Operative laparoscopy has long been a mainstay in the treatment of benign gynecologic conditions. In fact, gynecologists developed the laparoscope as a diagnostic tool in the 1960s and pioneered its use in minimally invasive surgery in the 1970s when they began using the technology to perform tubal ligations.1 Gynecologic oncologists were initially slow to adopt laparoscopic techniques, initially using the approach for prophylactic bilateral salpingo-oophorectomy for high-risk women and for second-look evaluations for patients with a history of ovarian cancer.2
In the 1990s gynecologic oncologists began to use laparoscopy to perform hysterectomies and lymph node dissections in women with endometrial cancer. They did not observe an increase in complication rates,3 but they did find a decrease in postoperative length of hospital stay, which was associated with lower cost of treatment.3,4 In addition, the minimally invasive approach improved patient quality of life by allowing women to return to baseline functioning sooner.5 These retrospective studies were eventually validated prospectively by a Gynecologic Oncology Group Study (LAP-2) that confirmed that the laparoscopic approach was comparable to open surgery with equivalent surgical outcomes and complications and that there was no difference in long-term quality of life resulting from these techniques; however, the laparoscopic approach was associated with decreased hospital length of stay, improved short-term quality of life, and earlier return to baseline functioning (Walker JL, Piedmonte M, Spirtos N, Eisenkop S, Schlaerth J, Mannel RS, et al. Surgical staging of uterine cancer: randomized phase III trial of laparoscopy compared with laparotomy—A Gynecologic Oncology Group Study [GOG]: preliminary results [abstract]. Proceedings of the 2006 Annual Meeting of the American Society of Clinical Oncology, June 2–6, 2006, Atlanta, Georgia).
Total laparoscopic radical hysterectomy (TLRH) for the treatment of patients with cervical cancer was also first described in the early 1990s.6,7 However, unlike in the case of endometrial cancer, only recently have authors begun to publish their experiences with this approach,8–11 likely because recent advances in laparoscopic techniques and equipment have made TLRH feasible and safe. In 2004, we began to offer TLRH with pelvic lymphadenectomy to patients with early-stage cervical cancer. Today, some of our surgeons prefer to perform radical hysterectomies laparoscopically, whereas others continue to approach the procedure through a laparotomy incision.
We therefore had the unique opportunity to evaluate two different surgical approaches at a single institution over the same period of time instead of comparing to historical controls. The objective of this study was to compare intraoperative, pathologic, and postoperative outcomes of TLRH with abdominal radical hysterectomy (ARH) and pelvic lymphadenectomy for women with early-stage cervical cancer.
PARTICIPANTS AND METHODS
Before initiation, our retrospective study was approved by the M. D. Anderson Institutional Review Board. We reviewed the records of all patients who underwent either TLRH or ARH and pelvic lymphadenectomy for cervical cancer at The University of Texas M. D. Anderson Cancer Center from January 1, 2004, through December 31, 2006. We included all patients with stages IA1–IB2 primary cervical cancer with either squamous, adenocarcinoma, or adenosquamous lesions who underwent a type III (Meigs) radical hysterectomy. Patients were excluded if they had nonsquamous or nonadenocarcinoma histologies, such as melanoma, clear-cell, or neuroendocrine tumors; if they had undergone radical hysterectomy for clinical stage II endometrial cancer; if they had undergone a type II (Wertheim or “modified”) radical hysterectomy; or if they were explored for radical hysterectomy but had the procedure aborted due to intraperitoneal disease or nodal involvement.
At our institution, new patients are typically assigned to clinicians randomly based on which surgeon is available for a new patient work-up. It is then the surgeon’s and the patient’s decision as to which patients receive the open compared with the laparoscopic approach. However, certain individual surgeons within the division are more likely to perform open radical hysterectomy while others will usually favor the laparoscopic approach. In addition, a number of patients specifically come to our institution self-referred requesting a laparoscopic approach to the radical hysterectomy.
