Planning and feasibility of phase III surgical trials in gynecologic oncology

Surgical randomized controlled trials (RCTs) have fundamentally reshaped gynecologic oncology, yet surgical interventions remain far less likely than medical therapies to be supported by prospective evidence. This disparity arises not from a deficit of scientific ambition or a scarcity of clinically meaningful surgical questions but rather from the methodological constraints intrinsic to surgical research: operative variability across institutions and surgeons, operator-dependent outcome heterogeneity, and the difficulty of standardizing complex intraoperative decision-making. This article, the first in a three-part series on surgical trials in gynecologic oncology, addresses the pre-trial phase, the period when a clinical question evolves into a rigorously justified, ethical, and feasible phase III trial. We examine five components of the trial planning process. First, we discuss equipoise, which refers to the genuine uncertainty among experts that must exist before a trial can be ethically justified, and this uncertainty gives shape and purpose to the trial design that follows. Second, we explore research questions which should precisely delineate the target population, clearly define the surgical intervention and comparator, and include a pre-specified primary endpoint that directly addresses the knowledge gap. Third, we distinguish between pilot and feasibility studies and argue that rigorous feasibility testing, including recruitment capacity, protocol adherence, regulatory infrastructure, randomization logistics, and surgeon credentialing, is foundational rather than optional. Third, we address the role of patient and stakeholder engagement, including the assessment of patient equipoise, the integration of patient-reported outcomes into endpoint selection, and the use of patient preference trial designs when strong a priori preferences exist. Fifth, we review the ethical and regulatory obligations unique to surgical trials, including the dual consent requirements for procedure and trial participation, and strategies for optimizing informed consent comprehension. These pre-trial decisions determine not only whether a surgical RCT can be launched, but whether it can be completed and ultimately transform care for patients with gynecologic malignancies.