Objective
The objective of the study was to determine the long-term disease-free and overall survival outcomes of laparoscopic treatment of early-stage cervical cancer.
Study Design
This was a longitudinal study of prospectively registered patients of cervical cancer undergoing laparoscopic surgery from June 1994 to December 2005.
Results
A total of 139 patients were included, in which 60 patients were in International Federation of Gynecology and Obstetrics stage IA, 76 in IB, and 3 in IIA. Mean operation time was 231.1 ± 6.1 minutes. Median number of pelvic lymph node retrieval was 16. Major intraoperative complications included 1 great vessel injury, 1 ureteral injury, 1 colon injury, and 6 cystotomies. In a median follow-up of 92.1 months, the mean ± SEM cumulative disease-free and overall survival rates were 91.01% ± 2.77% and 92.78% ± 3.06%, respectively.
Conclusion
The laparoscopic approach has favorable long-term survival outcomes and perioperative morbidity. With the advantage of minimal invasiveness, laparoscopic treatment by experienced surgeons is an ideal alternative for early-stage cervical cancer.
Cervical cancer is the second most common cancer in women, with an estimate of 1.4 million cases worldwide. There were 493,000 new cases of cervical cancer and 274,000 deaths in 2002, 80% of whom lived in developing countries. In Taiwan, the Health and National Health Insurance Annual Statistics Information Service published 1828 new cases of cervical cancer and 792 deaths in 2006. Because of the popularity of the Papanicolaou smear, more cervical cancer can be diagnosed in the early stages. Surgical management, including radical hysterectomy and bilateral pelvic lymphadenectomy, is the treatment of choice in early cervical cancers, especially for stage IA2 and IB1 disease.
Laparoscopically assisted radical hysterectomy (LARH) with lymphadenectomy for the treatment of early cervical cancer was initially reported by Nezhat et al and Querleu, and several groups have reported its technical efficacy and safety since then. We noted that the LARH resulted in lower morbidity rates, including less blood loss, shorter hospital stay, and better quality of life for patients, in comparison with the open laparotomic approach, as was noted by other institutes or groups. However, few papers in the literature reported the results of its long-term follow-up. Therefore, the aim of this study was to identify the long-term recurrent and survival outcomes of performing LARH with pelvic lymphadenectomy for patients of early-stage cervical cancer.
Materials and Methods
This study was reviewed and approved by the Human Investigation Review Board of Chang Gung Memorial Hospital. All patients undergoing surgical management gave their written informed consent.
Patients
From June 1994 to December 2005, patients in Chang Gung Memorial Hospital who had histologically proved invasive cervical cancer at clinical stage no later than International Federation of Gynecology and Obstetrics (FIGO) IIA, without evidence of lymph node metastases in image studies, and who would like to undergo a hysterectomy with a laparoscopic approach were prospectively registered and followed up.
Patients in stage IA2 to IIA underwent type III hysterectomy procedures (radical hysterectomy), whereas patients in stage IA1 with the risk factors of lymphovascular space invasion (LVSI), multiple foci, or margin positive for carcinoma in situ (CIS) at conization with loop electrosurgical excision procedure (LEEP), underwent a type II hysterectomy (modified radical hysterectomy), according to the Piver-Rutledge-Smith classification.
Patients aged ≥70 years, with a body mass index (BMI) of ≥30 kg/m 2 , pregnancy, at status after pelvic/abdominal radiotherapy or in stage IA1 disease without the aforementioned risk factors who did not need radical hysterectomy, and/or with serious systemic diseases who were unsuitable for pneumoperitoneum and Trendelenburg position were not enrolled into the study.
Surgical techniques
Procedures of LARH and bilateral pelvic lymphadenectomy were performed according to the previously published procedures. In brief, a 10 mm laparoscopy was introduced via the skin incision at the middle point between the umbilicus and xiphoid process (Lee-Huang point) and 4 ancillary ports were made. Pelvic lymphadenectomy began above the bifurcation of the iliac vessels and extended to the level at which the ureter crosses over the common iliac artery with the monopolar scissor, followed by radical hysterectomy begun with Kleppinger bipolar forceps (Richard Wolf Instruments, Vernon Hills, IL). In later years, however, PlasmaKinetic pulsed bipolar system (Gyrus Medical, Maple Grove, MN) and LigaSure system (Valleylab Inc, Boulder, CO) were used instead of Kleppinger bipolar forceps, which resulted in less blood loss, shorter operation time, and less postoperative complications.
After pararectal and paravesical spaces were explored, uterosacral ligaments were transected with the Endo-GIA30 disposable surgical stapler (Auto-Suture, Norwalk, CT) using 30V staples, and bilateral parametria were coagulated and transected 2-3 cm lateral to the cervix. Then vaginal operation began as in the modified Schauta technique. Finally, the uterus with part of the vagina and paracolpium was removed en bloc. In earlier years, bilateral ureteral stents were used intraoperatively and removed postoperatively, but in later years this procedure was spared because of our acquaintance with the route of ureters.
Treatment protocol
Patients were discharged, according to our national regulations, with an afebrile status for at least 24 hours, no evidence of surgical complication, good wound healing, and full recovery of gastrointestinal function with satisfactory oral intake and stool passages. But the Foley catheter would remain indwelled for 3 weeks after surgery until a readmission for bladder training and removal of the Foley catheter. Patients were discharged if the amount of residual urine <50 mL. Patients would undergo postoperative adjuvant therapy if any high risk factors, including bulky tumor (≥4 cm in diameter), 50% depth or greater of cervical stromal invasion, positive surgical margins, microscopic parametrial involvement, lymph node metastases, and/or LSVI, were noted.
