BPH: Clinical Heterogeneity

It is clear from clinical trials of medications for BPH that personalized therapies will be needed due to the highly variable responses. Typically, patients complaining of lower urinary tract symptoms are placed on an alpha-adrenergic receptor blocker as a first line therapy due to its fast-acting relief of symptoms. These drugs relieve smooth muscle tone and are most effective in patients with early stage disease displaying a high smooth muscle to epithelial tissue composition. However, as the prostate enlarges, epithelial nodules predominate the tissue decreasing the likelihood of alpha-blocker efficacy.

The second-line therapy for BPH is a 5 alpha reductase inhibitor (5ARI), which induces epithelial apoptosis by decreasing the levels of intra-prostatic dihyrotestosterone (DHT). This therapy is effective at reducing prostate size by 25 percent in most patients.

Importantly, either therapy only reduces symptomatic progression by 34 percent, suggesting androgen-independent mechanisms of prostate growth and symptoms need to be targeted. Responses to current drugs are further reduced in patients with obesity, diabetes, and dyslipidemia.

These data suggest that there are further measures that are necessary for every patient, and completely novel measures necessary for individual patients. Our goal is to characterize the cellular composition of particular phenotypes, and more deeply understand the molecular changes driving these phenotypes. We use a combination of single cell RNA sequencing, flow cytometry, and immunohistochemistry on specimens from young organ donors and older men with prostatic enlargement.