The main objective of this study is to determine whether neoadjuvant chemotherapy with Carboplatin and paclitaxel plus standard cisplatin-based chemoradiation with extended fields improves overall survival rates compared to standard therapy alone in women with cervical cancer with paraaortic lymph node involvement.

Women in the experimental arm will receive neoadjuvant chemotherapy with carboplatin and paclitaxel every 21 days during 3 cycles followed by standard therapy with extended field external radiation therapy and concomitant chemotherapy. Women in the control arm will receive standard therapy with extended field external radiation therapy and concomitant chemotherapy.

310 patients will be recruited during 4.5 years, with 3 years of follow up period.

The survival outcome of patients with carcinoma of the cervix and positive paraaortic lymph node is poor and the potential benefit of neoadjuvant chemotherapy before extended field chemoradiotherapy has never been assessed.

Paraaortic nodal spread in cervical cancer is a blind spot in the management of cervical cancer. It is necessary to evaluate additional treatment.

While the presence of paraaortic nodal metastases often indicates occult systemic disease, the investigators continue to treat them as a loco-regional disease.

Using neoadjuvant chemotherapy, improvement of overall survival rates is expected in women with cervical cancer and para-aortic positive lymphadenopathy without increasing the incidence of further toxicity.

The propose is to determine whether neoadjuvant chemotherapy with Carboplatin and paclitaxel plus standard cisplatin-based chemoradiation with extended fields improves overall survival rates compared to standard therapy alone in women with cervical cancer with paraaortic lymph node involvement.

Secondary objectives will be to compare progression free survival, acute and long term toxicities, patterns of disease recurrence and patient quality of life between arms This is a phase III, multicenter, randomized, open label study, recruiting 310 patients during 4.5 years, with 3 years of follow up period.

Two groups will be compared : neoadjuvant chemotherapy with Carboplatin and paclitaxel plus standard cisplatin-based chemoradiation with extended fields, versus standard therapy alone.

Randomization will be stratified according to International federation of gynecology and obstetrics stages at diagnosis (IB1, IB2, IIA versus IIB-IVA), the size of positive para aortic lymphadenopathy and the number of node involved and will be balanced by blocks.

Women in the experimental arm will receive neoadjuvant chemotherapy with carboplatin and paclitaxel followed by standard therapy with extended field external radiation therapy and concomitant chemotherapy then intracavitary brachytherapy, alone or prior to surgery, depending on response to treatment according to the current guidelines.

Women in the control arm will receive standard therapy with extended field external radiation therapy and concomitant chemotherapy then brachytherapy, alone or prior to surgery, depending on response to treatment according to the current guidelines.

Follow up will be the same between arms. But in experimental arm, during treatment phase, a clinical examination and biological assessment will be performed before each cycle of neoadjuvant chemotherapy. Therefore, at the end of neoadjuvant treatment, just before standard treatment magnetic resonance imaging and positron emission tomography-computed tomography will be performed.

Then, all Participants will be followed every 4 months until 2 years after randomization and every 6 months during the third year according to current follow-up guideline for cervical cancer. Disease response and disease progression will be assessed using clinical examination. Quality of life will be estimated at baseline, at the end of neoadjuvant chemotherapy, before intracavitary brachytherapy and at each follow-up visit until 3 years after randomization.

Inclusion Criteria:

• Women with histologically proven invasive carcinoma of the uterine cervix and para aortic lymphadenopathy determined by either a positive positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro- D-glucose integrated with computed tomography or if negative positron emission tomography computed tomography based on histological examination of paraaortic lymph node dissection.
• Performance status Eastern Cooperative Oncology Group 0-2
• Stage International Federation of Gynecology and Obstetrics IB1 to IVA at diagnosis with para-aortic lymph node involvement
• Adenocarcinoma or squamous cell carcinoma or adenosquamous carcinoma
• Adequate renal function (creatinine clearance ≥60 mL/min)
• Adequate hepatic function (bilirubin <1.5 times normal and Serum Glutamooxaloacetate Transferase < 3 times normal)
• Adequate hematopoietic function Platelet count > 100x10 9/l and Absolute neutrophil count > 1.5X10 9/l)
• Written Informed consent for participation

Exclusion Criteria:

• Stage Federation of Gynecology and Obstetrics IVB at diagnosis
• Others histologies than adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma.
• Women who receive any prior chemotherapy for her cervical cancer
• Pregnant or lactating women
• Prior ( within the last 5 years) malignancies other than non-melanoma skin cancer
• Inadequate renal, hepatic or hematopoietic function (Cf previously)
• Cardiovascular pathology New York Heart Association II or more
• Pre-existing Peripheral neuropathy Common toxicity Criteria grade ≥ 2