Cervical cancer remains a major health problem for women worldwide despite the availability of an effective method of screening. Cervical cancer is the third most common cancer and the fourth leading cause of cancer death among women worldwide.1 It is the sixth most common female cancer and the seventh leading cause of female cancer death in Korea.2,3 Although the therapeutic efficacy of radical hysterectomy and radiation therapy is equivalent,4,5 more than 80% of patients with early-stage cervical cancer undergo radical hysterectomy because this procedure is associated with fewer long-term complications and superior quality of life and sexual function compared with radiation therapy.6–8
Research shows that obesity is associated with a higher incidence of comorbid disease and a higher risk of perioperative complications.9,10 Therefore, many surgeons are reluctant to perform radical hysterectomy in obese women with early-stage cervical cancer. However, few studies have evaluated the outcome of radical hysterectomy in obese women, and further evaluation is therefore warranted.11–14 Several recent reports suggest that laparoscopic radical hysterectomy is a reasonable alternative to open radical hysterectomy because laparoscopic radical hysterectomy was associated with superior surgical outcomes, including less blood loss, lower transfusion requirements, more rapid recovery, and earlier hospital discharge, without any increase in perioperative complications or compromised survival.15–22 However, no study has compared the outcomes of laparoscopic radical hysterectomy and open radical hysterectomy in obese women with early-stage cervical cancer. The aim of the present study was to compare the surgical and oncological outcomes of laparoscopic radical hysterectomy and open radical hysterectomy in this population.
MATERIALS AND METHODS
Between 1998 and 2011, 166 patients with stage IA2–IIA2 cervical cancer and a body mass index (BMI, calculated as weight (kg)/[height (m)]2) of 30 or higher underwent laparoscopic radical hysterectomy (n=54) or open radical hysterectomy (n=112) at the Asan Medical Center in Seoul, Korea. The medical records of these patients were reviewed after obtaining the approval of the Asan Medical Center institutional review board.
Laparoscopic radical hysterectomy was performed as described previously.20 There are six gynecologic oncologic surgeons in the Asan Medical Center and all laparoscopic radical hysterectomy procedures were performed by these six gynecologic oncologic surgeons. For open radical hysterectomy, the surgical procedure and the extent of the surgical resection were identical to those of laparoscopic radical hysterectomy, except that a midline abdominal skin incision was made extending from the pubic symphysis to the supraumbilical area. After surgery, adjuvant radiation therapy was recommended to all patients with more than two intermediate risk factors, including large tumor size, deep stromal invasion, and lymphovascular space invasion.23 Adjuvant concurrent chemoradiation therapy was recommended to all patients with more than one high-risk factor, including parametrial involvement, lymph node metastasis, and resection margin involvement. However, some patients received adjuvant chemotherapy instead of radiation therapy or concurrent chemoradiation therapy at the discretion of the attending physician or at the patient's request after thorough discussion. In patients in whom lymph node metastasis or parametrial involvement is detected during surgery, the policy of the present authors is to complete laparoscopic radical hysterectomy or open radical hysterectomy with pelvic and para-aortic lymph node dissection and then administer postsurgery adjuvant concurrent chemoradiation therapy. After completion of treatment, patients were followed up every 3 months for the first 2 years, every 6 months for the next 3 years, and yearly thereafter.
Surgical and oncological outcomes in the laparoscopic radical hysterectomy and open radical hysterectomy groups were compared. A postoperative complication was defined as any documented adverse event occurring within 60 days of surgery. Postoperative febrile morbidity was defined as a documented body temperature of 38°C or greater on two occasions separated by an interval of at least 4 hours during the postoperative period, excluding the first 24 hours postsurgery. The return of bowel movement was defined as the passing of flatus and the return of bowel sounds. Postoperative bladder dysfunction was defined as any voiding difficulty requiring the reinsertion of a Foley catheter or clean intermittent catheterization regardless of the duration of catheterization. Postoperative mortality was defined as death from any cause occurring within 30 days of surgery. Frequency distributions were compared using χ2 and Fisher's exact tests. After using the Kolmogorov-Smirnov test to determine whether the data showed a normal or nonnormal distribution, the mean or median values of the two groups were compared using Student's t test or the Mann-Whitney U test. Disease-free survival was defined as the time, in months, from the date of laparoscopic radical hysterectomy or open radical hysterectomy to the date of relapse or censoring and overall survival was defined as the time, in months, from the date of laparoscopic radical hysterectomy or open radical hysterectomy to the date of death, last follow-up, or censoring. Disease-free survival and overall survival were estimated using the Kaplan-Meier method. Univariable analyses were performed to compare the two study groups; the log-rank test was used for categorical factors, and the Cox proportional hazards model was used for continuous factors. All prognostic variables showing significance in the univariable analyses were then included in a multivariable analysis involving the Cox proportional hazards model. P values of <.05 in the two-sided tests were considered significant. All statistical analyses were performed using SPSS 11.0 for Windows.