For the ARH approach, a type III (Meigs) radical hysterectomy was performed. Total laparoscopic radical hysterectomy and pelvic lymphadenectomy were performed in the manner previously described.12 Pelvic lymphadenectomy, with or without lymphatic mapping, was typically performed after completion of the radical hysterectomy. Estimated blood loss was determined by the anesthesiologist and recorded accordingly. Typically, the surgeon would submit to this estimate unless he or she feels strongly that the anesthesiologist may have grossly overestimated (eg, patients with ascites mixed with blood) or underestimated blood loss (eg, patients where large amounts of blood were evacuated using towels or laparotomy pads).
After TLRH, we typically discharge patients from the hospital with a Foley or suprapubic catheter and prophylactic antibiotics. Because of the large number of surgeons performing open radical hysterectomies at our institution, practice patterns regarding bladder management varied, with some patients being sent home with Foley catheters or suprapubic catheters and others with instructions for intermittent self-catheterization. Most patients are discharged with prophylactic antibiotics until the catheter is removed, and all patients are scheduled to return to the clinic approximately 2 weeks postoperatively for a voiding trial. An adequate voiding trial is usually defined as a residual volume of urine less than 100 mL. Patients who fail the voiding trial have the catheter replaced for further bladder rest, and follow-up voiding trials are scheduled at the clinician’s discretion.
All pathologic specimens were examined by an attending pathologist. Before pathologic processing, radical hysterectomy specimens were grossly examined. At the time of gross inspection, the size of parametrium was measured linearly from its attachment to the cervix. The size of the vaginal cuff obtained was also measured in a similar manner.
The Shapiro-Wilk test for normality was applied to all comparison groups. Parametric continuous variables were compared using Student t test for independent samples. Nonparametric continuous and dichotomous variable comparisons were performed using the Mann-Whitney U test and the χ2 test, respectively. Mean values are reported throughout the manuscript unless otherwise noted. Two-tailed P values were reported. A P value of less than .05 was considered to indicate statistical significance. For all statistical analyses SPSS 13 for Windows (SPSS Inc., Chicago, IL) was used.
A total of 89 women met our inclusion criteria. Abdominal radical hysterectomy was performed in 54 patients, and TLRH was performed in 35 women. The mean age for the entire cohort was 41.8 years (range, 27–68 years), and the mean body mass index (BMI) was 28.1 kg/m2 (range, 17.4–46.4 kg/m2). Other patient demographics are detailed in Table 1. The patient groups were similar with respect to age, weight, BMI, and ethnicity. In addition, there were no differences among the groups with respect to tumor factors such as clinical stage, histology, or preoperative depth of invasion.
Patients who underwent ARH had a mean blood loss of 548 mL compared with 319 mL for those who had TLRH (P=.009). In addition, 15% of patients undergoing ARH and 11% of those undergoing TLRH required intraoperative or postoperative transfusion (P=.62). Operative times were significantly longer for TLRH than for ARH (344 minutes compared with 307 minutes, respectively; P=.03). Intraoperative complications for the two cohorts are listed in Table 2.
Two patients (5.7%) in the TLRH group required conversion to laparotomy to manage vascular injuries. The first patient had a trocar injury to the left external iliac vein at the start of the procedure. The second patient had an injury to the right external iliac vein that occurred during the pelvic lymphadenectomy after the TLRH had been completed. A third patient had an injury to the inferior epigastric vessels that tamponaded with the trocar and was then easily repaired at the end of the procedure after removal of the trocar. One patient in each group had an inadvertent cystotomy that, for the patient undergoing TLRH, was repaired laparoscopically.
