Perioperative morbidity of different operative approaches in early cervical carcinoma: a systematic review and meta-analysis comparing minimally invasive versus open radical hysterectomy.

PURPOSE: Radical hysterectomy and pelvic lymphadenectomy is the standard treatment for early cervical cancer. Studies have shown superior oncological outcome for open versus minimal invasive surgery, but peri- and postoperative complication rates were shown vice versa. This meta-analysis evaluates the peri- and postoperative morbidities and complications of robotic and laparoscopic radical hysterectomy compared to open surgery. METHODS: Embase and Ovid-Medline databases were systematically searched in June 2020 for studies comparing robotic, laparoscopic and open radical hysterectomy. There was no limitation in publication year. Inclusion criteria were set analogue to the LACC trial. Subgroup analyses were performed regarding the operative technique, the study design and the date of publication for the endpoints intra- and postoperative morbidity, estimated blood loss, hospital stay and operation time. RESULTS: 27 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Meta-analysis showed no significant difference between robotic radical hysterectomy (RH) and laparoscopic hysterectomy (LH) concerning intra- and perioperative complications. Operation time was longer in both RH (mean difference 44.79 min [95% CI 38.16; 51.42]), and LH (mean difference 20.96 min; [95% CI - 1.30; 43.22]) than in open hysterectomy (AH) but did not lead to a rise of intra- and postoperative complications. Intraoperative morbidity was lower in LH than in AH (RR 0.90 [0.80; 1.02]) as well as in RH compared to AH (0.54 [0.33; 0.88]). Intraoperative morbidity showed no difference between LH and RH (RR 1.29 [0.23; 7.29]). Postoperative morbidity was not different in any approach. Estimated blood loss was lower in both LH (mean difference - 114.34 [- 122.97; - 105.71]) and RH (mean difference - 287.14 [- 392.99; - 181.28]) compared to AH, respectively. Duration of hospital stay was shorter for LH (mean difference - 3.06 [- 3.28; - 2.83]) and RH (mean difference - 3.77 [- 5.10; - 2.44]) compared to AH. CONCLUSION: Minimally invasive radical hysterectomy appears to be associated with reduced intraoperative morbidity and blood loss and improved reconvalescence after surgery. Besides oncological and surgical factors these results should be considered when counseling patients for radical hysterectomy and underscore the need for new randomized trials.

Protective operative techniques in radical hysterectomy in early cervical carcinoma and their influence on disease-free and overall survival: a systematic review and meta-analysis of risk groups.

PURPOSE: Radical hysterectomy with pelvic lymphadenectomy presents the standard treatment for early cervical cancer. Recently, studies have shown a superior oncological outcome for open versus minimal invasive surgery, however, the reasons remain to be speculated. This meta-analysis evaluates the outcomes of robotic and laparoscopic hysterectomy compared to open hysterectomy. Risk groups including the use of uterine manipulators or colpotomy were created. METHODS: Ovid-Medline and Embase databases were systematically searched in June 2020. No limitation in date of publication or country was made. Subgroup analyses were performed regarding the surgical approach and the endpoints OS and DFS. RESULTS: 30 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Patients were analyzed concerning the surgical approach [open surgery (AH), laparoscopic surgery (LH), robotic surgery (RH)]. Additionally, three subgroups were created from the LH group: the LH high-risk group (manipulator), intermediate-risk group (no manipulator, intracorporal colpotomy) and LH low-risk group (no manipulator, vaginal colpotomy). Regarding OS, the meta-analysis showed inferiority of LH in total over AH (0.97 [0.96; 0.98]). The OS was significantly higher in LH low risk (0.96 [0.94; 0.98) compared to LH intermediate risk (0.93 [0.91; 0.94]). OS rates were comparable in AH and LH Low-risk group. DFS was higher in the AH group compared to the LH group in general (0.92 [95%-CI 0.88; 0.95] vs. 0.87 [0.82; 0.91]), whereas the application of protective measures (no uterine manipulator in combination with vaginal colpotomy) was associated with increased DFS in laparoscopy (0.91 [0.91; 0.95]). CONCLUSION: DFS and OS in laparoscopy appear to be depending on surgical technique. Protective operating techniques in laparoscopy result in improved minimal invasive survival.

Prophylactic HPV vaccination after conization: A systematic review and meta-analysis.

INTRODUCTION: Human papillomavirus (HPV) vaccination is essential for cervical cancer prevention. However, the value of HPV vaccination in the context excisional treatment of high-grade cervical intraepithelial neoplasia (CIN 3) remains unclear. METHODS: In this meta-analysis, three retrospective and three prospective studies, three post-hoc analyses of RCTs and one cancer registry study analysing the effect of pre- or post-conization vaccination (bi- or quadrivalent vaccine) against HPV were included after a systematic review of literature. Random-effect models were prepared to evaluate the influence of vaccination on recurrent CIN 2+. RESULTS: Primary end point was CIN2+ in every study. The overall study population included 21,059 patients (3,939 vaccinations vs. 17,150 controls). The results showed a significant risk reduction for the development of new high-grade intraepithelial lesions after HPV vaccination (relative risk (RR) 0.41; 95% CI [0.27; 0.64]), independent from HPV type. Due to the heterogeneous study population multiple sub analyses regarding HPV type, age of patients, time of vaccination and follow-up were performed. Age-dependent analysis showed no differences between women under 25 years (RR 0.47 (95%-CI [0.28; 0.80]) and women of higher age (RR 0.52 (95%-CI [0.41; 0.65]). Results for HPV 16/18 positive CIN2+ showed a RR of 0.37 (95% CI [0.17; 0.80]). Overall, the number of women that would have to be vaccinated before or after conization to prevent one case of recurrent CIN 2+ (NNV) is 45.5. CONCLUSION: Meta-analysis showed a significant risk reduction of developing recurrent cervical intraepithelial neoplasia after surgical excision and HPV vaccination compared to surgical excision only.