During the study period, 54 obese women (BMI 30 or greater) with stage IA2–IIA2 cervical cancer underwent laparoscopic radical hysterectomy and none required conversion to laparotomy. A total of 112 obese women underwent open radical hysterectomy. All patients underwent pelvic lymph node dissection. Twenty-three patients (42.6%) in the laparoscopic radical hysterectomy group and 73 patients (65.2%) in the open radical hysterectomy group also underwent para-aortic lymph node sampling or dissection (P=.006). Table 1 shows the characteristics of the study cohort. The mean BMI was 31.7 (range 30–38.67). No between-group differences were observed in any of the following: 1) demographic factors (including age, body weight, height, BMI, parity, medical disease, and history of abdominal surgery); 2) preoperative tumor factors (including International Federation of Gynecology and Obstetrics stage and tumor histology); or 3) postoperative pathological factors (including depth of stromal invasion, lymphovascular space invasion, parametrial involvement, lymph node metastasis, and resection margin involvement). Compared with the laparoscopic radical hysterectomy group, more patients in the open radical hysterectomy group had a preoperative squamous cell carcinoma antigen level of greater than 2.5 ng/mL, although the mean preoperative squamous cell carcinoma antigen level did not differ between the two groups. The mean tumor size was significantly larger in the open radical hysterectomy group (2.2 cm compared with 2.8 cm, P=.021), although the difference in mean tumor size between groups (0.6 cm) was small. The proportion of patients with a bulky tumor (greater than 4 cm) did not differ significantly between groups (5.6% compared with 14.3%, P=.098).
Table 2 shows the surgical outcomes in the cohort. No between-group difference was observed for operating time, preoperative and postoperative hemoglobin concentrations, perioperative hemoglobin level change, transfusion requirement, or transfusion volume. Estimated blood loss was statistically lower in the laparoscopic radical hysterectomy group (494 mL compared with 620 mL, P=.009). The time interval to return of bowel movements and duration of postoperative hospital stay were both significantly shorter in the laparoscopic radical hysterectomy group. No between-group difference was observed for the mean total number of retrieved lymph nodes, the number of retrieved para-aortic lymph nodes, or the number of retrieved pelvic lymph nodes.
Table 3 shows all perioperative complications reported in the cohort. No between-group difference was observed for intraoperative complication rate (1.9% compared with 0.9%, P=.546). However, the postoperative complication rate was significantly lower in the laparoscopic radical hysterectomy group (5.6% compared with 17.9%, P=.032). The occurrence of bladder dysfunction did not differ between groups (18.5% compared with 17.9%, P=.917). When we divided the study period into two separate time periods (1998–2005 and 2006–2011), we found that laparoscopic radical hysterectomy was associated with lower estimated blood loss, faster recovery of bowel movement, a shorter postoperative hospital stay, and a reduction in the frequency of postoperative complications during both study periods.
Postsurgery, 20 patients (37%) in the laparoscopic radical hysterectomy group and 45 patients (40.2%) in the open radical hysterectomy group received adjuvant therapy (P=.698). In the laparoscopic radical hysterectomy group, chemotherapy, radiation therapy, and concurrent chemoradiation therapy were used as an adjuvant therapy in a total of four (7.4%), five (9.2%), and 11 patients (20.4%), respectively. In the open radical hysterectomy group, chemotherapy, radiation therapy, and concurrent chemoradiation therapy were used as an adjuvant therapy in a total of 15 (13.4%), 10 (8.9%), and 20 patients (17.9%), respectively. No between-group difference in the type of adjuvant therapy was observed (P=.723). The adjuvant chemotherapy regimen was paclitaxel and cisplatin in nine patients, paclitaxel and carboplatin in five patients, and 5-fluorouracil and cisplatin in five patients. The concurrent chemoradiation therapy regimen was weekly cisplatin in 23 patients, 5-fluorouracil and cisplatin in five patients, and paclitaxel and carboplatin in three patients.
