Because of the high-level evidence in favor of open surgery provided by the randomized LACC trial, the use of LRH in the treatment of cervical cancer has been questioned a lot in the past 2 years (14). In the present study, we showed that the survival outcomes are acceptable in patients with early-stage cervical cancer undergoing conventional laparoscopic surgery at our center, where the mean yearly LRH volume was 131.6 cases. In addition, the learning curve is a critical factor affecting survival, suggesting that minimally invasive surgery remains an effective treatment option for patients with early-stage cervical cancer.
Generally, the survival after LRH in patients with stage IA-IB1 cervical cancer is satisfying but varies across studies, with a 5-year PFS rate ranging from 80.2–96.3% (5, 8, 15). In the present study, we also report a high 4-year PFS of 92.0% in patients, which is not inferior to that in the open surgery group of the LACC trial. Recently emerging evidence from non-randomized studies and meta-analyses comparing survival after minimally invasive surgery versus abdominal surgery for early-stage cervical cancer remains controversial, with some results showing compromised oncologic outcomes related to minimally invasive surgery, while others did not (2, 5, 6, 16–18). However, the application of LRH for tumors of less than 2 cm in size was supported by its non-inferior survival compared to laparotomy demonstrated by numerous studies, even by those showing increased recurrence and death risk after minimally invasive surgery (19–21). Additionally, we found that patients with < 2 cm squamous cell carcinoma, which can be identified preoperatively, had excellent survival outcomes after LRH. This subpopulation would be particularly benefit from laparoscopy with fewer morbidities, shorter hospital stays, and non-compromised survival.
It is evident that surgical proficiency is a critical determinant of oncologic outcomes after surgery. We showed a poorer OS in the first 50 cases of LRH performed in our center, which was gradually improved in successive operations and reached a plateau after 100 LRHs. In patients operated on by the same surgeon, an improvement in survival was observed after 40 LRHs, suggesting that intensive practice is required to ensure the oncologic safety of surgery. Similarly, the impact of the learning curve on the oncologic outcomes of surgery for cervical cancer has been reported in two recent studies in the wake of the LACC trial (8, 9). Moreover, the surgery volume has been identified as an independent factor for survival. In 116 surgery centers in Japan, a high surgery volume (105 cases or more within 5 years) of LRH and systematic pelvic lymphadenectomy has been identified as a significant protective factor for PFS (HR, 0.69; 95% CI, 0.57–0.84) and OS (HR, 0.75; 95% CI, 0.59–0.95) in cervical cancer patients, while a medium-low volume (less than 105 cases within 5 years) was not protective (22). A population-based retrospective cohort study from Canada identified 958 patients undergoing primary radical hysterectomy from 2006 to 2017 (475 minimally invasive procedures and 483 abdominal procedures) and showed increased recurrence and death in patients with stage IB cervical cancer after controlling for surgeon volume; however, the median cervical cancer volume in terms of radical hysterectomy (the number of hysterectomies performed in the 2 years prior to the indexed procedure) of 8 (range 4–12) appears generally low, being insufficient to definitively exclude the impact of surgeon volume on the survival outcomes (17). Generally, minimally invasive surgery demands more learning and practice than open surgery because of the complexity of the procedure, and the learning curve would be further prolonged in centers with low patient volume. Given the extremely imbalanced prevalence of cervical cancer around the world, with approximately 90% of newly diagnosed cases occurring in low-resource countries and few occurring in developed countries, and the significant disparities in laparoscopic proficiency and competence between counties, centers and surgeons, a global consensus on the surgical approach to cervical cancer seems difficult to achieve, and country- or center-based recommendations might be more meaningful.
The intraoperative assessment of tumor and lymph node potential risks and improvements for laparoscopic surgery for cervical cancer have been intensively discussed in the past two years. Laparoscopic vaginal dissection and cuff closure, the use of a uterine manipulator, and the CO2 pneumoperitoneum are considered to be processes potentially causing nosocomial dissemination of cervical cancer cells (23, 24). All these were used in the patients we studied. Several studies have provided retrospective evidence supporting some improvements in LRH to prevent possible tumor cell spillage. The survival after LRH with the “no-look no-touch technique” for stage IB1 tumors was found to be equal to that after open surgery (15). A multicenter analysis of 389 patients showed that LRH with transvaginal closure of the vaginal cuff avoided the use of a manipulator and offered oncologic outcomes similar to those of the laparotomy arm in the LACC trail (25). The use of a surgical stapler is also an option for vaginal closure to avoid tumor cell spillage (26). The potential benefits regarding oncologic safety of these adjustments need to be tested in randomized controlled trials.
Despite the relatively large number of patients involved, the limitations associated with the single-center, retrospective study design of the present study, such as selection bias and confounding bias, cannot be ignored. The missing data in the long-term follow-up of patients represents a major issue. Unfortunately, the median follow-up time was only 48 months, making an accurate estimation of the 5-year survival rate difficult. In addition, approximately 15% of patients were lost to follow-up, which might lead to some bias in the survival analysis. Further studies with long-term follow-up are needed to further clarify the oncologic outcomes after LRH in patients with early-stage cervical cancer.