CP/CPPS phenotypes may help target treatment

Although definitive answers will have to come from longitudinal studies, the statistics do provide intriguing clues-and a few unexpected ones.

Men who responded to treatment in two Chronic Prostatitis Collaborative Research Network trials-one for alfuzosin (Uroxatral) and one for pregabalin (Lyrica)-reported better quality of life, particularly physical quality of life, and better sexual functioning. They also tended to be older and have more prostatitis-specific pain, but less general pain. That may not be a surprise.

That's a head scratcher, but a recent study of dietary influences on CP/CPPS symptoms and preliminary evidence pointing toward allergic triggers in interstitial cystitis suggest some explanation and, possibly, research direction.

These factors and differences between the men with long-standing versus shorter-term disease argue for phenotyping men with the condition and targeting therapy-and research-accordingly, argued Dr. Nickel, who is working to extend and refine the phenotyping system for the chronic urologic pelvic pain conditions that he and Cleveland Clinic's Daniel Shoskes, MD, had recently proposed.

Predictable, unpredictable findings

The 272 men in the alfuzosin trial all had their diagnosis made within the previous 2 years and were relatively treatment naïve. The 321 men in the pregabalin trial, reported at this meeting, tended to have more chronic disease and had been heavily pre-treated.

As expected, based on entry criteria, men in the pregabalin trial who had more chronic, refractory disease were, on average, 7 years older, had had symptoms for about 9 years longer, and had had their diagnosis 7 years longer than the men in the alfuzosin trial. These men also had higher total Chronic Prostatitis Symptom Index scores, higher pain component scores, higher pain severity scores, and lower disease-specific quality of life. But, interestingly, there was no difference in the urinary subscore.

The men in that trial who had more chronic refractory symptoms also had more general pain, worse mental quality of life, and more anxiety and depression, but no difference in physical quality of life or sexual function from the other men in that trial. They also had significantly more urinary tract infections, psychiatric disease, cardiovascular disease, and neurologic disease, but no more respiratory allergic or gastrointestinal symptoms, endocrine or metabolic abnormalities, or infectious diseases than their counterparts.

On the other hand, in the pooled populations from the two trials, those who had had symptoms longer also had more urinary tract infections, gastrointestinal problems, endocrine or metabolic conditions, psychiatric conditions, or neurologic conditions.

Four conditions emerge

Comparing conditions in men between the two trials, four conditions emerged as significantly more prevalent in the men with more chronic, refractory disease: epididymitis, depression, anxiety/panic attack, and high cholesterol. This last finding puzzled researchers.

"Somebody can explain it to me, because I can't," Dr. Nickel quipped.

More robust databases on patient characteristics, he argued, "may allow prediction of risk of persistence of symptoms and response to therapy, suggesting that clinical phenotyping may be the key to understanding and managing CP/CPPS."

Session chair Philip Hanno, MD, MPH, of the University of Pennsylvania, Philadelphia, cautioned that there might be a sampling effect in trials, as patients who do get better are not entering clinical trials and only those experiencing the most severe symptoms will be included in trials. That argues for the longitudinal studies that are needed to reveal the true natural history of CP/CPPS and to point to the most successful treatments.