How to define success in prolactinoma treatment - a systematic review and theoretical framework.

Purpose: As consensus regarding outcome sets for prolactinoma treatment evaluation is lacking, outcome parameters reported in literature were evaluated, and objective, clinically relevant outcome sets were proposed.

Methods: A systematic review of studies up to February 2, 2024. Reported biochemical and radiological parameters, clinician-reported findings, patient-reported outcomes (PROs), and definitions of disease remission, control and recurrence were extracted and placed into clinical context. Subsequently, objective and clinically relevant definitions of clinical outcomes were proposed based on the findings, with comprehensive outcome sets to evaluate treatment success.

Results: 137 articles were included. Albeit ill-defined or subjective, 23 unique prolactin parameters, and 73 unique radiological parameters were reported. Seventy articles included clinician-reported findings, and none reported PROs. Ultimately, 27 unique definitions of remission, 3 unique definitions of disease control, and 20 unique definitions of recurrence were reported. We propose two separate definitions for biochemical and clinical remission/recurrence - either evaluating prolactin levels only, or including symptomology, gonadal function and radiology. Integrated outcome quadrants were illustrated to objectively categorize treatment success by combining achievement of treatment goals with occurrence of adverse effects. A three-tier outcome set based on the Value-Based Healthcare principles was provided.

Conclusions: Heterogeneity in reported outcome parameters using varying definitions hamper comparison of prolactinoma treatment outcomes. This study proposes objective, easily applicable, and clinically relevant definitions of clinical outcomes, and offers a comprehensive outcome set. These parameters enable comparison of outcomes across treatment modalities and medical centers to gain insight into this rare disease and improve prolactinoma care.