Robot-assisted laparoscopy and sentinel node biopsy in high risk endometrial cancer

Abstract

Surgery is standard treatment for early stage endometrial cancer (EC), the most common gynaecological malignancy in developed countries. Traditionally, surgery has been performed by laparotomy (LT). Comprehensive surgical staging, including pelvic (PLND) and paraaortic (PALND) lymph node dissection, is associated with morbidity and possible reduction in quality of life. Minimally invasive surgery (MIS) is associated with less morbidity, albeit newer MIS techniques, i.e. robot-assisted laparoscopic surgery (RALS), has not been compared with LT in a randomised setting. The sentinel lymph node technique is well established in other malignancies, however, the experience in EC is limited. The aim of this thesis was to evaluate if RALS for PLND and infrarenal PALND (IRPALND) in women with high risk EC is noninferior to LT in harvesting lymph nodes, to investigate short- and long-term morbidity as well as quality of life. We also wanted to evaluate the sentinel lymph node biopsy concept as a diagnostic tool for detecting lymph node metastases (LNM).

In the RASHEC trial, we randomised 120 women with stage I-II EC with high-risk tumour features to hysterectomy, bilateral salpingo-oophorectomy, PLND and IRPALND by either RALS or LT between 2013 and 2016. Primary endpoint was paraaortic lymph node count. Patient-reported outcome (EORTC QLQ-C30 and the endometrial cancer module EN-24, EQ-5D for generic health status) was assessed before surgery and 12 months after surgery. Computed tomography (CT) was performed at baseline, 3 and 12 months after surgery. Patient characteristics were evenly distributed between the two groups. In the per protocol analysis of 96 patients, difference of means with a 95% confidence interval was within the noninferiority margin for infrarenal paraaortic lymph node count (-1.6, 95% CI -5.78 -2.57). No difference in perioperative complications (Clavien-Dindo classification) or readmissions to hospital within 30 days after surgery was found. RALS was associated with longer operation time (p<0.001) but less total blood loss (p<0.001), shorter hospital stay (p<0.001) and lower health care cost (p<0.05) compared to LT. We found no difference in self-reported lower limb lymphoedema, occurrence of lymphocysts, serious adverse events or admission to hospital for any reason between the two groups 12 months after surgery. Moreover, there was no difference in health-related quality of life.

The Sentinel node in High Risk Endometrial Cancer (SHREC-study) is a prospective nonrandomised trial recruiting consecutive patients from two tertiary referral centres in Sweden (Lund and Stockholm) between 2014 and 2018 where each woman served as her own control. In total 261 patients underwent pelvic sentinel node biopsy followed by completion lymphadenectomy of which 257 were analysed. The sentinel lymph node biopsy algorithm applied in the SHREC-trial demonstrated a sensitivity for detection of LNM of 100% (95% CI 92-100) and a negative predictive value of 100% (95% CI 98-100).

This thesis demonstrates that RALS is non-inferior to LT in harvesting infrarenal paraaortic lymph nodes. RALS was associated with shorter hospital stay and lower health care cost and there were no evident differences in morbidity or quality of life. Consequently, we find RALS to be a valid option for comprehensive surgical staging including IRPALND in high risk endometrial cancer. The choice of surgical modality should be made based on surgeons’ and patient preference. The sentinel lymph node biopsy algorithm has a satisfactory bilateral mapping rate and complete detection of LNM, corroborating previous reports. Gold standard diagnostic lymphadenectomy in women EC should therefore be replaced by the less invasive sentinel lymph node biopsy.