Neoadjuvant chemotherapy and radical surgery versus chemorradiation for stage IB2, IIA2 e IIB cervical cancer: A randomized controlled trial

Abstract

Background: Chemoradiation is the current standard of care for advanced cervical cancer, however radiation is associated with long term side effects that may impair the quality of life of survivors. Recent findings from observational and case series suggest that women with stage IB2, IIA, and IIB who respond to neoadjuvant chemotherapy might be a candidate for radical surgery as the definitive treatment. This approach can reduce long‐term complications associated with chemoradiation and improve patient quality of life. Trial design: Eligible patients are women aged ≥18y diagnosed with invasive cervical cancer stages IB2, IIA or IIB. The stage will be assessed by clinical examination and confirmed by pelvic MRI, CT of upper abdomen and CT of thorax. ECOG PS 0‐1 and adequate organ function are required. Two hundred and forty‐four patients will be randomly assigned to one of two arms. In arm 1, patients will receive standard chemoradiation (cisplatin 40mg/m2 IV: D1, D8, D15, D29 and D36 in concomitancy with external radiation 50.4Gy fractionated in 28 sessions of 1,8Gy followed by brachytherapy in four insertions of 7 Gy). In arm 2, patients will receive intravenous neoadjuvant chemotherapy (cisplatin 75mg/m2 D1 plus paclitaxel 80mg/m2) D1, D8 e D15, each 21 days, 3 cycles. After each cycle, the patient will be evaluated to verify toxicity and tumor response. After the third cycle, the patients with a complete clinical response or substantial tumor reduction (tumor restricted to cervix ≤4 cm), confirmed by pelvic MRI will undergo Piver‐Rutledge class III abdominal hysterectomy and pelvic lymphadenectomy 3‐6 weeks after the last cycle. Patients with tumor progression or severe toxicity after any cycle of neoadjuvant chemotherapy, or with inoperable tumor after the third cycle of neoadjuvant chemotherapy will be treated with definitive standard chemoradiation. The primary end point will be 5‐years overall survival. Secondary endpoints will include survival free of disease, the rate of operability and complete pathological response in the neoadjuvant arm. The study is ongoing; one patient has been included, and three more are under preliminary evaluation for eligibility.