Oncologic and functional outcomes after robot-assisted radical hysterectomy for cervical cancer

Abstract: Background: Cervical cancer is the fourth most common cancer in women worldwide, but the incidence has rapidly declined in developed countries after the introduction of structured screening programs. This disease is caused by persistent HPV infection commonly acquired in adolescence, thereby affecting young women. In countries with established screening programs, early detection has resulted in favorable prognosis. Surgical treatment is the main treatment for early-stage disease and radical hysterectomy (RH) cures more than 90% of those afflicted. However, this treatment is associated with considerable morbidity and impaired quality of life (QoL). In 2005, robot-assisted laparoscopic radical hysterectomy (RRH), was introduced and subsequently implemented in Sweden. The perceived benefits of minimally invasive surgery (MIS), and of RRH in particular, have not been confirmed. It is therefore imperative to assess the efficacy and safety of this surgical technique, as well as short- and long-term adverse effects, particularly since long-term survival is expected. Aims: The overall aim was to investigate the oncologic safety of RRH. Secondary aims included assessment of surgical outcomes, health care costs and impact on QoL, bladder, bowel, sexual and lymphatic function after RRH. Methods: To assess the oncologic and surgical outcomes, two population-based studies were performed (Studies I and II). Study I included 304 women who underwent RH stage IA1-IIA during 2006-2015 at Karolinska University Hospital (KUH). Surgical and oncologic outcomes, as well as the costs of RRH and open radical hysterectomy (ORH) were compared. Study II, a nationwide cohort study, assessed overall and disease-free survival after RRH and ORH in 864 women with stage IA1-IB1 disease. The functional impact of RRH was investigated in two prospective clinical studies (Studies III and IV) with one-year follow-up. In Study III, 26 women undergoing RRH filled in a questionnaire regarding psychological well‐being and sexual, bowel, bladder, and lymphatic function. In addition, postoperative ovarian function was measured by change in sex hormones. In Study IV, 27 patient-reported outcomes after RRH were assessed using two validated questionnaires concerning bladder function and its impact on QoL. Outcomes were determined objectively by urodynamics and quantification of ablated autonomic nerves. Results: In the regional study (Study I), RRH was associated with an increased risk of recurrence (HR 2.13; 95% CI, 1.06-4.26). The postoperative complication rates (37%) and costs were similar, but the hospital stay was shorter than following ORH. The nationwide study (Study II) showed no statistical difference between RRH and ORH with respect to 5-year OS (HR 1.00; 95% CI, 0.50-2.01) and DFS (HR 1.08; 95% CI, 0.66-1.78). Study III demonstrated that RRH had a minor effect on sexual function, as well as bowel function. However, bladder impairment and lymphedema remained the main dysfunctions associated with RRH for cervical cancer (Studies III and IV). No correlation between the number of autonomous nerves ablated and functional outcomes was observed. In general, postoperative urinary symptoms diminished over time, but persisted in a substantial proportion of the women and may impair QoL. Conclusions: RRH appears to be safe once surgical proficiency is achieved. Prospective trials are needed to ensure the safety of RRH for cervical cancer. RRH was associated with less perioperative morbidity, and health care costs were similar to those of ORH. RRH seems to have only minor effects on sexual function, though bladder dysfunction remains a significant sequele. The cause of functional impairment after RRH is multifactorial and cannot be explained by nerve ablation alone.