Patients who underwent TLRH had a significantly shorter length of hospital stay than those who underwent ARH (median length of stay 2.0 days compared with 5.0 days, respectively; P<.001). In addition, 53% of the patients who underwent ARH compared with only 18% who underwent TLRH had some form of postoperative infectious morbidity (P=.001). Details of postoperative morbidity are given in Table 3. There was no difference in overall noninfectious postoperative morbidity between the two groups (P=.62). There was no difference in time to return of voiding function (median 13 days [range 3–40 days] for ARH compared with 13.5 days [range 8–26 days] for TLRH, P=.26). At 14 days postoperatively, 69% of the ARH cohort and 55% of the TLRH group had attained normal voiding function (P=.29) and by 21 days 87% of the ARH cohort and 82% of the TLRH group had attained normal voiding function (P=.60). None of the 89 patients had any long-term bladder atony.
There was no statistically significant difference in readmission rates for the two groups (P=.80). Seven percent (four patients) of those who underwent ARH were readmitted: one for fever of unknown origin, one for wound cellulitis requiring administration of intravenous antibiotics, one for pelvic abscess, and one for pulmonary embolus. Nine percent (three patients) of those who underwent TLRH were readmitted: one for fever of unknown origin, one for pyelonephritis, and one for pulmonary embolus.
The median duration of follow-up for all patients was 13.0 months (15.2 months for ARH and 7.2 months for TLRH). At the time of this report, three patients had experienced disease recurrence. The first patient underwent ARH for a stage IB1, poorly differentiated squamous cell carcinoma of the cervix. Postoperative pathology was positive for a single lymph node with microscopic metastasis. The patient received postoperative chemoradiation but was noted to experience recurrence in the pelvis 14 months after completion of adjuvant therapy. She was alive with disease and receiving palliative chemotherapy. The second patient had a stage IB1 moderately differentiated adenocarcinoma of the cervix and underwent ARH. Final pathology revealed negative margins and lymph nodes. She experienced recurrence at the vaginal cuff 6 months postoperatively and at the time of this report was alive without evidence of disease after salvage chemoradiation. The third patient underwent TLRH for a stage IB1 poorly differentiated squamous cell carcinoma of the cervix. Results from final pathology examinations demonstrated negative margins and negative lymph nodes. She was noted to have a central recurrence three months after surgery and was undergoing salvage chemoradiation. Due to the short follow-up period, data for progression-free and overall survivals have yet to mature.
The final pathologic findings are described in Table 4. There were no differences between the two groups with respect to the amount of parametrium or vaginal cuff resected or the number of patients with negative margins. There was also no statistically significant difference in the number of patients in the ARH and the TLRH groups who had lymph node metastasis (26% compared with 14%, respectively, P=.19). The total number of pelvic lymph nodes resected was significantly higher with ARH than with TLRH (18.7 compared with 13.5, respectively; P=.001). Interestingly, when evaluated by side, there was a significant difference in number of right pelvic nodes resected (9.6 for ARH compared with 6.3 for TLRH, P<.001) but no significant difference in the number of left pelvic nodes resected (9.1 for open compared with 7.2, respectively, P=.06).
Despite longer operative time, we found that patients with early-stage cervical cancer who underwent TLRH experienced decreased blood loss and shorter hospital stays than those who underwent ARH. In addition, there was significantly less postoperative febrile morbidity for those patients who underwent TLRH, and there were no differences in postoperative noninfectious morbidities between the two groups. Pathologic specimens were equivalent for the two groups with respect to amount of parametrial and vaginal tissue obtained.
Few studies have compared TLRH to ARH. Li et al13 recently published their comparison of 90 laparoscopic and 35 open radical hysterectomies and pelvic lymphadenectomies. Similar to our study, they found increased operative time in the group that underwent TLRH and no difference in intraoperative complications or time to return of urinary function. They also reported earlier return of bowel function in the TLRH group. We did not include this end point in the present study given the inaccuracies that can occur when retrospectively assessing this variable. Interestingly, Li et al found no difference in blood loss (370 mL for TLRH compared with 455 mL for ARH) nor in length of hospital stay between the two groups (13.81 days for TLRH compared with 13.69 days for ARH). The two study groups were heterogenous however, as the ARH group had significantly more patients with advanced-stage disease and nonsquamous histologic subtypes than the TLRH group, making direct comparisons potentially hazardous. The long length of hospital stay and the willingness of the practitioners to perform surgery on locally advanced cervical cancer clearly reflect regional practice patterns, making it difficult to apply their findings to our patient population.