Patients were followed up every 3 months in the first 2 years, every 4 months in the third year, every 6 months in the fourth and fifth year, and annually thereafter, with pelvic examination, Papanicolaou smear, and serum markers of squamous cell carcinoma (SCC) antigen, carcinoembryonic antigen, or cancer antigen 125. If any suspicion arose, further imaging study, positron emission tomography scan, and tissue biopsy, where appropriate, would be performed. Although cancer recurrence was evident, salvage treatments including chemotherapy, radiotherapy, surgery, or combinations of different modalities, where appropriate, would be applied, and all the recurrences were documented with histopathologic confirmation.
Data analysis
Patient demographics, intraoperative findings, postoperative outcomes, and pathologic reports were prospectively recorded since the patient was enrolled into the study. Surgical outcomes including estimated blood loss, operation time, length of hospital stay, intraoperative and postoperative complications, and number of lymph node retrieval were all recorded. Age and BMI were considered as continuous variables, whereas parity and numbers of lymph node retrieval were considered as discrete variables.
Normality testing of data distribution was performed with the Kolmogorov-Smirnov test, in which data with normal distributions were presented as mean ± SEM, whereas data without normal distributions were presented as median value and interquartile (25th–75th percentile) range. Incidence was presented as a percentage, and range was given where suitable.
The Kaplan-Meier method was used to calculate the survival outcomes, including the disease-free survival and overall survival. The starting point was the date of surgery; the endpoint event was the recurrence of cancer in the calculation of disease-free survival and disease-related death in the overall survival analysis, respectively. The date of recurrence was defined on the proof of pathologic or radiologic report. All statistical calculations were performed using SPSS for Windows, release 11.5.0/2002 (SPSS Inc, Chicago, IL).
Results
From June 1994 to December 2005, a total of 139 patients with early cervical cancer undergoing laparoscopic radical hysterectomy and who were followed up for 3 years or longer were enrolled. The demographic backgrounds of these patients and tumors are presented in Table 1 . The study population was aged 48.1 ± 0.9 years and the mean BMI was 24.3 ± 0.3 kg/m 2 . In preoperative clinical staging, 135 patients (97.1%) were in FIGO stage IA or IB1. On pathologic examination, 119 patients (85.6%) had SCC, whereas 20 patients (14.4%) had LVSI, 39 patients (28.1%) were noted with deep stromal invasion, and 8 patients (5.8%) were noted with microscopic lymph nodal metastases ( Table 1 ).
| Characteristic | n |
|---|---|
| Age, y (mean ± SEM) | 48.1 ± 0.9 |
| Median parity, median (interqartile range) | 3 (2–4) |
| BMI, kg/m 2 (mean ± SEM) | 24.3 ± 0.3 |
| FIGO staging, n (%) | |
| IA | 60 (43.2) |
| IB1 | 75 (54.0) |
| IB2 | 1 (0.7) |
| IIA | 3 (2.2) |
| Histology, n (%) | |
| Squamous | 119 (85.6) |
| Adenocarcinoma | 11 (7.9) |
| Adenosquamous | 7 (5.0) |
| Lymphoepithelial | 2 (1.4) |
| Lymphovascular space invasion, n (%) | |
| Present | 20 (14.4) |
| Absent | 119 (85.6) |
| Stromal invasion, n (%) | |
| Absent or <50% | 100 (71.9) |
| 50% to <100% | 30 (21.6) |
| Full thickness (100%) | 9 (6.5) |
| Lymph nodal metastasis, n (%) | |
| Present | 8 (5.8) |
| Absent | 131 (94.2) |
Table 2 presents the surgery-related measurements. Mean operation time was 231.1 ± 6.1 minutes, and the median number of pelvic lymph node retrieval were 16 with 8 in each side. Mean blood loss was 666.0 ± 48.2 mL, and 61 patients (43.9%) underwent blood transfusion. Mean postoperative hospital stay was 8.1 ± 0.3 days at the initial surgery, and the hospital stay for bladder training and Foley catheter removal 3 weeks after was 5.4 ± 0.4 days.
| Outcome | n |
|---|---|
| Operation time, min | 231.1 ± 6.1 |
| Estimated blood loss, mL | 666.0 ± 48.2 |
| Blood transfusion, n (%) | 61 (43.9) |
| Pelvic lymph nodes retrieval, n; median (interquartile range) | |
| Right | 8 (6–11) |
| Left | 8 (6–11) |
| Hospital stay, d | 8.1 ± 0.3 |
| Bladder training, d | 5.4 ± 0.4 |
Intraoperative complications happened in 9 patients (6.5%) and are listed in Table 3 . One episode of left external iliac artery transection occurred at 2 cm below bifurcation of the left common iliac artery during pelvic lymphadenectomy. However, the anatomy was not identified until a complete hemostasis was achieved with electrocoagulation, and the cardiovascular surgeon was consulted to excise the nonviable portion and did an end-to-end anastomosis via laparotomy. Six cystotomies were all detected intraoperatively and repaired under laparoscopy. One ureteral injury happened at the ureterovesicle junction and the urologist performed an ureteroneocystomy with stenting via laparotomy. One rectal injury occurred because of severe endometriosis and was repaired successfully with laparoscopy.
