Men with lower urinary tract symptoms (LUTS) represent a heterogeneous group, and treatment decisions are often based on severity of symptoms and physical examination findings. Identification of clinically meaningful subtypes could allow for more personalized care. This study advances phenotyping efforts from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) by adding data domains to previous phenotyping using urologic symptoms alone.
Two-hundred-seventeen LUTS, demographics, medical history, and physical examination datapoints from the LURN Observational Cohort study were assessed among 519 men with at least one bothersome LUTS, using weighted Tanimoto indices, semi-supervised learning, and resampling-based consensus clustering to identify distinct clusters of participants. Differentially abundant serum proteins of 220 men were compared across identified clusters.
Five refined male clusters (RM1-RM5) were identified. Two clusters reported mild LUTS (RM1: n = 66; RM2: n = 84). RM1 was older than RM2 (70.3 vs. 56.1 years), had more comorbidities (functional comorbidity index 2.4 vs. 1.5) and erectile dysfunction. Two benign prostatic hyperplasia-like symptom clusters were identified (RM3: n = 64; RM4: n = 188). RM3 has the largest postvoid residual volume (275 mL); RM4 reported more urinary frequency, urgency, urinary incontinence, pain, and psychosocial symptoms. RM5 (n = 119) was characterized by urgency urinary incontinence, frequency, and significant comorbidities and psychosocial symptoms. Fifteen (RM2) to 87 (RM1) differentially abundant proteins were identified within each cluster. Minimal overlap was observed between affected proteins and pathways across clusters.
Protein signatures across newly discovered subgroups suggest identified subtypes are biochemically distinct. Findings should be validated, but may represent populations with separate pathophysiology and therapeutic needs.
The LURN ClinicalTrials.gov Identifier is NCT02485808.
Neurourology and urodynamics. 2024 Oct 07 [Epub ahead of print]
Margaret E Helmuth, Abigail R Smith, Alexander P Glaser, Claire C Yang, Anne P Cameron, H Henry Lai, James W Griffith, J Eric Jelovsek, J Quentin Clemens, Brian T Helfand, Robert M Merion, Victor P Andreev, and the LURN Study Group
Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA., Northwestern Medicine, Feinberg School of Medicine, Chicago, Illinois, USA., Department of Endourology, NorthShore University Health System, Glenview, Illinois, USA., UW Medicine, University of Washington, Seattle, Washington, USA., Michigan Medicine Urology, University of Michigan, Ann Arbor, Michigan, USA., Department of Urology, Washington University in St. Louis, St. Louis, Missouri, USA., Duke Health, Duke University School of Medicine, Raleigh, North Carolina, USA., Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA.