Proof-of-concept randomized phase II non-inferiority trial of simple versus type B2 hysterectomy in early-stage cervical cancer ≤2 cm (LESSER).

OBJECTIVE: To evaluate the non-inferiority and safety of simple hysterectomy in early stage (<2 cm) cervical cancer. METHODS: This proof-of-concept randomized phase II non-inferiority trial was performed between May 2015 and April 2018 in three oncological centers in Northeast Brazil. Patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stages IA2-IB1 cervical cancer and tumors ≤2 cm were treated with either simple or modified radical hysterectomy (Querleu-Morrow type B2). Intention-to-treat analysis was carried out. The primary endpoint was 3-year disease-free survival and secondary endpoints were overall survival, operative outcomes, adjuvant therapy, and patient's health-related quality of life (QoL). RESULTS: A total of 40 patients underwent either simple hysterectomy (n=20) or modified radical hysterectomy (n=20). All patients except three underwent open procedures (n=37/40, 92.5%). At a median follow-up of 52.1 months (IQR 43.9-60.1), 3-year disease-free survival was 95% (95% CI 68% to 99%) after simple hysterectomy and 100% (95% CI 100% to 100%) after modified radical hysterectomy (log-rank p=0.30). The corresponding 5-year overall survival rates were 90% (95% CI 64% to 97%) and 91% (95% CI 50% to 98%), respectively (log-rank p=0.46). The operative time was shorter after simple hysterectomy than after modified radical hysterectomy (150 min (IQR 137.5-180) vs 199.5 min (IQR 140-230); p=0.003), with a trend towards a longer time for vesical catheterization removal (1 day (IQR 1-1) vs 1 day (IQR 1-2); p=0.043). There was no post-operative mortality and the rates of post-operative complications were not statistically different between arms (15% and 25%; p=0.69). QoL questionnaires were received from only 17 patients (42.5%), with no major differences observed over time between the surgical arms. CONCLUSIONS: Simple hysterectomy is safe and potentially non-inferior to the radical surgery in patients with early-stage cervical cancer ≤2 cm. TRIAL REGISTRATION NUMBER: NCT02613286.

Phase II trial of neoadjuvant chemotherapy followed by chemoradiation in locally advanced cervical cancer.

OBJECTIVE: Cervical cancer is a global public health challenge. Since 1999, platin based chemoradiation (CRT) is the standard treatment for those patients with locally advanced disease. However, this population still has a dismal prognosis and, alternatives approaches such as adjuvant chemotherapy are controversial, especially because of increased toxicity. Neoadjuvant chemotherapy (NACT) could be an option for more intensive treatment with manageable toxicity. METHODS: A phase II, prospective, non-randomized trial was conducted at a reference center in Recife, Brazil. Locally advanced cervical cancer patients (Ib2-IVa) were treated with neoadjuvant cisplatin 35mg/m2 and gemcitabine 1000mg/m2 D1 and D8, for 2cycles. Then, they received CRT (50.4Gy) with weekly cisplatin 40mg/m2 followed by brachytherapy. Response rate (RR) and toxicity were the primary endpoints. Progression-free survival (PFS) and overall survival (OS) were secondary endpoints. RESULTS: Between Sep/2013 and Oct/2015, 50 patients were initiated on NACT and CRT. RR was 81% at the end of treatment. Hematological and gastrointestinal toxicity were most common. Grade 3/4 toxicity was 20% during NACT and 44% during CRT. Late adverse events were present in 20% of patients. PFS at 1 and 3-years were 73.4% (IC 58.7-83.6) and 53.9% (IC 36.9-68.3), respectively; and, OS at 1 and 3-years were 93.9% (IC 82.4-98.0) and 71.3% (IC 53.3-83.3), respectively. CONCLUSION: In our hands NACT in locally advanced cervical cancer patients did not show a meaningful improvement in ORR. Nevertheless, we believe it should be further explored in prospective trials.