Minimally Invasive Radical Hysterectomy

Jason D. Wright, MD: Jason D. Wright, MDFor many decades, radical hysterectomy has been the surgical procedure of choice for early-stage cervical cancer. The operation allows for the en bloc removal of the uterus and cervix with the surrounding parametrial tissue, upper vagina, and uterosacral ligaments. Although radical hysterectomy is associated with excellent oncologic outcomes, it is also accompanied by substantial morbidity. Use of minimally invasive surgical techniques to perform radical hysterectomy was first reported in the early 1990s. Over the preceding two decades, a number of case series emerged describing the feasibility of both laparoscopic and robotic-assisted radical hysterectomy. Early evaluations of minimally invasive radical hysterectomy focused largely on short-term morbidity and noted that perioperative complication rates were lower for minimally invasive compared with open radical hysterectomy. However, there were few data describing the oncologic outcomes of the procedure or long-term survival. Despite the lack of cancer-specific outcomes data, the rise of minimally invasive radical hysterectomy was rapid, and, by 2010, one-third of radical hysterectomies for cervical cancer were minimally invasive.1 Perceptions of the safety of minimally invasive radical hysterectomy were challenged in 2018 with publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial. This multinational study randomized more than 600 patients with stage IA1–IB1 cervical cancer to either open or minimally invasive radical hysterectomy. The study was closed early after finding a significant increase in the risk of recurrence for patients who underwent minimally invasive surgery, with disease-free survival at 4.5 years of 96% for those who underwent open surgery compared with 85% after minimally invasive surgery (hazard ratio 3.74).2 At the same time, a large observational study found that performance of radical hysterectomy using minimally invasive techniques was associated with a 65% increase in mortality.3 Although there initially was skepticism about the findings of these two studies, a series of reports from many countries were subsequently published and noted similar findings of decreased survival with minimally invasive radical hysterectomy.4 Although the uptake of minimally invasive radical hysterectomy was rapid, the decline in use of the procedure was even more precipitous.5 After publication of the LACC trial, questions were immediately raised as to how a procedure with minimal oncologic safety data could diffuse so widely and become an accepted standard of care for early-stage cervical cancer. A number of factors likely converged to drive use of minimally invasive radical hysterectomy. First, during the time period, use of minimally invasive surgery increased rapidly in gynecology and was demonstrated to be safe for endometrial cancer.6 Second, robotic-assisted surgery emerged as an alternative to laparoscopy to facilitate performance of more complex minimally invasive procedures. The technology was heavily marketed to patients and clinicians. Lastly, there is little formal regulation of procedures. Although consensus groups have called for a graduated diffusion of new procedures with concurrent dissemination of evidence of safety and efficacy, this process often is circumvented when enthusiasm for a procedure outpaces evidence.7 Given the safety concerns for minimally invasive radical hysterectomy, many advocated that the procedure be abandoned for patients with cervical cancer. There was also intense speculation as to the underlying mechanism responsible for the decreased survival rate associated with minimally invasive surgery. The most plausible theory to emerge was that the surgical technique used for minimally invasive surgery was responsible for intraperitoneal dissemination of tumor cells. Minimally invasive radical hysterectomy typically was performed using a uterine manipulator that could disrupt the cervical tumor, particularly with prolonged manipulation. Similarly, performance of colpotomy directly exposes the tumor to the peritoneal cavity. Proponents of minimally invasive radical hysterectomy argued that the procedure should not be abandoned entirely and that, with proper technique, it could be a safe operation in appropriately selected patients. In this month's issue of Obstetrics & Gynecology, Li et al8 (see page 134) test the hypothesis that intraoperative tumor manipulation promotes occult dissemination of malignant cells. The authors developed and tested a modified tumor-free technique for laparoscopic radical hysterectomy for early-stage cervical cancer. The modified tumor-free technique relies on several surgical modifications, including suspension of the uterine fundus with a suture for manipulation instead of use of a uterine manipulator, protective closure of the vagina before colpotomy, and coagulation of the fallopian tubes. The authors collected data on 151 patients after the introduction of these techniques and compared them with data from a group of 125 historical control patients. After 24 months of follow-up, the recurrence rate was 0.7% in the modified tumor-free technique group compared with 8% in the control group, with 2-year disease-free survival rates of 99.3% and 91.7%, respectively. These findings were robust in several sensitivity analyses, including after propensity-score balancing. Although the study provides proof of concept, there are notable limitations, including underlying selection bias in which patients with more favorable oncologic factors underwent modified tumor-free radical hysterectomy, a small sample size with limited follow-up, comparison with a historical control group, and performance of the procedure by a small number of surgeons at a very high-volume center.8 Other emerging data also have provided support for the concept of limiting tumor exposure for minimally invasive radical hysterectomy. Final analysis of the LACC data found that patients who underwent preoperative conization with removal of the bulk of the primary tumor were at no increased risk of recurrence with minimally invasive surgery compared with laparotomy.9 A multicenter observational study noted that patients who underwent minimally invasive radical hysterectomy with a uterine manipulator were at significantly increased risk of relapse. Those who had minimally invasive surgery without a manipulator had recurrence rates similar to open surgery.10 This group also noted that preoperative conization was associated with a protective effect.11 Where do we go from here? Although the surgical modifications described are intriguing, minimally invasive radical hysterectomy for cervical cancer should be approached with caution. The procedure generally should be undertaken in the setting of a clinical trial, and it would appear prudent to minimize tumor disruption and exposure to the peritoneal cavity. Patients must weigh the risks and benefits of the procedure. Although often overlooked, the LACC trial also called into question the ability of minimally invasive surgery to reduce the morbidity of radical hysterectomy, the impetus for development of the procedure in the first place. Among participants, the rates of intraoperative and postoperative adverse events and quality of life were similar for open and minimally invasive procedures.12,13 To help define these risks and understand patient preferences, future studies should incorporate patient-reported outcomes and facilitate decision making by individual patients. Although minimally invasive radical hysterectomy still may find a role in the treatment of cervical cancer, the procedure serves as a reminder that innovation must be accompanied by evidence.