Our findings of decreased blood loss and length of hospital stay are consistent with other reports in the literature for TLRH10 and laparoscopic-assisted vaginal radical hysterectomies.14 However, unlike previous reports, our study did not identify any significant difference in the number of patients who required intraoperative or postoperative transfusion. Interestingly, our transfusion rate of 15% for patients who underwent ARH is much lower than the 49–81% previously reported for patients undergoing ARH.15–20 This finding may be attributable to our criteria for selection of candidates for surgery. We typically perform radical hysterectomies only for patients with lesions less than 4 cm in size that are confined to the cervix (stage IB1 or smaller). Only one patient in this study had a stage IB2 tumor, and no patients had lesions extending beyond the cervix (stage II or larger). Other surgeons may routinely perform radical hysterectomy on larger lesions, which may account for some added blood loss. Another factor that may explain our decreased blood loss compared with other institutions may be the application of laparoscopic technology to open surgeries. We have adapted many of the instruments developed for laparoscopy, such as the Harmonic ACE (Ethicon Endo-Surgery, Inc., Cincinnati, OH) and the LigaSure (ValleyLab, Boulder, CO), to surgeries performed by laparotomy and are experiencing less blood loss and faster operating times for vulvar, cervical, uterine, and ovarian cancers. We recently published our experience in applying these technologies to pelvic exenterative procedures and similarly found less blood loss, fewer transfusions, and decreased length of hospital length of stay.21
Our average operative time of 344 minutes for TLRH and pelvic lymphadenectomy may discourage some surgeons from undertaking the procedure. Many published reports, nonetheless, describe operative times of less than 271 minutes.22–24 Two factors may explain our longer operative times. First, as with any new technique, there is a learning curve. Spirtos et al24 published their experience performing 78 TLRHs and reported an overall operative time of 205 minutes. The operative time for the first 26 patients averaged 255 minutes, whereas in the last 52 patients, the procedures were completed within 186 minutes. Similar learning curves have been reported in laparoscopic hysterectomy and lymph node staging in patients with endometrial cancer.25,26 To date we have successfully completed 35 TLRHs; however, this experience is spread out among several surgeons, some of whom may still be at the early part of the learning curve.
The second factor contributing to our longer operative time is likely our institution’s graduate medical training program. Our gynecologic oncology fellows and obstetrics and gynecology residents routinely participate in all of the gynecologic oncology surgeries. Our average operative times of 307 minutes for ARH and 344 minutes for TLRH are similar to those reported by Memorial Sloan Kettering Cancer Center (296 minutes and 371 minutes, respectively), another institution that involves trainees in surgeries.10
Although long-term survival data have yet to mature, our data suggest that TLRH is comparable to ARH with respect to the adequacy of the radical surgical resection. We found no difference in pathologic specimens with respect to the amount of parametrial tissue resected or vaginal cuff obtained. In addition, there was no difference in positive margins of surgical specimens between the two groups. Although there was a statistically significant difference in the number of nodes removed by total and right pelvic lymph node dissections (with no difference in number of left pelvic lymph nodes removed), the clinical significance of this small discrepancy is likely minimal. In Gynecologic Oncology Group Study LAP-2 (Walker et al [abstract]), the large, prospective, randomized study of laparoscopy for endometrial cancer, it was noted that patients in the open group had more para-aortic lymph nodes resected than those in the laparoscopy group; however, there was no difference in the number of patients with positive para-aortic lymph nodes, suggesting that the absolute number of lymph nodes resected may not be a reliable factor.
