Background/Objectives: Pulsed electromagnetic field (PEMF) therapy involves the use of magnetic waveform energy for targeted treatment delivery. This technique has shown promising results in the treatment of various cancers. Currently, treatment of bladder cancer is highly invasive, involving intravesical chemotherapy or radical cystectomy. The potential therapeutic effects of PEMF therapy on bladder cancer are a relatively new and understudied area; therefore, the goal of this investigation was to gain mechanistic insight by examining the effects of PEMF therapy on a bladder cancer cell line in vitro. Methods: Cells from the bladder cancer cell line HT-1197 were cultured and incubated with (treatment group) or without (control group) PEMF therapy for one hour each day for five days. Cell counts were compared using Incucyte^® data to determine proliferation rates. At days 1 and 5, total RNA was isolated from cells, and following quantity and quality checks, gene expression was compared between the two groups. Proliferation rates from cell line HT-1197 were compared to prior published results on the bladder cancer cell line HT-1376. Results: HT-1197 cells treated with PEMF therapy had slower proliferation rates compared to controls (p < 0.05), but HT-1376 cells did not (p > 0.05). Principal component analysis showed complete separation of treated and untreated cells, with PEMF treatment accounting for 76% of the variation between the groups. Expression of numerous genes and cancer-related pathways was altered in the treated cells relative to the controls. Conclusions: Bladder cancer HT-1197 cells treated with PEMF therapy had slower proliferation and corresponding changes in gene expression. Several cancer-relevant pathways were differentially regulated following PEMF treatment. The conclusions are limited by the lack of a control healthy urothelial cell line in the experiments. Despite this shortcoming, our results suggest that PEMF therapy may be a promising avenue for further research in the treatment of bladder cancer.

In a previous study we reported that molecular profiling of bladder mucosal tissue from a modest number of IC/BPS patients resulted in a clear separation based on anesthetic bladder capacity (BC), with 400 cc representing the apparent breakpoint between low and non-low BC. The purpose of the current study was to revisit this earlier stratification finding, using a combination of molecular and clinical data, from a large and heterogeneous patient cohort. To provide an updated assessment of IC/BPS patient stratification based on anesthetic BC, whole genome gene expression data from 48 mucosal biopsy samples (41 IC/BPS patients; 7 controls) were analyzed with unsupervised clustering and principal component analysis (PCA) to identify primary clusters of patients. This identified three primary individual clusters: (1) IC/BPS patients with a BC between 200–500 cc (n=19), (2) IC/BPS patients with a BC of 501–1500 cc (n=22), and (3) controls. Next, complete demographic, clinical, and questionnaire data prospectively collected from an additional 450 patients from our patient registry were used to conduct a combined analysis to verify this relationship. Characteristics of all 491 IC/BPS patients were compared between those having the current low BC cutoff (≤ 400 cc) and the proposed new cutoff (500 cc) by utilizing independent samples t-test (continuous variables) and chi square tests (categorical variables; p ≤ 0.05 was considered significant). A statistical comparison of the demographic and clinical characteristics of the entire 491 IC/BPS patient cohort showed that those with a bladder capacity ≤ 500 cc were older, were more likely to have Hunner lesions, and had higher symptom scores. This group also had a lower average number of non-urologic associated symptoms, pelvic pain syndromes, and neurologic, immune, or systemic pain syndromes. By combining newly acquired molecular data with clinical and demographic characteristics in a large cohort of IC/BPS patients, we conclude that anesthetic BC ≤ 500 cc provides a clinically meaningful biomarker for the bladder centric IC/BPS phenotypic subgroup.