The mean and median follow-up periods in the total cohort were 57.1 months and 44 months, respectively (range 2–146 months). For the laparoscopic radical hysterectomy group, the mean and median follow-up periods were 49.2 months and 42.5 months (range 6–145 months), respectively; and for the open radical hysterectomy group, the mean and median follow-up periods were 60.9 months and 45 months (range 2–146 months), respectively (P=.072). Five patients (9.3%) in the laparoscopic radical hysterectomy group and 15 patients (13.4%) in the open radical hysterectomy group experienced tumor recurrence (P=.443). Disease-related death occurred in one patient (1.9%) in the laparoscopic radical hysterectomy group and nine patients (8%) in the open radical hysterectomy group (P=.169). The 5-year disease-free survival was 88% for the laparoscopic radical hysterectomy group and 85% for the open radical hysterectomy group (P=.682), and the 5-year overall survival was 97% for the laparoscopic radical hysterectomy group and 90% for the open radical hysterectomy group (P=.220) (Fig. 1). In the univariable analysis, International Federation of Gynecology and Obstetrics stage II, a preoperative squamous cell carcinoma antigen level greater than 2.5 ng/mL, tumor size greater than 4 cm, stromal invasion greater than two thirds, lymph node metastasis, parametrial involvement, and requirement for adjuvant therapy were significantly associated with poorer disease-free survival. In the multivariable analysis, International Federation of Gynecology and Obstetrics stage II, tumor size greater than 4 cm, stromal invasion greater than two thirds, and lymph node metastasis were significantly associated with poorer disease-free survival (Table 4). In the univariable analysis, preoperative squamous cell carcinoma antigen level greater than 2.5 ng/mL, tumor size greater than 4 cm, lymphovascular space invasion, lymph node metastasis, parametrial invasion, and requirement for adjuvant therapy were significantly associated with poorer overall survival. In the multivariable analysis, only lymph node metastasis was significantly associated with poorer overall survival (Table 4). After adjustment for significant factors for disease-free survival and overall survival from the univariable analysis, the risk of recurrence (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.33–2.93, P=.982) and death (OR 3.43, 95% CI 0.38–31.13, P=.273) did not differ between groups.
Although laparoscopic radical hysterectomy and open radical hysterectomy were both feasible in the present cohort of obese women with early cervical cancer, laparoscopic radical hysterectomy was associated with superior surgical outcomes in terms of estimated blood loss, time to recovery of bowel movements, duration of postoperative hospital stay, and incidence of postoperative complications. No between-group differences were observed for the risk of postoperative recurrence or death.
Obese women are often considered poor candidates for radical surgery because they frequently have comorbid medical disease, like in the present cohort, as well as increased surgical morbidity and wound complications.9,10 However, previous studies comparing surgical outcomes of open radical hysterectomy in normal-weight and obese women report no difference in terms of operating times, transfusion rates, duration of postoperative stay, incidence of postoperative complications, or long-term complications,11–14 although some studies report increased estimated blood loss in obese women.12,13 Many surgeons are of the opinion that obesity may limit the radicality of surgical resection by reducing the resection of the parametrium and vagina and the number of lymph nodes retrieved and may thus compromise survival. However, previous studies show no difference in the risk of postoperative recurrence or death between normal-weight and obese women after open radical hysterectomy.11–14 Furthermore, one study reports no difference in terms of the extent of the resection of the parametrium and vagina, the rate of negative margins, or the number of pelvic lymph nodes retrieved.24 In the present cohort, open radical hysterectomy was feasible in all consecutive obese women with early-stage cervical cancer. The rate of negative margin resection was as high as 98.2%. Survival outcomes and surgical outcomes, including operating time, estimated blood loss, transfusion requirement, intraoperative and postoperative complications, and the number of lymph nodes retrieved, were similar or even superior to those reported in previous studies of open radical hysterectomy in this population.11,24 We therefore suggest that obesity is not a contraindication to open radical hysterectomy in patients with early-stage cervical cancer.
Currently, laparoscopic radical hysterectomy is considered a reasonable, or even superior, surgical treatment for early-stage cervical cancer. Many previous studies report that laparoscopic radical hysterectomy was associated with superior surgical outcomes compared with open radical hysterectomy, including less blood loss, lower transfusion requirements, more rapid recovery, and a shorter postoperative hospital stay, without increasing postoperative morbidity and without decreasing survival of patients.15–22 However, most of these studies investigated normal-weight women.15–22 Therefore, the present study compares the outcomes of laparoscopic radical hysterectomy and open radical hysterectomy (Piever-Rutledge type 3 hysterectomy) in obese women with early-stage cervical cancer. Laparoscopic radical hysterectomy was as feasible as open radical hysterectomy in obese women, and margin-negative resection was feasible in 98.1% of all obese women undergoing laparoscopic radical hysterectomy. However, laparoscopic radical hysterectomy had more favorable surgical outcomes in terms of estimated blood loss, time to return of bowel movement, duration of postoperative hospital stay, and rate of postoperative complications. In particular, wound complications, deep vein thrombosis, and acute renal failure were less frequent in the laparoscopic radical hysterectomy group. No between-group difference was observed in the risk of recurrence or death. Therefore, we consider laparoscopic radical hysterectomy preferable to open radical hysterectomy in the surgical management of obese patients with early-stage cervical cancer.
The present study had two important limitations. The first was its retrospective design. Second, the selection of laparoscopic radical hysterectomy or open radical hysterectomy was not randomized, and thus potential bias may have been introduced. However, the effect of bias on outcomes probably was minimal because those important clinicopathological factors with a potential influence on surgical and survival outcomes did not differ significantly between the study groups. An important strength of the study was its relatively large sample size.
In our study, 23 patients (42.6%) in the laparoscopic radical hysterectomy group and 73 patients (65.2%) in the open radical hysterectomy group underwent para-aortic lymph node sampling or dissection. Because this was a retrospective study, we are not sure why these procedures were performed more frequently in the open radical hysterectomy group. In the past, even patients with small tumors underwent routine para-aortic lymph node sampling during radical hysterectomy in our center. However, at present we do not perform para-aortic lymph node sampling in patients with tumors less than 4 cm and without pelvic lymph node metastasis because the incidence of para-aortic lymph node metastasis is very low in these patients. If pelvic lymph node metastasis was identified in frozen biopsies during surgery, para-aortic lymph node dissection would be performed.
In our study, the rate of conversion to laparotomy for laparoscopic radical hysterectomy was very low compared with the published conversion rates for simple laparoscopic hysterectomy with pelvic and para-aortic lymphadenectomy for endometrial cancer, which is typically in the range of 5–25%. We think that the very low rate of conversion to laparotomy in our center is the result of the fact that all surgery was performed by experienced laparoscopic oncologic surgeons. A Gynecologic Oncology Group's randomized controlled trial, which was recently published in the literature (Gynecologic Oncology Group LAP2 study), showed that the conversion rate was approximately 25.8% for laparoscopic simple hysterectomy with pelvic and para-aortic lymphadenectomy.25 The main reason for conversion to laparotomy was obesity (in approximately 60% of cases). We think that this was because most laparoscopic surgery was performed by less experienced surgeons who were still gaining experience of laparoscopic oncologic surgery. During the LAP2 trial in the United States (1996–2005), only 8% of surgical staging of uterine cancer was performed laparoscopically.26 In studies of experienced laparoscopic surgeons, who perform laparoscopic staging in consecutive cases with endometrial cancer, the conversion rate was only 3–5%,26,27 and only 7% in patients with a BMI greater than 40.26
In our study, the length of postoperative hospital stay was longer than that observed in Western countries. We believe that our discharge criteria are similar to those in Western countries because we recommended discharge when the patient can eat, void, and defecate properly and shows no evidence of postoperative complications. However, Korean patients with cancer have comprehensive insurance coverage and hospital charges are very low in Korea. Therefore, most Korean patients who undergo surgery prefer to remain in the hospital for a considerable period of time, despite our advice regarding earlier discharge. In short, the relatively long postoperative hospital stay observed for the patients in our study is common in the Korean medical environment and is not specific to our hospital or our study. Nevertheless, the length of the hospital stay for patients undergoing laparoscopic radical hysterectomy was significantly shorter than that for patients undergoing open radical hysterectomy.
In conclusion, laparoscopic radical hysterectomy and open radical hysterectomy were both feasible in the present cohort of obese patients with early-stage cervical cancer. However, laparoscopic radical hysterectomy was associated with more favorable surgical outcomes, including a decrease in estimated blood loss, more rapid recovery of bowel movement, shorter postoperative hospital stay, and fewer postoperative complications, without compromising survival outcomes.
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© 2012 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
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