Patients And Baseline Characteristics
Of the 206 patients, 126 had 2009 stage IB2, 80 had stage IIA2. The mean age of the patients was 46 years (range 22–69 years). Pathological type distributions were as follows: squamous carcinoma, 174; non-squamous carcinoma, 32. Of all the patients, 104, 53 and 49 cases were classified into the PST, NAC + RS and CCRT groups, respectively. No significant difference was detected in surgical approach between the PST and NAC + RS groups. Table 1 list the clinical characteristics of the patients.
Table 1
Characteristics | PST (n = 104) | NACT (n = 53) | CCRT (n = 49) | P |
Age(years) | | | | 0.090 |
>45 | 54 | 27 | 34 | |
≤ 45 | 50 | 26 | 15 | |
Hemoglobin | | | | 0.077 |
≥ 115 g/L | 52 | 25 | 33 | |
<115 g/L | 52 | 28 | 16 | |
FIGO Stage | | | | 0.054 |
IB2 | 70 | 33 | 23 | |
IIA2 | 34 | 20 | 26 | |
Differentiation degree | | | | 0.357 |
Grade1 | 4 | 1 | 0 | |
Grade2 | 72 | 40 | 39 | |
Grade3 | 28 | 12 | 10 | |
Histology Type | | | | 0.072 |
SCC | 82 | 47 | 45 | |
Non-SCC | 22 | 6 | 4 | |
Surgical Approach | | | | 0.082 |
Laparotomy | 82 | 35 | - | |
PST Primary surgical treatment, NACT + RS Neoadjuvant chemotherapy followed by radical surgery, CCRT Concurrent chemoradiotherapy, FIGO Federation of Gynecology and Obstetrics, SCC Squamous carcinoma; Non-SCC Non-squamous carcinoma |
High-risk factors (HRFs) predictive of supplement treatment
Less patients in NAC + RS group had deep cervical stromal invasion than those in the PST (P = 0.024). No differences in lymph node metastasis, intravascular tumor embolus and vaginal margin were observed between PST and NAC + RS group (P = 0.734, P = 0.704 and P = 0.487, respectively). There was no difference in the rate of postoperative supplement treatment (P = 0.714) (Table 2).
Table 2
Postoperative HRFs associated with pathology
Characteristics | PST n (%) | NACT + RS n (%) | P |
Lymph node metastasis | | | 0.734 |
Negative | 81 (77.9) | 40 (75.5) | |
Positive | 23 (22.1) | 13 (24.5) | |
Intravascular tumor embolus | | | 0.704 |
No | 90 (86.5) | 47 (88.7) | |
Yes | 14 (13.5) | 6 (11.3) | |
Vaginal margin | | | 0.487 |
Negative | 102 (98.1) | 51 (96.2) | |
Positive | 2 (1.9) | 2 (3.8) | |
Deep stromal invasion | | | 0.024 |
No | 25 (24.0) | 22 (41.5) | |
Yes | 79 (76.0) | 31 (58.5) | |
Supplemental treatment | | | 0.714 |
Non-treatment | 30 (28.8) | 11 (20.8) | |
Radiotherapy | 27 (26.0) | 15 (28.3) | |
Chemoradiotherap | 43 (41.3) | 24 (45.3) | |
Chemotherapy | 4 (3.9) | 3 (5.6) | |
HRFs High-risk factors, PST Primary surgical treatment, NACT + RS Neoadjuvant chemotherapy followed by radical surgery |
Survival Analysis
The median follow-up time was 57 months (range 4-104 months). 28 patients died: 13 in PST group, 8 in NAC + RS and 7 in CCRT. The median time of death of the 28 patients was 14 months (range 6–33 months). For all patients, the 3-year OS was 86.4%. There was no significant difference in the three groups (PST: 87.5%, NAC + RS: 84.9%, CCRT: 85.7%, P = 0.843 ) (Fig. 1).
Patterns Of Treatment Failures
There were 32 patients who experienced treatment failures. Local recurrence was observed in 13 patients (4 in PST, 7 in NAC + RS and 2 in CCRT, respectively) after a median time of 14 months (range 10–33 months) in PST, 9.5 months (range 6–29 months) in NAC + RS, 10 months (range 8–15 months) in CCRT, respectively. 12 patients experienced distant metastasis (6 in PST, 3 in NAC + RS and 3 in CCRT, respectively) after a median time of 14 months (range 10–27 months) in PST, 9 months (range 6–29 months) in NAC + RS, 14 months (range 7–21 months) in CCRT, respectively. Local recurrence and distant metastasis were presented in 7 patients (4 in PST, 1 in NAC + RS and 2 in CCRT, respectively) after a median time of 12 months (range 10–14 months), 29 months and 11 months (range 8–15 months), respectively. For all patients, the 3-year DFS rates were 84.0%. There was no significant difference in the three groups (PST: 85.6%, NAC + RS: 79.2%, CCRT: 85.7%, P = 0.414) (Fig. 2).
