Neoadjuvant chemotherapy followed by radical surgery versus concurrent chemoradiotherapy in patients with FIGO stage IIB cervical cancer: the CSEM 006 study.

BACKGROUND: Concurrent chemoradiotherapy is the first-line treatment for FIGO stage IIB cervical cancer. Neoadjuvant chemotherapy followed by radical surgery may provide another treatment option. PRIMARY OBJECTIVE: To compare the therapeutic outcomes of neoadjuvant chemotherapy followed by surgery with cisplatin-based concurrent chemoradiotherapy for stage IIB cervical cancer. STUDY HYPOTHESIS: We hypothesize that the therapeutic effect of neoadjuvant chemotherapy combined with surgery and risk-adapted adjuvant treatment will be superior to that of concurrent chemoradiotherapy in stage IIB cervical cancer. TRIAL DESIGN: Patients with stage IIB cervical cancer will be randomized 1:1 to neoadjuvant chemotherapy followed by surgery (Arm A) or concurrent chemoradiotherapy (Arm B). In arm A, patients will receive three cycles of paclitaxel and cisplatin followed by a type C radical hysterectomy and pelvic ±paraaortic lymphadenectomy. Patients showing progression after neoadjuvant chemotherapy will be referred to concurrent chemoradiotherapy. Adjuvant therapy will be recommended according to the presence of pathological risks. In Arm B, all patients will receive definitive concurrent chemoradiotherapy, including external beam pelvic radiotherapy combined with concurrent weekly cisplatin followed by brachytherapy. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients between 18 and 60 years with histologically confirmed, untreated stage IIB cervical squamous carcinoma, adenocarcinoma, or adeno-squamous carcinoma. PRIMARY ENDPOINT: The primary endpoint is 2-year disease-free survival. SAMPLE SIZE: An estimated sample size of 240 is required to fulfill the study objectives. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: As of February 2020, 115 eligible patients from four institutions have been enrolled. Enrollment is expected to be completed by December 2022. TRIAL REGISTRATION NUMBER: ClinicalTrials. gov identifier: NCT02595554.

Sentinel lymph node biopsy versus pelvic lymphadenectomy in early-stage cervical cancer: a multi-center randomized trial (PHENIX/CSEM 010).

BACKGROUND: There is no accepted strategy for applying sentinel lymph node (SLN) biopsy as an alternative to pelvic lymphadenectomy in cervical cancer. It is unclear whether and when pelvic lymphadenectomy can be safely replaced by SLN biopsy alone. PRIMARY OBJECTIVE: To comprehensively compare the oncological outcomes of SLN biopsy with pelvic lymphadenectomy in patients with and without SLN metastasis. STUDY HYPOTHESIS: It is hypothesized that the oncological outcomes provided by SLN biopsy are non-inferior to those of pelvic lymphadenectomy in patients with clinically early-stage cervical cancer if risk-adapted adjuvant treatments are given. TRIAL DESIGN: All eligible patients will undergo SLN biopsy at the start of surgery. The resected SLNs will be submitted for frozen section examination. and patients will be triaged into the PHENIX-I (SLN-negative) or PHENIX-II (SLN-positive) cohort. In each cohort of this trial, patients will be randomized in a 1:1 ratio into the experimental (SLN biopsy alone) or reference (pelvic lymphadenectomy) arm. Radical hysterectomy will be performed for all patients, and adjuvant treatments will be planned according to post-operative pathological factors. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients aged between 18 and 65 years with histologically confirmed, untreated stage IA1 (lymphovascular space involvement), IA2, IB1, and IB2 cervical squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma. PRIMARY ENDPOINT: The primary endpoint is disease-free survival. SAMPLE SIZE: Estimated sample sizes of 830 and 250 are required to fulfill the study objectives of PHENIX-I and II, respectively. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: As of May 2020, more than 600 eligible patients have been enrolled. Enrollment is expected to be completed by December 2022, and presentation of results is expected in 2026. TRIAL REGISTRATION: NCT02642471.