Pretreatment Transperitoneal Laparoscopic Staging Pelvic and Paraaortic Lymphadenectomy in Large (≥5 cm) Stage IB2 Cervical Carcinoma: Report of a Pilot Study

GYNECOLOGIC ONCOLOGY ARTICLE NO.

63, 333–336 (1996)

0332

Pretreatment Transperitoneal Laparoscopic Staging Pelvic and Paraaortic Lymphadenectomy in Large (§5 cm) Stage IB2 Cervical Carcinoma: Report of a Pilot Study FERNANDO O. RECIO, M.D., M. STEVEN PIVER, M.D.,

AND

RONALD E. HEMPLING, M.D.

Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263 Received April 2, 1996

Twelve patients with large stage IB2 (5–8 cm) cervical carcinoma underwent transperitoneal laparoscopically directed pelvic and paraaortic lymph node dissection prior to the initiation of radiation therapy. The mean length of operation was 176 min and the mean estimated blood loss was 60 cc. An average of 25 lymph nodes were retrieved from each patient: 18 pelvic lymph nodes and 7 paraaortic lymph nodes. No patients were hospitalized for more than 24 hr. No operative complications were observed. Pelvic nodal metastases were diagnosed in three patients, all of whom had negative computerized tomography (CT) scans prior to surgery. All patients began radiation therapy within 1 week of surgery. Laparoscopically directed lymphadenectomy for patients with stage IB2 cervical carcinoma is technically feasible, is associated with minimal morbidity, short hospital stay, and minimal delay prior to radiation therapy, and can add valuable information to radiation treatment planning. q 1996 Academic Press, Inc.

INTRODUCTION

Survival of patients with stage IB cervical cancer measuring greater than 3 cm treated by type III hysterectomy and pelvic lymphadenectomy is significantly lower than that of patients with cervical cancer £3 cm similarly treated [1]. Because of this difference in prognosis, the International Federation of Gynecologists and Obstetricians (FIGO) has recently designated cervical lesions £4 cm as stage IB1 and lesions greater than 4 cm in size as clinical stage IB2 [2]. While surgical staging among patients with cervix cancer remains controversial, a growing body of evidence has accumulated which indicates that information gained from such staging procedures may prove useful in treatment planning. Authoritative studies have demonstrated that there is a discrepancy in the estimation of extent of disease which approximates 20–40% when clinically staged and surgically staged patients are compared [3–6]. Moreover, since the 1970s, seminal studies by Rutledge and co-workers [7], Nelson et al. [8], and Piver et al. [9], among others, have demonstrated that 6–33% of patients with cervix cancer will have metastases to the paraaortic lymph nodes. Such metastases lie out-

side standard treatment fields for patients with cervix cancer and cannot be reliably detected by currently available imaging studies. Intriguing, as well, are recently reported data by Potish and co-workers [10] and Downey et al. [11] which indicate that the resection of lymph node metastases among patients with cervix cancer may have a salutory effect on survival. Because surgical staging operations have been associated with prolonged hospitalization, delay in the initiation of radiation therapy, and treatment-related morbidity, their wide acceptance has not been forthcoming. More recently, studies have demonstrated that laparoscopically directed resection of pelvic and paraaortic lymph nodes in patients with cervical carcinoma is feasible [12–14]. Moreover, the risk for complications from such operations is low and the time spent in the hospital is short. Encouraged by these reports, we initiated a pilot study to evaluate laparoscopically directed surgical staging among patients with large (5–8 cm) stage IB2 cervical carcinoma. MATERIALS AND METHODS

Between March 1995 and March 1996, 12 consecutive patients with FIGO stage IB2 invasive cervical cancer underwent laparoscopic transperitoneal pelvic and paraaortic lymphadenectomy prior to the initiation of definitive radiation therapy. Patient characteristics are outlined in Table 1. All patients underwent a complete history and physical examination, complete blood count, chemistry profile, evaluation of coagulation parameters, electrocardiogram, chest X ray, and computerized tomographic (CT) evaluation of the abdomen and pelvis. Preoperative bowel preparation consisted of a clear liquid diet for 2 days prior to surgery and 240 cc of magnesium citrate on the evening prior to operation. Sequential compression devices and subcutaneous heparin were prescribed for all patients as thrombosis prophylaxis. All patients received a single dose of cefoxitin 2 g intravenously on call to the operating room. Following the induction of general endotracheal anesthesia, patients had a nasogastric tube placed.

