Phase III clinical trials of radical hysterectomy with minimal parametrectomy for patients with early-stage cervical cancer: a review

Abstract

The standard surgery for patients with International Federation Gynecology and Obstetrics (FIGO) stage IB–II cervical cancer is a Piver-Rutledge-Smith class III radical hysterectomy with pelvic lymphadenectomy involving a wide resection of parametrial and paravaginal tissue to control parametrial involvement. However, adverse events can occur such as severe long-term neurogenic bladder due to parametrectomy. This review evaluates ongoing and completed phase III clinical trials of less radical hysterectomy with regard to parametrectomy. The PubMed database, Clinical Trials.gov, and Cochrane Central Register of Controlled Trials were used to extract information on two completed and four ongoing clinical trials. Less radical surgery led to similar oncologic outcomes to standard surgery in two phase III randomized controlled trials (Piver class II vs. class III, and class I vs. class III radical hysterectomy with pelvic lymphadenectomy). Less radical surgery also led to fewer complications, including urologic morbidity; however, more than 50% of patients received radiotherapy following such surgery, and showed higher morbidity rates because their enrolment was due to the presence of a large tumor (>4 cm). Three phase III randomized controlled trials and a phase III nonrandomized confirmatory trial are presently ongoing. Major inclusion criteria include FIGO stage IA, IB, or IIA1, a mainly ≤2-cm tumor, limited depth of stromal invasion, and/or no lymph node metastasis. Surgery for the standard arm is a class II or class III radical hysterectomy, and the experimental surgery is a simple extrafascial hysterectomy or class II radical hysterectomy. Primary endpoints are overall, disease-free, or recurrence-free survival. Although primary endpoints, eligibilities or types of radical hysterectomy differ between trials, if noninferiority in overall, disease-free or recurrence-free survival is observed in any trial, new standard, less radical, curative hysterectomy may be established for early-stage, small-sized, invasive, cervical cancer.