The limitations of this study are those common to all retrospective studies. In particular, some might argue a large degree of selection bias may confound the results reported here within. As mentioned, however, although individual surgeons in our division are more likely to perform laparoscopic or open radical hysterectomy based on training and comfort, the patients are randomly assigned to physicians within our group depending on physician availability at time of the new referral into our institution. As Table 1 shows, there was no difference in the two patient cohorts with respect to preoperative demographic, physical, or tumor factors. Therefore, selection bias may play a very limited role in this analysis.
Total laparoscopic radical hysterectomy, although technically difficult to perform, is a feasible and safe procedure that has fewer intraoperative and postoperative morbidities than ARH and long-term outcomes that are likely equivalent to the those of ARH. As laparoscopic technology and equipment improve and as surgeons become more comfortable with minimally invasive techniques, we believe TLRH will be performed more commonly. In addition, robotic surgery will allow for additional comfort and facility in performing the surgery. In fact, reports of robotically-assisted laparoscopic radical hysterectomy are already emerging.27 We are planning to prospectively validate the findings of the current study with a multi-institutional, international, randomized trial involving gynecologic oncology members of the American Association of Gynecologic Laparoscopists.
1.Gordon AG, Magos AL. The development of laparoscopic surgery. Baillieres Clin Obstet Gynaecol 1989;3:429–49.
2.Husain A, Chi DS, Prasad M, Abu-Rustum N, Barakat RR, Brown CL, et al. The role of laparoscopy in second-look evaluations for ovarian cancer. Gynecol Oncol 2001;80:44–7.
3.Gemignani ML, Curtin JP, Zelmanovich J, Patel DA, Venkatraman E, Barakat RR. Laparoscopic-assisted vaginal hysterectomy for endometrial cancer: clinical outcomes and hospital charges. Gynecol Oncol 1999;73:5–11.
4.Scribner DR Jr, Mannel RS, Walker JL, Johnson GA. Cost analysis of laparoscopy versus laparotomy for early endometrial cancer. Gynecol Oncol 1999;75:460–3.
5.Spirtos NM, Schlaerth JB, Gross GM, Spirtos TW, Schlaerth AC, Ballon SC. Cost and quality-of-life analyses of surgery for early endometrial cancer: laparotomy versus laparoscopy. Am J Obstet Gynecol 1996;174:1795–9. Available at:.
6.Canis M, Mage G, Wattiez A, Pouly JL, Manhes H, Bruhat MA. Does endoscopic surgery have a role in radical surgery of cancer of the cervix uteri [in French]? J Gynecol Obstet Biol Reprod (Paris) 1990;19:921.
7.Nezhat CR, Burrell MO, Nezhat FR, Benigno BB, Welander CE. Laparoscopic radical hysterectomy with paraaortic and pelvic node dissection. Am J Obstet Gynecol 1992;166:864–5.
8.Ramirez PT, Slomovitz BM, Soliman PT, Coleman RL, Levenback C. Total laparoscopic radical hysterectomy and lymphadenectomy: the M. D. Anderson Cancer Center experience. Gynecol Oncol 2006;102:252–5.
9.Nezhat F, Mahdavi A, Nagarsheth NP. Total laparoscopic radical hysterectomy and pelvic lymphadenectomy using harmonic shears. J Minim Invasive Gynecol 2006;13:20–5.
10.Abu-Rustum NR, Gemignani ML, Moore K, Sonoda Y, Venkatraman E, Brown C, et al. Total laparoscopic radical hysterectomy with pelvic lymphadenectomy using the argon-beam coagulator: pilot data and comparison to laparotomy [published erratum appears in Gynecol Oncol 2004;93:275]. Gynecol Oncol 2003;91:402–9.
11.Gil-Moreno A, Puig O, Perez-Benavente MA, Diaz B, Verges R, De la Torre J, et al. Total laparoscopic radical hysterectomy (type II-III) with pelvic lymphadenectomy in early invasive cervical cancer. J Minim Invasive Gynecol 2005;12:113–20.
