Clinical Characteristics
In all, we enrolled 301 cervical cancer patients who were with two intermediate risk factors. Among them, 156 patents received adjuvant chemo-radiotherapy, while the rest of 145 patents received adjuvant radiotherapy alone. Compared to patients who received adjuvant radiotherapy alone, those who received chemo-radiotherapy presented no difference in clinical tumor stage, tumor size, lympho-vascular involvement, deep stromal invasion and follow-up. However, patients who did receive adjuvant concurrent chemotherapy tend to be younger than those who did not (Table 1).
Table 1
Patient Demographics and Baseline Tumor Characteristics
Variable | Adjuvant chemo-radiotherapy (n = 156) | Adjuvant radiotherapy (n = 145) | p value |
Age, year | | | 0.046 |
median | 60 | 63 | |
Stage | | | 0.752 |
IA2 | 4 | 5 | |
IB1 | 88 | 82 | |
IB2 | 11 | 13 | |
IIA1 | 36 | 35 | |
IIA2 | 17 | 10 | |
LVSI | | | 0.562 |
yes | 66 | 67 | |
no | 90 | 78 | |
DSI | | | 1.000 |
yes | 132 | 122 | |
no | 24 | 23 | |
Tumor size | | | 0.526 |
≥ 4 | 114 | 101 | |
< 4 | 42 | 44 | |
Risk group | | | 0.787 |
large Tumor + DSI | 90 | 78 | |
large Tumor + LVSI | 24 | 23 | |
DSI + LVSI | 42 | 44 | |
Follow up, months | | | 0.932 |
median | 56.9 | 56.6 | |
Abbreviation: DSI, deep stromal invasion; LVSI, lymph-vascular space invasion; SCC, squamous cell carcinoma; |
Survival Analysis for the whole group
During the follow up, for the whole group, there were 40 patients who died. The 5-year overall survival in the adjuvant chemo-radiotherapy and adjuvant radiotherapy groups were 90.29% and 81.29%, respectively (Fig. 1, Table 2). No significant difference was showed in overall survival between the two groups Fifty-six patients suffered recurrence, of them, local recurrence was found in 13 patients, distant metastasis was showed in 28 patients and 15 patients were with both local and distant recurrences. The common metastatic sites were liver, lung, bone and lymph nodes. Compared to patients who did not received adjuvant chemotherapy, those who did acquired better disease-free survival (86.11% vs 74.89%, p = 0.004) ((Fig. 2, Table 2).
Table 2
Survival for the Whole Group Patients
Group | Adjuvant chemo-radiotherapy (n = 156) | Adjuvant radiotherapy (n = 145) | P value |
3-year | 5-year | 3-year | 5-year |
OS | 96.15% | 90.29% | 91.02% | 81.29% | 0.060 |
DFS | 91.59% | 86.11% | 80.67% | 74.89% | 0.004 |
Abbreviations: OS = overall survival; DFS = disease-free survival. |
#: calculated by Kaplan–Meier method |
Survival Analysis for Patients with high Squamous Cell Carcinoma level
For patients with high squamous cell carcinoma level, there were 25 cases who died and there were 33 patients who developed recurrence. Nine patients were with local recurrence alone and 13 patients suffered from only distant metastasis. Additionally, 11 patients presented with both local and distant metastasis. Patients in the adjuvant chemo-radiotherapy group acquired better 5-year overall survival (87.8% vs 88.4%, p = 0.802) and disease-free survival (76.9% vs 80.4%, p = 0.556) than those in the adjuvant radiotherapy group (Figs. 3 and 4, Table 3). We also analyze the recurrence pattern, with result showing that there was no difference in local recurrence between groups with radiotherapy and chem-radiotherapy. However, distant metastasis was significantly higher in the radiotherapy group than that in the chemo-radiotherapy group (p = 0.036) (Table 4).