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0090-8258/96 $18.00 Copyright q 1996 by Academic Press, Inc. All rights of reproduction in any form reserved.

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TABLE 1 Patient Characteristics

Patient No.

Age (years)

Lesion size (cm)

Quetlet index

Operating time (min)

1 2 3 4 5 6 7 8 9 10 11 12 Mean

49 48 31 51 53 45 29 48 42 53 42 31 44

8 8 8 8 7 7 7 8 7 7 5 5 7

25 31 27 39 35 20 23 29 28 22 29 17 27

170 215 145 270 200 155 145 185 165 155 175 135 176

Patients were then placed in the modified lithotomy position with both knees below the level of the iliac crests and the legs supported in Allen stirrups. Shoulder braces were secured in place and the arms were secured to the sides. A team of two surgeons performed the operation. Laparoscopic equipment for all cases consisted of a three-chip camera attached to a 10-mm laparoscope, two video monitors, a high flow CO2 gas insufflator, and a high-pressure suction irrigation apparatus. The peritoneal cavity was entered via a infraumbilical incision employing the technique described by Hasson [15]. A pneumoperitoneum of 4 liters of carbon dioxide was created and intraabdominal pressure did not exceed 15 mm of Hg. The pelvic and abdominal contents were evaluated. In the absence of prohibitive abnormality and under direct visualization, a 10-mm trocar was placed into the peritoneal cavity through a stab incision created in the midline of the abdominal wall approximately 4 cm cephalad to the symphysis pubis. Similarly, under direct visualization, 12-mm trocars were placed 3 cm medial to each anterior iliac crest. In two patients, a fifth incision was made 6 cm cephalad to the infraumbilical incision for the placement of a laparoscopic organ retractor. Metzenbaum scissors with monopolar cautery capability or laparosonic coagulating shears (UltraCision, Inc.) were used to perform the retroperitoneal pelvic and paraaortic lymphadenectomy in six patients each. The patients were placed in a steep Trendelenburg position (20–307) and the small bowel was retracted into the right upper quadrant. The right pelvic lymphadenectomy was performed first. The peritoneum lateral to the obliterated right umbilical ligament was incised and dissected cephalad across the right external iliac artery to the psoas muscle. The right ureter was identified and the paravesical and pararectal spaces were developed. If ovarian function was to be preserved, the uteroovarian ligament at the level of the uterine

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Number of pelvic nodes (positive) 23 17 25 12 16 19 18 22 15 19 17 20 18

(0) (3) (0) (2) (4) (0) (2) (0) (0) (0) (0) (0)

Number of paraaortic nodes (positive) 10 6 7 3 3 10 7 7 6 7 6 7 7

(0) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0)

Estimated blood loss (cc) 55 75 50 85 100 30 75 110 60 40 25 25 60

cornua was divided at this time by creating a window in the posterior leaf of the broad ligament and securing the pedicle with two sutures of 0 Vicryl (Ethicon, Inc.). The pedicle was then divided and an oophoropexy was performed by suturing the pedicle to the ipsilateral mid-paracolic gutter. The lymphoadipose tissue overlying the external, internal, common iliac, and superior vesical arteries was resected with sharp dissection. The external iliac vein was retracted laterally and lymph nodes inferior to it were resected. The obturator nerve was identified and lymphoadipose tissue superior to it was resected. Dissection was carried to the origin of the internal iliac artery. The lymphoadipose tissue specimen was removed through a 12-mm port and enlarged nodes were submitted for frozen section. The procedure was then repeated on the left side of the pelvis. In order to proceed to paraaortic lymphadenectomy, the Trendelenburg position was increased to 40 – 607. The video monitors were moved to the head of the table and the laparoscope was inserted through the suprapubic port. The peritoneal incision which was previously made overlying the right common iliac artery was then extended cephalad superficial to the right ureter, over the aorta, to the level of the third portion of the duodenum. The ureter was retracted laterally. The lymphoadipose tissue overlying the great vessels was elevated and dissected free from underlying structures using laparoscopic/laparosonic coagulating shears. Dissection was initiated in the aortocaval space and carried cephalad to the third portion of the duodenum, lateral to the right ureter, and inferiorly to the mid portion of the right common iliac artery. The lower left paraaortic lymphadenectomy was then performed. The origin of the inferior mesenteric artery (IMA) was identified and the vessel was retracted laterally. The left ureter was identified and retracted laterally. The lymphoadipose tissue overlying this portion of the aorta was then dissected free from the level of the mid portion of the left

