Randomized trial of surgical staging (extraperitoneal or laparoscopic) versus clinical staging in locally advanced cervical cancer☆

Abstract

Objective

To define the role of pretreatment surgical staging for locally advanced cervical carcinoma.

Methods

A two-step randomized trial was conducted to compare clinical staging (arm A) versus surgical staging (arm B) and to compare the laparoscopic (LAP) with the extraperitoneal (EXP) approach in previously untreated locally advanced cervical carcinoma. After the first randomization, those in arm B were randomly allocated to either LAP or EXP. An interim analysis was planned to evaluate the feasibility of LAP versus EXP, which led to the current report.

Results

A total of 61 patients were eligible (arm A, 29; arm B, 32). The operation time, blood loss, and lymph node yield of LAP and EXP were not significantly different. Serious acute and late toxicity was not different between arm A and arm B, or LAP versus EXP. Para-aortic node metastasis was documented in 25% (95% confidence interval, 10% to 40%) of patients on arm B. An interim analysis was performed in January 2000. Patients on arm B had significantly worse progression-free survival than those on arm A. Hazard ratios of relapse/persistent or death were 3.13 (P = 0.005) and 1.76 (P = 0.150), respectively. Patient accrual was terminated according to the early stopping rules. With further follow-up till December 2001, the difference in progression-free survival remained significant (P = 0.003), and the difference in overall survival became significant (P = 0.024) as the data matured.

Conclusion

The benefit of pretreatment surgical staging for cervical carcinoma remained unproven. The detrimental effects of surgical staging observed in this study must be considered in the design of clinical guidelines or future trials.

Introduction

For locally advanced cervical cancer (stage IIB–IV), irradiation to the primary tumor and pelvic lymph nodes is the mainstay treatment. Conventional whole-pelvis external irradiation plus brachytherapy may control tumors still confined to the pelvis but fail to control those spreading outside of the pelvis. Lymphatic spread is one of the main routes of metastasis of cervical cancer. Nodal metastasis (especially para-aortic nodes) is associated with worst prognosis in a pooled population of patients treated with primary radiation in the Gynecologic Oncology Group studies [1].

Generally, extended-field radiation is prescribed with documented para-aortic node metastasis; however, high intestinal complications are noted with transperitoneal laparotomy in addition to high total and fraction dose in the earlier reports [2], [3], [4], [5]. Prophylactic extended-field radiotherapy has been used in locally advanced cervical cancer with no conclusive improvement in the increase of survival rates with the cost of increased morbidity [6], [7]. Ideally, benefit could be maximal if extended-field radiotherapy is given only to those who have documented para-aortic node metastasis [4].

Clinical staging of cervical carcinoma using imaging methods such as computerized tomography (CT) scan/magnetic resonance imaging, ultrasound, or lymphangiography has been suboptimal in detecting metastasis to para-aortic lymph nodes. The sensitivity ranged from 19% to 79% [8], [9], [10]. The use of pretreatment surgical staging for locally advanced cervical carcinoma has been advocated [2], [3], [4], [11], [12], [13], [14], [15], [16], [17] yet unproven by randomized controlled trials (RCTs). Pretreatment surgical staging by the extraperitoneal approach appears to be associated with less long-term radiation morbidity compared with the transperitoneal approach, probably because of reduced postoperative intra-abdominal adhesion [3], [17]. With the advancement in laparoscopic surgery, several groups could perform a satisfactory retroperitoneal lymph node dissection with minimal intra-abdominal manipulation, which may allow a decrease in adhesion formation [11], [12], [18], [19].

Our aim was to do a prospective randomized, controlled study to evaluate the benefit of surgical staging in comparison with clinical staging. We also planned to compare extraperitoneal (EXP) with laparoscopic (LAP) approach in the surgical staging group. An interim analysis was planned when one-half of the intended number of patients had been enrolled to evaluate the feasibility and efficacy of LAP versus EXP, which led to the current report.