LymphSens study: the enigma of subjective lymphoedema - how often and why do patients report lymphoedema after breast cancer treatment without an objective measurable swelling? The role of lymphatic and sensory processing problems: a protocol for a multicentre prospective longitudinal study.

introductionBreast cancer-related lymphoedema (BCRL) at the arm and/or trunk/breast is a highly feared complication following breast cancer treatment and can be objectified using the state-of-the-art criteria based on volume, extracellular water ratio or skin thickness measurements. Although the incidence of objective BCRL is decreasing due to advances in breast cancer treatment, many patients report a sensation of swelling without the presence of objective BCRL, referred to as subjective BCRL. As little is known about the prevalence and the transitions between different BCRL states (no-subjective-objective) over time, as well as about the underlying mechanisms and contributing factors of subjective BCRL, this will be investigated in the LymphSens study. METHODS AND ANALYSIS: 230 patients with a new diagnosis of unilateral breast cancer will be included in a multicentre longitudinal study. Measurements are performed from presurgery to 12 months postsurgery. The primary objective (aim 1) is to determine the prevalence rate of subjective and objective BCRL at 1, 6 and 12 month(s) postsurgery, as well as transitions between BCRL states (no-subjective-objective BCRL) by a multinomial logistic regression model with generalised estimating equations and transition matrices, respectively. A second objective (aim 2) is to determine factors related to four potential underlying mechanisms (lymphatic, nociceptive, neuropathic and central sensory processing problems) that contribute to the occurrence of subjective BCRL in comparison with no self-reported swelling and objective BCRL. As a third objective (aim 3), within the group of patients with subjective BCRL, we will determine factors related to these four underlying mechanisms that contribute to the severity of subjective BCRL. The analyses for aim 2 and aim 3 will be conducted both at specific time points, that is, 1, 6 and 12 month(s) postsurgery using exploratory analysis and across all time points collectively using multivariable binary logistic regression models or multivariable longitudinal models for repeated measures. ETHICS AND DISSEMINATION: The LymphSens study protocol received approval from the Ethics Committee of UZ Leuven (S68133) and UZ Antwerp/University of Antwerp (5676-003252). The results of the LymphSens study will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT06324721.