PAROLA

Disease Free Survival (DFS) defined as the time from randomization until first relapse (local, regional, or distant), or death from any cause.

– Arm A (control arm): Standard chemo-radiotherapy and brachytherapy according to EMBRACE II and ESGO/ESTRO recommendations.
– Arm B (experimental arm): Pretherapeutic para-aortic lymphadenectomy followed by tailored chemo-radiotherapy and brachytherapy.

1. Age ≥ 18 years at time of study entry.
2. Newly diagnosed histologically proven cervical squamous carcinoma, adenocarcinoma, or adenosquamous tumor.
3. FIGO stage IIIC1 (FIGO 2018) cervical cancer with FDG-PET/CT showing FDG-positive pelvic nodes and FDG-negative PALN including equivocal lymph nodes in the common iliac and para-aortic regions. The highest positive lymph node must be located inferior to the common iliac bifurcation in both sides (anatomical level 1).
4. Patients with TNM T stage I-IIIB.
5. FIGO stage IIIC1 cervical cancer by positive pelvic sentinel lymph node from surgical staging (either intraoperative assessment (frozen section) or from final histology – patients are not eligible after radical hysterectomy, and FDG-negative common iliac of para-aortic lymph node on PET/CT (performed before or after SLN procedure).
6. Patient eligible for pelvic radiotherapy and cisplatin-based chemotherapy with a curative intent as confirmed by a multidisciplinary board.
7. ECOG performance status < 2 i.e. 0 or 1.
8. Life expectancy more than 12 months.
9. Pretherapeutic imaging FDG-PET/CT images should be available for central review.
10. Prior validation of the surgeon’s participation in the study by the Quality Assurance Comity.
11. Women should be post-menopaused or willing to accept the use of an effective contraceptive regimen during the treatment period. All non-menopaused women should have a negative pregnancy test within 72 hours prior to study entry.
12. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
13. Patient participating to other clinical trials including immunotherapy strategies or adjuvant chemotherapy is also eligible for the study. Adjuvant treatment must be decided prior to randomization.
14. Signed informed consent.
15. Patient affiliated to a Social Health Insurance in France (French patients only).

1. Unequivocal positive common iliac or para-aortic lymph nodes at pretherapeutic imaging FDG-PET/CT.
2. Negative or equivocal pelvic lymph nodes at pretherapeutic imaging FDG-PET/CT.
3. Metastatic disease confirmed by FDG-PET/CT.
4. Other histologies than adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma.
5. Contraindication for cisplatin-based chemotherapy.
6. Women who received any prior treatment for cervical cancer.
7. Prior surgery for the cervical cancer, except for cone procedure and pelvic lymph node staging.
8. Previous pelvic radiotherapy.
9. History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease after 5 years, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, adequately treated carcinoma in situ (any location) without evidence of disease.
10. Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure.
11. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice).

Lancement de l’étude : Décembre 2023
Fin estimée des inclusions : Décembre 2031
Nombre de patients à inclure : 510

Dr Alejandra MARTINEZ

Institut Claudius Regaud – CLCC Toulouse

Institut Claudius Regaud – CLCC Toulouse