Patient characteristics
Between June 2007 and January 2017, 388 patients with LACC who underwent treatment in 6 cancer centers were retrospectively analyzed. The patient and tumor characteristics are summarized in Table 1. The mean ± SD age of these patients was 51.3 ± 9.5 years. FIGO stage was IB2 in 35 patients (9%), IIA2 in 47 patients (12%), and IIB in 306 patients (79%). The histological type squamous cell carcinoma was observed in 336 patients. Radical chemoradiotherapy with cisplatin based EBRT plus brachytherapy was received by 278 patients. All patients completed the full course of radiotherapy and two cycles of concurrent chemotherapy. 287 patients received no further adjuvant chemotherapy after CCRT.
NACT involved a combination of 3–4 cycles of cisplatin plus paclitaxel regimen in all 110 patients. Using this treatment, 65 patients received radical hysterectomy, whereas 45 patients received chemoradiotherapy. No significant differences were found between the two groups in baseline characteristics.
Clinical response
After 3–4 cycles of NACT with cisplatin plus paclitaxel, 9 patients (7%) had complete response (CR) and 79 (72%) had partial response (PR). The CR and most PR patients who required radical operation received radical resection. For patients with stages IB2 and IIA, 77.5% (31/40) received surgery, whereas only 51.4% (36/70) received surgery for IIB stage. The patients with PR and stable disease (SD) were not considered amenable to receive radical surgery, and so received CCRT as radical treatment. Three months after radiotherapy, the CR and PR were 98.3% (115/117) in the Standard group, 100% (65/65) in the Surgery group, and 97.7% (44/45) in the Neo-Ra group (Table 2) (p > 0.05).
Patterns of treatment failure
The median follow-up of survivors was 66.5 months (range 8-212 months). For 5-year follow-up period, locoregional relapse occurred in 3.2% in Standard group, 1.5% in Surgery group and 11.1% in Neo-Ra group (p > 0.05), whereas a disseminated relapse occurred in 14.4% patients in Standard group, 7.7% in Surgery group and 11.1 % in Neo-Ra group, where were considered similar (Table 2) (p > 0.05) .
Late toxicities
Acute toxicities during radiotherapy were well tolerated by entire group of patients. Hematological and gastrointestinal toxicities were most commonly observed adverse events. The most common side effect that occurs due to late toxicity was gastrointestinal toxicity, which occurred in 24.5% of patients. Most of them were grade 1 or 2 adverse events. The grade 1–3 gastrointestinal toxicities were seen in 23% cases in Surgery group, 18% cases in Neo-Ra group, and 26% cases in Standard group, respectively, showing no significant difference. No patient had grade 4 adverse events. Genitourinary toxicities were the second most common late side effects, which occurred in 14% of patients. Most of them were grade 1–2, and grade 1–3 genitourinary toxicities were seen in 11% cases in Surgery group, 4% cases in Neo-Ra group, and 16% cases in Standard group, respectively, which showed no significance either (Table 2). Other less common late side effects included vaginal dehiscence and dyspareunia, but are less observed.
Survival analysis
The 5-year OS was observed in 92.5% patients in Surgery group, and in 84.9% in Standard group, which showed no significant differences, but both groups had higher rates than that of 75.6% patients in Neo-Ra group (p < 0.05). The 5-year DFS and PFS were 89.2% and 87.7 % in Surgery group, 77.8% and 77.8% in Neo-Ra group, and 81.7% and 80.9% in Standard group, respectively, and showed no significant differences among any groups (Fig. 1 A-C).
Subgroup analysis showed that, for IB2 and IIA2 stage, the 5-year OS was 90.3%, 88.9% and 83.3%, the DFS was 87.1%, 88.9% and 85.7%, and PFS was 84.1%, 88.9% and 83.3% for Surgery group, Standard group and Neo-Ra group, respectively, showing no significant differences among any groups for the three alternative modalities (Fig. 1 D-F). For IIB stage, the 5-year OS in the Neo-Ra group (72.2%) was significantly lower than the Surgery group (94.1%) and the Standard group (85.5%). The 5-year DFS was 91.2%, 75.0%, 80.9% and PFS was 91.2%, 75.0%, 80.5% for Surgery group, Standard group and Neo-Ra group, showing no significance among any groups (Fig. 1 G-I). The results of IIB stage were similar with the results of the whole group.
Prognostic factors
The various potential prognostic factors for predicting DFS, PFS and OS rates included age, maximum diameter of tumors, treatment days and mean D90 HRCTV (EQD210), SCC, CA125, WHO histology, overall stage, tumor regression, lymph node metastasis, parametrial involvement and adjuvant chemotherapy. In multivariate analysis, tumor regression (CR vs. PR + SD + PD), pathological type (squamous cancer vs. non- squamous cancer) and lymph node metastasis (positive vs. negative) were found as independent predictors of OS. Furthermore, besides the above factors, the maximum diameter of tumors and adjuvant chemotherapy were considered as significant prognostic factors for DFS and PFS (Table 3–5).