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LAPAROSCOPIC STAGING IN STAGE IB2 CERVICAL CANCER

common iliac artery to the origin of the IMA. Enlarged lymph nodes were submitted for frozen section analysis. No drains were employed. Postoperatively, patients were admitted to the hospital for overnight observation. Patients were evaluated by the radiation therapist the day after surgery and simulation accomplished prior to discharge. External beam radiation was initiated 5–7 days after surgery in all patients. RESULTS

Twelve patients with stage IB2 invasive cervical carcinoma underwent laparoscopic transperitoneal bilateral pelvic and lower paraaortic lymphadenectomies prior to initiation of radiation therapy. The mean age of the patient population was 44 years (range 29–53). The mean size of the lesion in this population was 7 cm (range 5–8 cm). Three patients had cervical adenocarcinoma and nine patients had squamous cell carcinoma. The mean Quetelet index [(weight in kg/(height in m)2] of the population was 27 (range 17–39). No enlarged retroperitoneal lymph nodes were identified preoperatively on CT scan of the pelvis and abdomen. Metastasis to pelvic lymph nodes was detected in three patients. Two of these patients had lymph nodes which were appreciably enlarged (2 1 2 cm) at the time of surgery and had not been detected at CT scan. The third patient had microscopically detected metastasis in a clinically apparent normal lymph node. None of the 12 patients had metastasis to the paraaortic nodes. An overall average of 25 lymph nodes were retrieved from each patient (range 15–33). Pelvic lymph node dissection yielded an average of 18 nodes (10 right; 8 left) and paraaortic dissection an average of seven nodes. The mean length of operative procedure was 176 min. The mean estimated blood loss was 60 cc (25–110 cc). No complications attributable to surgery were observed. No patient remained hospitalized for more than 24 hr. All patients initiated radiation therapy within 1 week of surgery. DISCUSSION

Despite several studies which have demonstrated the inaccuracy of clinical staging among patients with cervical carcinoma, this disease remains the only gynecologic malignancy which does not require a surgical procedure to determine the extent of disease prior to classification and initiation of therapy [16]. While a recent change in FIGO classification which stratifies disease confined to the cervix as IB1 if the lesion is less than 4 cm in diameter and IB2 if the lesion is greater than 4 cm in diameter demonstrates a recognition of the variability of lesion size within this stage, it does not acknowledge the significance of lesion size in the surgical/ pathologic spread pattern of the disease and nodal status remains unaddressed as the criterion for staging [2]. Supportive of early studies by Piver and Chung which demonstrated a significant correlation between lesion size in

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patients with stage I cervix cancer and pelvic lymph node metastasis, Delgado and co-workers in a series of two large studies demonstrated a significant risk for nodal metastasis and decreased disease-free survival among patients with lesions measuring greater than or equal to 3 cm in diameter [1, 17, 18]. Moreover, recent studies confirmed the clinical suspicion that there is a correlation between lesion size and paraaortic lymph node metastasis [19, 10]. A recent review of the literature demonstrates the overall incidence of paraaortic lymph node metastasis for patients with stage IB cervix cancer approximates 6% [20]. However, while Delgado et al. demonstrated a virtual absence of paraaortic node metastasis in a group of 18 patients with lesions measuring less than 3 cm in diameter, Potish and co-workers found paraaortic node metastasis in 15% of 54 patients with lesions measuring greater than 3 cm in size [19, 10]. Accordingly, a substantial proportion of patients with large lesions confined to the cervix will have untreated disease if standard pelvic teletherapy is employed. The fact that no patient in the current series was found to have metastasis to the paraaortic nodes is ascribable to the small number of patients who underwent surgery and should not diminish the importance of the aforementioned studies. These findings highlight the importance of evaluating the status of the paraaortic nodes in patients with stage IB2 cervical carcinoma. Since imaging studies have failed to demonstrate the requisite sensitivity and specificity to ensure accurate diagnosis, surgical assessment of the paraaortic nodes in this group of patients seems eminently reasonable [21, 22]. Moreover, recent studies have indicated that resection of involved lymph nodes may offer a significant survival advantage. Downey and co-workers and Potish et al. have reported a significant improvement in 5-year disease-free survival and local regional control rates for patients in whom pelvic or paraaortic nodes grossly enlarged by metastatic cervical carcinoma could be resected prior to the initiation of radiation therapy [10, 11]. In the current series, the mean number of lymph nodes retrieved was 28 and the mean operating time was 176 min. The average hospital stay was 1 day. These data compare favorably with those reported by Childers and coauthors [12]. These authors performed transperitoneal laparoscopically directed pelvic and paraaortic lymph node dissection in a group of 18 patients who subsequently underwent radical hysterectomy. The mean number of nodes retrieved in this study was 31.4 and the operating time ranged from 75 to 175 min. The average hospital stay was 1.5 days. Neither series described a significant intraoperative or postoperative complication. Similarly, Su and co-workers described a group of 38 patients with cervical carcinoma who underwent staging paraaortic lymph node sampling employing laparoscopic techniques [23]. The average duration of the operation was 77 min and the mean number of lymph nodes retrieved was 15. Of interest, patients in this series

