Frailty Tied to Progression of Benign Prostatic Hyperplasia

By Lisa Rapaport

December 21, 2021

(Reuters Health) - Men with benign prostatic hyperplasia treated with drug therapy may experience more symptom progression and serious adverse events if they are frail, a recent study suggests.

The study was a secondary analysis of the Medical Therapy of Prostatic Symptoms trial, which was designed to compare the effect of treatment with doxazosin, finasteride, and combination therapy. The 3,047 men in the current analysis had moderate-to-severe lower urinary tract symptoms and reduced urinary flow rate. None had a history of hypotension, elevated prostate-specific antigen, or prior treatment for benign prostatic hyperplasia.

Baseline frailty was assessed using deficits identified with the 68-item Systolic Blood Pressure Intervention Trial frailty index, as well as deficits based on abnormal laboratory values. Total scores on the frailty index can range from 0 to 1, with scores of 0.25 or higher indicating frailty, scores of 0.25 to 0.1 indicating pre-frailty, and scores of less than 0.1 indicating that men were robust.

At baseline, 478 men (16%) had frailty and another 1,824 men (60%) had pre-frailty. Compared with robust men, clinical benign prostatic hyperplasia symptom progression was significantly more likely among me with pre-frailty (adjusted hazard ratio 1.36) and frailty (AHR 1.82), researchers reported in JAMA Network Open.

"The findings of this study supported our hypothesis that frailty is an independent predictor of lower urinary tract symptom progression," said study leader Dr. Scott Bauer of the University of California San Francisco and the San Francisco VA Medical Center.

"This is consistent with our growing understanding of common systemic and non-urologic causes of lower urinary tract symptoms in older men," Dr. Bauer said by email. "What was surprising is that this association was observed among men who clinicians suspected had symptoms specifically due to benign prostatic hyperplasia and therefore enrolled them in a benign prostatic hyperplasia drug trial."

The analysis used a composite endpoint to define clinical benign prostatic hyperplasia symptom progression, which included any of these things: lower urinary tract symptom progression; acute urinary retention; urinary incontinence; recurrent urinary tract infection or urosepsis, or an increase in serum creatinine attributable to benign prostatic hyperplasia of at least 1.5 mg/dl and to a value of at least 50% above baseline.

Overall, during a mean follow-up period of 4.0 years, the incidence of benign prostatic hyperplasia clinical progression per 100 person-years was 2.2 for robust men, 2.9 for pre-frail men, and 4.0 for frail men.

In addition, the risk of serious adverse events was significantly higher among frail (AHR 2.86) and pre-frail (AHR 1.81) men than among robust men.

One limitation of the trial is that it was conducted more than two decades ago, and included predominantly white men who were healthy enough to enroll. Results may therefore not be generalizable to men with multiple comorbidities or men from different racial or ethnic groups.

The mechanisms of this association between frailty and benign prostatic hyperplasia progression are also unknown and need to be investigated, Dr. Bauer said.

Furthermore, he and his colleagues wrote, "There is a critical need for diagnostic tests capable of distinguishing lower urinary tract symptoms due to BPH and bladder outlet obstruction vs frailty and other systemic causes."

"But in the meantime, clinicians should pause to reconsider frailty and other systemic age-related causes of lower urinary tract symptoms before referring older men for benign prostatic hyperplasia surgery when they have progressed despite maximal benign prostatic hyperplasia drug therapy," Dr. Bauer said. "Clinicians should also inform older frail men of their increased risk of adverse events and urinary symptom progression despite combination therapy and use shared decision making to ensure that the benefits outweigh the risks for each individual patient."

SOURCE: JAMA Network Open, online November 24, 2021.