A proof-of-concept randomized phase 2 non-inferiority trial on simple versus modified radical hysterectomy in IA2-IB1 cervical cancer ≤2cm (LESSER)

Abstract

Objectives: To evaluate the safety and efficacy of simple hysterectomy in early stage cervical cancer. Methods: The LESSER (LESs Surgical radicality for EaRly stage cervical cancer) study was a proof of concept randomized phase 2 non-inferiority trial evaluating the safety and efficacy of simple hysterectomy compared to modified radical hysterectomy in patients with stages IA2-IB1 cervical cancer and tumors of ≤2cm in size. Primary end-point was 3y-DFS rates and secondary endpoints were 3y-OS (3-year overall survival), surgical morbidity, indication of adjuvant therapy, and QoL (EORTC QLQ-C30). The study was registered at ClinicalTrials. gov (NCT02613286). Results: A total of 40 patients were randomized 1:1 from May 2015 to April 2018 in 3 oncological centers from Northeast Brazil. All cases had pelvic systematic lymph node dissection. Overall, 10% of patients underwent MIS procedures, 80% of tumors were SCC and 7.5% had lymph node metastasis, whereas inaccuracies for clinical tumor size estimation, LVSI and stromal invasion > 1 cm were found in 20%, 22.5% and 30% of cases, respectively. Clinical and pathological characteristics were well balanced between treatment arms, but the length of surgery and the time for bladder catheterization removal were higher after radical hysterectomy (p=0.003 and p=0.043, respectively). There was no postoperative mortality and rates of any grade postoperative complication were not statistically different between arms (15% and 20%; p=1.00). No major differences in the QoL over time were also observed. A quarter of patients received adjuvant therapy, with no significant difference between groups (30% vs. 20%, p=0.48). There was one death at 25 months of follow-up due to pelvic recurrence in the simple hysterectomy arm. A pathological review of this case found tumor embolus in the lymphovascular space of left parametrium that was missed at the time of former anatomopathological analysis. Another patient died of lung metastasis from a second primary thyroid cancer at 54.4 months of follow-up in the radical hysterectomy arm. A major late complication was also recorded after 3 months from radical surgery in a patient with distal urethral stenosis that was treated with segmental resection and psoas-hitch ureteroneocystostomy. Survival outcomes with a minimum of 3y follow-up will be mature for presentation during the SGO 2021 Annual Meeting on Women's Cancer. Conclusions: Simple hysterectomy is a promising substitute for modified radical hysterectomy in stage IA2-IB1 cervical cancer ≤2cm. To evaluate the safety and efficacy of simple hysterectomy in early stage cervical cancer. The LESSER (LESs Surgical radicality for EaRly stage cervical cancer) study was a proof of concept randomized phase 2 non-inferiority trial evaluating the safety and efficacy of simple hysterectomy compared to modified radical hysterectomy in patients with stages IA2-IB1 cervical cancer and tumors of ≤2cm in size. Primary end-point was 3y-DFS rates and secondary endpoints were 3y-OS (3-year overall survival), surgical morbidity, indication of adjuvant therapy, and QoL (EORTC QLQ-C30). The study was registered at ClinicalTrials. gov (NCT02613286). A total of 40 patients were randomized 1:1 from May 2015 to April 2018 in 3 oncological centers from Northeast Brazil. All cases had pelvic systematic lymph node dissection. Overall, 10% of patients underwent MIS procedures, 80% of tumors were SCC and 7.5% had lymph node metastasis, whereas inaccuracies for clinical tumor size estimation, LVSI and stromal invasion > 1 cm were found in 20%, 22.5% and 30% of cases, respectively. Clinical and pathological characteristics were well balanced between treatment arms, but the length of surgery and the time for bladder catheterization removal were higher after radical hysterectomy (p=0.003 and p=0.043, respectively). There was no postoperative mortality and rates of any grade postoperative complication were not statistically different between arms (15% and 20%; p=1.00). No major differences in the QoL over time were also observed. A quarter of patients received adjuvant therapy, with no significant difference between groups (30% vs. 20%, p=0.48). There was one death at 25 months of follow-up due to pelvic recurrence in the simple hysterectomy arm. A pathological review of this case found tumor embolus in the lymphovascular space of left parametrium that was missed at the time of former anatomopathological analysis. Another patient died of lung metastasis from a second primary thyroid cancer at 54.4 months of follow-up in the radical hysterectomy arm. A major late complication was also recorded after 3 months from radical surgery in a patient with distal urethral stenosis that was treated with segmental resection and psoas-hitch ureteroneocystostomy. Survival outcomes with a minimum of 3y follow-up will be mature for presentation during the SGO 2021 Annual Meeting on Women's Cancer. Simple hysterectomy is a promising substitute for modified radical hysterectomy in stage IA2-IB1 cervical cancer ≤2cm.