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with early-stage disease who subsequently underwent radical hysterectomy and resection of residual lymphoadipose tissue were found to have a mean of less than one residual node. These data indicate that in experienced hands laparoscopically directed procedures can result in an adequate sampling of nodal tissues. While no intraoperative complications are described in the current report, other authors have described at least one caval laceration and one ureteral transection during laparoscopically directed lymphadenectomy [23]. A review of the literature indicates that such injuries are rare and decrease in frequency as experience with the technique is gained [24]. Six patients in the current study underwent surgery performed using electrocoagulation and in six the ultrasonic coagulating shears were employed. While both instruments offer the advantage of obviating the need for endoscopic clip application for hemostasis, the latter instrument offers the additional advantage of minimal plume formation and the maintenance of a clear video projection during operation. Surgery has not as yet been routinely integrated into the staging of patients with cervical carcinoma. However, the recognition that patients who have disease remote from standard pelvic radiation fields or who harbor macroscopically involved pelvic and/or paraaortic nodes are at increased risk for treatment failure have led many authors to recommend surgical staging for patients with this disease. The current study demonstrates that a laparoscopic approach to such surgery is technically feasible and, in experienced hands, demonstrates no increased risk of short-term morbidity. Moreover, there is no significant delay in initiation of radiation therapy. Whether long-term radiation-associated morbidity among patients who undergo laparoscopically directed lymphadenectomy will compare favorably with the low incidence of complications described among patients in whom a retroperitoneal approach is employed awaits further investigation. REFERENCES 1. Piver, M. S., and Chung, W. S. Prognostic significance of cervical lesion size and pelvic node metastases in cervical carcinoma, Obstet. Gynecol. 46, 507–510 (1975). 2. Creasman, W. T. New gynecologic cancer staging, Gynecol. Oncol. 58, 157–158 (1995). 3. Averette, H. E., Dudan, R. C., and Ford, J. H. Exploratory celiotomy for surgical staging of cervical cancer, Am. J. Obstet. Gynecol. 113, 1090–1096 (1972). 4. LaPolla, J. P., Schlaerth, J. B., Gaddis, O., and Morrow, C. P. The influence of surgical staging on the evaluation and treatment of patients with cervical carcinoma, Gynecol. Oncol. 24, 194–206 (1986). 5. Piver, M. S., Barlow, J. J., and Krishnamsetty, R. Five year survival (with no evidence of disease) in patients with biopsy confirmed aortic node metastasis from cervical carcinoma, Am. J. Obstet. Gynecol. 139, 575–578 (1981). 6. Oumakli, A., and Bonney, W. A., Jr. Exploratory laparotomy as routine pretreatment investigation in cancer of the cervix, Radiology 104, 371– 377 (1972).