12.Frumovitz M, Ramirez PT. Total laparoscopic radical hysterectomy: Surgical technique and instrumentation. Gynecol Oncol 2007;104 suppl:13–6.
13.Li G, Yan X, Shang H, Wang G, Chen L, Han Y. A comparison of laparoscopic radical hysterectomy and pelvic lymphadenectomy and laparotomy in the treatment of Ib-IIa cervical cancer. Gynecol Oncol 2007;105:176–80.
14.Steed H, Rosen B, Murphy J, Laframboise S, De Petrillo D, Covens A. A comparison of laparoscopic-assisted radical vaginal hysterectomy and radical abdominal hysterectomy in the treatment of cervical cancer. Gynecol Oncol 2004;93:588–93.
15.Eisenkop SM, Spirtos NM, Montag TW, Moossazadeh J, Warren P, Hendrickson M. The clinical significance of blood transfusion at the time of radical hysterectomy. Obstet Gynecol 1990;76:110–3.
16.Morris PC, Haugen J, Tomjack J, Anderson B, Buller RE. Blood transfusion and the risk of recurrence in stage IB cervical cancer. Gynecol Oncol 1995;57:401–6.
17.Monk BJ, Tewari K, Gamboa-Vujicic G, Burger RA, Manetta A, Berman ML. Does perioperative blood transfusion affect survival in patients with cervical cancer treated with radical hysterectomy? Obstet Gynecol 1995;85:343–8.
18.Azuma C, Koyama M, Inagaki M, Ito S, Sawada M, Saji F, et al. The influence of peri-operative blood transfusion during radical hysterectomy on the prognosis of uterine cervical cancer. Transfus Sci 1997;18:55–62.
19.Lentz SS, Shelton BJ, Toy NJ. Effects of perioperative blood transfusion on prognosis in early-stage cervical cancer. Ann Surg Oncol 1998;5:216–9.
20.Spirtos NM, Westby CM, Averette HE, Soper JT. Blood transfusion and the risk of recurrence in squamous cell carcinoma of the cervix: a gynecologic oncology group study. Am J Clin Oncol 2002;25:398–403.
21.Slomovitz BM, Ramirez PT, Frumovitz M, Soliman PT, Bevers M, Coleman RL, et al. Electrothermal bipolar coagulation for pelvic exenterations. Gynecol Oncol 2006;102:534–6.
22.Gil-Moreno A, Diaz-Feijoo B, Roca I, Puig O, Perez-Benavente MA, Aguilar I, et al. Total laparoscopic radical hysterectomy with intraoperative sentinel node identification in patients with early invasive cervical cancer. Gynecol Oncol 2005;96:187–93.
23.Pomel C, Atallah D, Le Bouedec G, Rouzier R, Morice P, Castaigne D, et al. Laparoscopic radical hysterectomy for invasive cervical cancer: 8-year experience of a pilot study. Gynecol Oncol 2003;91:534–9.
24.Spirtos NM, Eisenkop SM, Schlaerth JB, Ballon SC. Laparoscopic radical hysterectomy (type III) with aortic and pelvic lymphadenectomy in patients with stage I cervical cancer: surgical morbidity and intermediate follow-up. Am J Obstet Gynecol 2002;187:340–8.
25.Eltabbakh GH. Effect of surgeon’s experience on the surgical outcome of laparoscopic surgery for women with endometrial cancer. Gynecol Oncol 2000;78:58–61.
26.Holub Z, Jabor A, Bartos P, Hendl J, Urbanek S. Laparoscopic surgery in women with endometrial cancer: the learning curve. Eur J Obstet Gynecol Reprod Biol 2003;107:195–200.
27.Sert BM, Abeler VM. Robotic-assisted laparoscopic radical hysterectomy (Piver type III) with pelvic node dissection—case report. Eur J Gynaecol Oncol 2006;27:531–3.