staging criteria.[4] [7]
The inclusion criteria were: cervical carcinoma at stage IB2 or IIA2; squamous cell carcinoma; tumor diameter >4 cm; 18 to 75 years of age; and type-C radical surgery and pelvic lymphadenectomy for cervical carcinoma were performed. The exclusion criteria were: preoperative radiotherapy; or positive parauterine tissues, positive margin, or positive para-aortic lymph nodes.
The patients were grouped according to whether the patients received NACT or not before surgery.
2.2 Neoadjuvant chemotherapy
All patients received TP regimens, namely paclitaxel (175 mg/m2 D1) + cisplatin (75 mg/m2 D1); paclitaxel (175 mg/m2 D1) + nedaplatin (80 mg/m2 D1); or paclitaxel (175 mg/m2 D1) + lobaplatin (30 mg/m2 D1); all based on 3-week cycles. NACT was generally performed for 1 to 3 cycles and the response was determined according to the objective remission rate (ORR) and the adverse reactions. Surgical treatment was usually performed 3 to 4 weeks after NACT.
2.3 Surgery
Surgery was performed by 2 or 3 senior associate chief surgeons (with >10 years of clinical experience). Type-C radical surgery for cervical carcinoma was performed routinely. Bilateral pelvic lymphadenectomy was performed. The range of lymphadenectomy included the internal iliac lymph nodes, external iliac lymph nodes, common iliac lymph nodes, obturator lymph nodes, and anterior sacral lymph node. All patients underwent pathologic examination after surgery, and the results were determined by the independent diagnoses of 2 senior pathologists. Tumor differentiation, vascular cancer emboli, tumor size, infiltration depth (>50%), and number of metastatic lymph nodes were recorded.
2.4 Postoperative treatment
The postoperative treatment regimen was based on the 2017 National Comprehensive Cancer Network (NCCN) guidelines.[8]
The postoperative radiation therapy was either intensity modulated radiation therapy or rotary volume modulated radiation therapy. The dose of external irradiation was 45 to 50.4 Gy/1.8 to 2.0 Gy/25 to 28 f. The synchronous sensitization chemotherapy regimen was cisplatin (40 mg/m2 ) once a week for 5 weeks. The postoperative chemotherapy regimen was the same as the preoperative NACT regimen.
2.5 Follow-up
All patients were followed up every 6 months after surgery. Follow-up was censored on July 31, 2018. Follow-up was performed by reexamination at the outpatient department. The patients underwent gynecologic physical examination, thinprep cytology test, pelvic magnetic resonance imaging, chest computed tomography, and abdominal color Doppler ultrasound. The time for relapse, metastasis, and death were recorded. Patients who were unable to return to the hospital for reexaminations were followed by telephone and the results of examinations at local hospitals were recorded. The diagnosis of postoperative local relapse and metastasis was based on physical examinations, imaging, and pathologic findings. The treatments after relapse were not included in this study.
2.6 Statistical analysis
Categorical data are presented as frequencies and were analyzed using the Chi-squared test. Continuous data are presented as mean ± standard deviation and were analyzed using the Student t test. Survival curves were plotted by the Kaplan–Meier method and analyzed using the log-rank test. The risk factors were assessed by Cox regression analysis. All analyses were performed using SPSS 19.0 (IBM Corp, Armonk, NY). Two-sided P -values <.05 were considered statistically significant.
3 Results
3.1 Baseline characteristics of patients
The characteristics of the 144 patients with locally advanced cervical carcinoma are shown in Table 1 . The follow-up duration was 28 to 55 months (median of 36.4 months). Of the 144 patients, 60 (41.7%) received NACT. The incidence of lymphatic space infiltration was lower in the NACT group (35.0% vs 58.3%, P = .006). The pathologic differentiation of patients in the NACT group was higher (P < .001). A total of 119 patients underwent postoperative radiation therapy, of which 97 received radiation therapy alone and 22 received radiation therapy combined with chemotherapy. The adverse reactions in the NACT group were mainly hematologic toxic reactions, but were tolerated. No grade ≥III adverse reactions were observed.
Table 1: Baseline characteristics of the patients.
3.2 Survival
Figure 1 shows that NACT did not significantly affect the progression-free survival (PFS; P = .453) and overall survival (OS; P = .933) between the 2 groups. The 1-, 2-, and 3-year PFS in the NACT and surgery groups were 93.3% vs 95.2%, 90.0% vs 92.9%, and 86.7% vs 90.5%, respectively (all P > .05). The 1-, 2-, and 3-year OS in the NACT and surgery groups were 96.7% vs 98.8%, 91.7% vs 96.4%, and 90.0% vs 89.3%, respectively (all P > .05).
Figure 1: Overall survival (OS) and progression-free survival (PFS) based on neoadjuvant chemotherapy vs no neoadjuvant chemotherapy before surgery. (A) OS (P = .933). (B) PFS (P = .450).
3.3 Multivariable analyses for OS and PFS
Table 2 presents the univariable and multivariable analyses of the factors associated with OS and PFS. The results showed that age, FIGO stage, positive lymph nodes, stromal invasion, lymphovascular space invasion, histologic grade, NACT, and postoperative treatments were not independently associated with OS or PFS (all P > .05).
Table 2: Univariable and multivariable analyses of OS and PFS.
4 Discussion
Locally advanced cervical carcinoma has a poor prognosis.[3] [6]
In 2017, the cancer survey report in China showed that the incidence of cervical carcinoma ranked first among gynecologic malignancies around the country.[2] [2] [8] [8] [3]
The results of this study suggest that NACT did not reduce the lymph node metastasis rate in patients with cervical carcinoma (P = .818). In addition, NACT did not influence the PFS (P = .184) and OS (P = .176) in patients with cervical carcinoma at stages IB2 and IIA2. Notwithstanding, the incidence of lymphatic space invasion was decreased in patients after NACT (P = .006), and the degree of pathologic differentiation was better (P < .001). NACT reduced the rate of postoperative radiation therapy and chemotherapy in patients. Over the past 3 years, the patients treated at our hospital were characterized by a relatively large number of patients with cervical carcinoma treated over a short period of time with relatively uniform treatment regimens. The current chemotherapy for cervical carcinoma is based on platinum combined with taxanes. The chemotherapy regimens were in line with standard treatment.[8] [9] [10]
Lee et al[11] [6] [12] [8] [13]
The results of the present study are supported by previous studies. Yang et al[14] [15] [16] [4]
In the present study, NACT did not bring advantages in OS and PFS. Harsh et al[17] [18] [19] [16] [20] [21–23] [23] [22] [24] [22]
This study has limitations. The number of patients was relatively small, the follow-up time was relatively short, and the combination of surgery and radiotherapy was relatively simple. For the value of NACT and the mode of treatment for patients with locally advanced cervical carcinoma, further large-scale, randomized clinical trials are needed.
5 Conclusion
Compared with patients who underwent surgery with/without radiotherapy and/or chemotherapy, NACT using paclitaxel and a platinum salt (cisplatin, nedaplatin, or lobaplatin) does not improve the prognosis and lymph node metastasis rate of locally advanced cervical carcinoma in Chinese patients.
Author contributions
Conceptualization: Linlin Liu.
Investigation: Wenxing Yan, Lihui Si, Yaming Ding, Shuang Qiu, Qi Zhang.
Methodology: Wenxing Yan, Lihui Si, Yaming Ding, Shuang Qiu, Qi Zhang.
Writing – original draft: Wenxing Yan.
Writing – review & editing: Linlin Liu.
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