Table 3
Survival for the Patients with high SCC level
Group | Adjuvant chemo-radiotherapy (n = 84) | Adjuvant radiotherapy (n = 67) | p value |
3-year | 5-year | 3-year | 5-year |
OS | 94.05% | 90.72% | 86.57% | 73.41% | 0.015 |
DFS | 89.16% | 86.03% | 77.61% | 69.40% | 0.007 |
Abbreviations: OS = overall survival; DFS = disease-free survival. |
#: calculated by Kaplan–Meier method |
Table 4
Recurrence Patterns for Patients with high SCC level
Group | Adjuvant chemo-radiotherapy (n = 84) | Adjuvant radiotherapy (n = 67) | p value |
3-year | 5-year | 3-year | 5-year |
LR | 5(6.0%) | 7(8.3%) | 8(11.9%) | 10(14.9%) | 0.069 |
SM | 5(6.0%) | 6(7.1%) | 11(16.4%) | 18(26.9%) | 0.002 |
Abbreviations: LR = local recurrence; SM = systemic metastases |
#: calculated by Kaplan–Meier method |
Survival Analysis for Patients with low Squamous Cell Carcinoma level
For patients with low squamous cell carcinoma level, 23 patients recurred with 15 patents dying of tumor recurrence. Four patients recurred only locally, 15 patients had only distant metastasis and 4 patients developed both local and distant recurrences. The 5-year overall survival and disease-free survival in the adjuvant chemo-radiotherapy and adjuvant radiotherapy groups were 90.65%, 86.62% and 88.74%, 79.63%, respectively (Figs. 5 and 6, Table 5). No significant differences were found in both overall survival (p = 0.097) and disease-free survival (p = 0.253). Further analysis of recurrence pattern, results just showed that there were no differences in both the local and distant failure between patients did and did not receive adjuvant chemotherapy (Table 6).
Table 5
Survival for the Patients with low SCC level
Group | Adjuvant chemo-radiotherapy (n = 72) | Adjuvant radiotherapy (n = 78) | p value |
3-year | 5-year | 3-year | 5-year |
OS | 98.61% | 90.65% | 94.84% | 88.74% | 0.791 |
DFS | 94.36% | 86.62% | 83.27% | 79.63% | 0.146 |
Abbreviations: OS = overall survival; DFS = disease-free survival. |
#: calculated by Kaplan–Meier method |
Table 6
Recurrence Patterns for Patients with low SCC level
Group | Adjuvant chemo-radiotherapy (n = 72) | Adjuvant Radiotherapy (n = 78) | p value |
3-year | 5-year | 3-year | 5-year |
LR | 1(1.4%) | 3(4.2%) | 2(2.6%) | 5(6.4%) | 0.612 |
SM | 3(4.2%) | 8(11.1%) | 10(12.8%) | 11(14.1%) | 0.515 |
Abbreviations: LR = local recurrence; SM = systemic metastases |
#: calculated by Kaplan–Meier method |
Clinical predictors for disease-free survival, local recurrence-free survival and distant metastasis-free survival for patients with high Squamous Cell Carcinoma level
For patients with high squamous cell carcinoma level, results showed that tumor size and deep stromal invasion were independent predictors of disease-free survival and distant metastasis-free survival. Besides, adjuvant chemotherapy was found to be the unique factor significantly associated with distant metastasis-free survival, indicating that patients who received adjuvant chemotherapy suffered less distant failure than those who did not (Table 7).
Table 7
Multivariate Analyses of DFS, LRFS, and DMFS for Patients with high SCC level
Variable | DFS | LRFS | DMFS |
HR (95%CI) | p value | HR (95%CI) | p value | HR (95%CI) | p value |
Adjuvant chemotherapy Yes vs no | 0.456(0.217–0.957) | 0.038 | 0.538(0.207–1.401) | 0.204 | 0.282(0.111–0.721) | 0.008 |
Tumor size ≥4 cm vs < 4 cm | 2.988(1.278–6.984) | 0.012 | 3.213(1.426–7.335) | 0.007 | 1.731(0.701–4.276) | 0.234 |
DSI Yes vs no | 2.083(0.988–4.391) | 0.054 | 2.886(1.012–8.235) | 0.048 | 1.410(0.603–3.296) | 0.428 |
LVSI No vs yes | 0.645(0.319–1.302) | 0.221 | 0.610(0.241–1.541) | 0.296 | 0.658(0.288–1.501) | 0.319 |
Abbreviations: DFS, disease-free survival; LRFS, local recurrence-free survival; DMFS, distant metastasis-free survival; DSI, deep stromal invasion; LVSI, lymph-vascular space invasion; SCC, squamous cell carcinoma; |