Acute And Late Toxicities
The most frequently observed acute toxicities were hematologic side effects. 11 patients (11.5% ) in PST, 12 ( 27.9% ) in NAC + RS and 17 (39.5%) in CCRT experienced grade 3–4 leukopenia (P = 0.248). 10 patients (10.4%) in PST, 11 (25.6%) in NAC + RS, 12 (27.9%) in CCRT underwent grade 3–4 neutropenia (P = 0.435). 3 (3.1%) in PST, 1(2.3%) in NAC + RS, 1 (2.3%) in CCRT suffered grade 3–4 thrombocytopenia (P = 0.116). 4 ( 4.2% ) in PST, 11 (25.6%) in NAC + RS, 6 (14.0%) in CCRT had grade 3–4 anemia (P = 0.190). No grade 3–4 hepatotoxicity and nephrotoxic were observed. Detail data was shown in Table 3. Grade 3–4 late toxicity mainly consisted of lower extremity lymphedema (4/104, 3.8%), bowel obstruction (3/104, 2.9%) and thrombosis (1/104, 1.0%) in PST, lower extremity lymphedema (5/53, 9.4%) and bowel obstruction (1/53, 1.9%) in NAC + RS and radiation-induced rectitis (4/49, 8.2%) and femoral head necrosis (1/49, 2.0%) in CCRT. No grade 5 toxicities were observed. There was no significant difference in cumulative late adverse effects rate in the three groups (P = 0.777).
Table 3
Frequency of acute toxicities
Toxicity | PST n (%) | NACT + RS n (%) | CCRT n (%) | P |
G1-2 | G3-4 | G1-2 | G3-4 | G1-2 | G3-4 | - |
Leukopenia | 30 (31.3) | 11 (11.5) | 17 (39.5) | 12 (27.9) | 22 (51.2) | 17 (39.5) | 0.248 |
Neutropenia | 21 (21.9) | 10 (10.4) | 12 (27.9) | 11 (25.6) | 24 (55.8) | 12 (27.9) | 0.435 |
Thrombocytopenia | 6 (6.3) | 3 (3.1) | 3 (7.0) | 1 (2.3) | 17 (39.5) | 1 (2.3) | 0.116 |
Anemia | 9 (9.4) | 4 (4.2) | 7 (16.3) | 11 (25.6) | 10 (23.3) | 6 (14.0) | 0.190 |
Hepatotoxicity | 5 (5.2) | 0 | 4 (9.3) | 0 | 5 (11.6) | 0 | 0.931 |
G Grade, PST Primary surgical treatmen, NACT + RS Neoadjuvant chemotherapy followed by radical surgery, CCRT Concurrent chemoradiotherapy |
Hospitalization Time And Cost
The average hospitalization time was 49.72 days in PST, 63.08 in NAC and 54.22 in CCRT, respectively ( P = 0.000 ). The patients in NAC + RS needed longer hospitalization time than those in PST (P = 0.000) but had same length of stay as those in CCRT (P = 0.07).The average hospitalization expenditure was $7969.77 in PST, $9915.97 in NAC + RS, and $7646.62 in CCRT, respectively (P = 0.000). NAC + RS had increased hospitalization cost compared with PST (P = 0.000) and CCRT (P = 0.000). Detail data was shown in Table 4.
Table 4
Length of hospital stay and hospitalization expenditure
| PST (n = 104) | NACT + RS (n = 53) | CCRT (n = 49) | P |
Hospitalization time(days) | 49.72 ± 19.40 | 63.08 ± 15.26 | 54.22 ± 8.50 | 0.000 |
Hospitalization expenditure($) | 7969.77 ± 3115.07 | 9915.97 ± 2553.34 | 7646.62 ± 2872.94 | 0.000 |
PST Primary surgical treatment, NACT + RS Neoadjuvant chemotherapy followed by radical surgery, CCRT Concurrent chemoradiotherapy |