Shortened Survival With Minimally Invasive Surgery for Cervical Cancer

Treatment for patients with early-stage cervical cancer most often includes radical hysterectomy, which is associated with cure in more than 80% of patients. In recent years, minimally invasive surgery (laparoscopic or robotic) has largely replaced laparotomy (open abdominal surgery) as the preferred surgical method due to a decrease surgical morbidity associated with less invasive procedures. However, no study to date has evaluated the impact of minimally invasive surgery on long-term disease-related outcomes in patients with early-stage cervical cancer. Recently, findings from two trials important for clinical practice were published in The New England Journal of Medicine.

The large, prospective, multicenter, randomized phase III Laparoscopic Approach to Cervical Cancer (LACC) trial compared minimally invasive surgery to open abdominal hysterectomy in 631 patients with early-stage cervical cancer (IA1-IB1) with either squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma histology. Most patients had stage IB1 cancer (91.9%), and over 67% had squamous cell histology. There were no significant differences between the two groups in terms of histology, a tumor grade, tumor size, lymphovasular invasion, parametrial and lymph-node involvement, and use of adjuvant therapy. The rate of intraoperative and early (< 6 weeks) postoperative complications were also similar. The trial closed prematurely after an interim analysis demonstrated a lower 4.5-year disease-free survival with minimally invasive surgery than with open surgery (86% vs 96.5%) and a lower 3-year rate of overall survival (93.8% vs 99.0%; HR 6.00).

Similar results were observed in an epidemiological cohort study that evaluated all-cause mortality among 2,461 patients with stage IA2 or IB1 cervical cancer undergoing radical hysterectomy in the United States in an attempt to identify the impact of minimally invasive surgery compared to laparotomy. Approximately half of patients (49.8%) included in this analysis underwent minimally invasive surgery. Minimally invasive surgery was more common among patients who were white, had private insurance, and came from areas of higher socioeconomic status, as well as those with smaller, low-grade tumors, and those diagnosed later in the study period. After a median follow-up of 45 months, 4-year mortality was 9.1% for women who had minimally invasive surgery, compared to 5.3% in women who had laparotomy, corresponding to a 65% higher risk of death (HR 1.65, P = .002). There were no differences between the two cohorts in histopathological variables and adjuvant therapy (chemotherapy and radiotherapy). Exploratory analyses found a higher risk of death associated with robot-assisted radical hysterectomy and traditional laparoscopic hysterectomy than open surgery (HR 1.61 and 1.50, respectively).

Prior to the introduction of minimally invasive surgery, the 4-year relative survival rate associated with radical hysterectomy was stable, while the adoption of minimally invasive surgery was associated with a decline in 4-year survival of 0.8% per year (P = .01).

The investigators concluded that minimally invasive surgery for early-stage cervical cancer results in worse overall survival than laparotomy, potentially by limiting the extent of resection or by facilitating spread of tumor cells through use of uterine or cervical manipulators and carbon dioxide gas. In an accompanying editorial, the authors highlighted that ‘’although these data are alarming, select patients may still benefit from a less invasive procedure.’’ However, until more details are known, they advise surgeons to be cautious, discuss results of these studies with their patients, and carefully assess the risks and benefits of both surgical approaches for each patient. Importantly, these studies indicate the need to focus on both clinical and surgical outcomes when evaluating new surgical techniques, rather than surgical outcomes alone.

N Engl J Med. 2018;379(20):1895-1904.

N Engl J Med. 2018;379(20:1905-1914.

N Engl J Med. 2018;379(20):1955-1957.