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7. Rutledge, F., Galakatos, A. E., Wharton, J. T., and Smith, J. P. Adenocarcinoma of the uterine cervix, Am. J. Obstet. Gynecol. 122, 236 (1975). 8. Nelson, J. H., Boyce, J., Macasaet, M., Lu, T., Bohorquez, J. F., Nicastri, A. D., Fruchter, R. Incidence, significance, and follow up of paraaortic lymph node metastases in late invasive carcinoma of the cervix, Am. J. Obstet. Gynecol. 128, 336–340 (1977). 9. Piver, M. S. The value of pretherapy paraaortic lymphadenectomy for carcinoma of the cervix uteri, Surg. Gynecol. Obstet. 145, 17–18 (1977). 10. Potish, R. A., Twiggs, L. B., Okagaki, T., Prem, K. L. A., and Adcock, L. L. Therapeutic implications of the natural history of advanced cervical cancer as defined by pretreatment surgical staging, Cancer 56, 956– 960 (1985). 11. Downey, G. O., Potish, R. A., Adcock, L. L., Prem, K. A., and Twiggs, L. B. Pretreatment surgical staging in cervical carcinoma: Therapeutic efficacy of pelvic lymph node resection, Am. J. Obstet. Gynecol. 160, 1055–1061 (1989). 12. Childers, J. M., Hatch, K., and Surwit, E. A. The role of laparoscopic lymphadenectomy in the management of cervical carcinoma, Gynecol. Oncol. 47, 38–43 (1992). 13. Querleu, D., Leblanc, E., and Castelain, B. Laparoscopic pelvic lymphadenectomy in the staging of early carcinoma of the cervix, Am. J. Obstet. Gynecol. 164, 579–581 (1991). 14. Fowler, J. M., Carter, J. R., Carlson, J. W., Maslonkowski, R., Byers, L. J., Carson, L. F., and Twiggs, L. B. Lymph node yield from laparoscopic lymphadenectomy in cervical cancer: A comparative study, Gynecol. Oncol. 51, 187–192 (1993). 15. Hasson, H. M. Open laparoscopy: A modified instrument and method of laparoscopy, Am. J. Obstet. Gynecol. 110, 886–887 (1971). 16. American Joint Commission on Staging of Cancer. Cancer manual of staging of cancer, 4th ed., Lippincott, Philadelphia, PA (1991). 17. Delgado, G., Bundy, B. N., Fowler, W. C., Jr., Stehman, F. B., Sevin, B., Creasman, W. T., Major, F., DiSaia, P., and Zaino, R. A prospective surgical pathological study of stage I squamous carcinoma of the cervix: A Gynecologic Oncology Group Study, Gynecol. Oncol. 35, 314–320 (1989). 18. Delgado, G., Bundy, B., Zaino, R., Sevin, B. U., Creasman, W. T., and Major, F. Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: A Gynecologic Oncology Group Study, Gynecol. Oncol. 38, 352–357 (1990). 19. Delgado, G., Caglar, H., and Walker, P. Survival and complications in cervical cancer treated by pelvic and extended field radiation after paraaortic lymphadenectomy, AJR 130, 141 (1985). 20. Piver, M. S., Hempling, R. E., and Craig, K. A. Neoplasms of the cervix, in Cancer medicine (J. F. Holland, E. Frei, R. C. Bast, D. W. Kufe, D. L. Morton, and R. R. Weichselbaum, Eds.), Lea & Febiger, Malvern, PA, 3rd ed., pp. 1631–1646 (1993). 21. Hricak, H., Lacey, C. G., Sandles, L. G., Chang, Y. C. F., Winkler, M. L., and Stern, J. L. Invasive cervical carcinoma: comparison of MR imaging and surgical findings, Radiology 166, 622–631 (1988). 22. Waggenspak, G. A., Amparo, E. G., and Hannigan, E. V. MR imaging of cervical carcinoma, J. Comput. Assist. Tomogr. 12, 409–414 (1988). 23. Su, T. H., Wang, K. G., Yang, Y. C., Hong, B. K., and Huang, S. H. Laparoscopic paraaortic lymph node sampling in the staging of invasive cervical carcinoma: Including a comparative study of 21 laparotomy cases, Int. J. Gynecol. Obstet. 49, 311–318 (1995). 24. Spirtos, N. M., Schlaerth, J. B., Spirtos, T. W., Schlaerth, A. C., Indman, P. D., and Kimball, R. E. Laparoscopic bilateral pelvic and paraaortic lymph node sampling: an evolving technique, Am. J. Obstet. Gynecol. 173, 105–111 (1995).

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