Principles and applications of cross-sectional, case-control and cohort studies in gynecologic oncology: from classical observational designs to target trial emulation.

Observational research plays an important role in gynecologic oncology. Purposes of such studies include, but are not limited to, examining disease etiology, quantifying disease burden, identifying risk or protective factors, and evaluating the effectiveness and safety of pharmacotherapies and non-pharmaceutical interventions. Building on fundamental principles of observational study design, this article systematically introduces the basic concepts, key design considerations, and main strengths and limitations of three classic study designs: cross-sectional, case-control, and cohort studies in gynecologic oncology, supported by customized, practical examples. Based on the target trial emulation framework, we further elaborate on approaches to addressing common methodological challenges, such as immortal time bias, selection bias, and time-dependent confounding. Finally, we provide concise guidelines for the selection of study design for different research questions, with illustrative examples. This article aims to equip researchers in gynecologic oncology with the most readily useful and up-to-date set of epidemiological tools, thereby promoting broader and more appropriate use of real-world data to generate scientific and clinical evidence in gynecologic oncology.