Specific chronic prostatitis/chronic pelvic pain syndrome therapies may get help from phenotyping

May 15, 2010

In diagnosing and treating infection and inflammation, urologists increasingly are using approaches tailored to specific pathogens, patients, and clinical situations.

Key Points

Two posters dealing with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) highlight this trend. One shows that treatment with dutasteride (Avodart) over 4 years improves pain in older men with prostatitis-like pain and prostatitis-like syndrome, but did little for other symptoms.

"The problem I have with the field is, how do you know which patient is going to respond?" said Anthony J. Schaeffer, MD, professor and chairman of urology at the Northwestern University Feinberg School of Medicine, Chicago.

"CP/CPPS is very heterogeneous," Dr. Schaeffer explained. "If you give a bladder drug to a person with a bowel problem, it's not going to help. The concept of phenotyping is a more intelligent way of trying to determine what's going on."

To that end, another study shows that in mice and men, mast cells in the prostate can induce pelvic pain by releasing histamines. This study shows that in some men with CP/CPPS, the prostate is indeed to blame, said Dr. Schaeffer.

"It doesn't mean that all men with CP/CPPS have prostate problems that lead to their pain," Dr. Schaeffer said; bladder or bowel problems could also be to blame. But if a man with CP/CPPS has a prostate problem related to mast cells, clinicians could use more directed therapy, like antihistamines, to try to relieve his pain. Indeed, therapies targeting mast cell activation appeared efficacious for study mice with induced pelvic pain.

Somewhat similarly, another study shows that urine cultures do not necessarily reveal the pathogen responsible for associated urinary stone infections, or even whether the stones are infected.

"The supposition that the urine is always a reflection of what's going on in the urinary tract, or in this case the stone, is not always true," Dr. Schaeffer said.

Confronting bacterial resistance

Additional research reflects a continued recognition of the problem of bacterial resistance and growing recognition of its pervasiveness, Dr. Schaeffer said. However, he said most of these abstracts "emphasize the big picture but don't help the clinician." One such study detailed increasing Escherichia coli resistance patterns among first-line antibiotics in uncomplicated, community-acquired urinary tract infections.

"That just tells us there's a problem. It doesn't say what we should do about it," he said.

Conversely, another research team used data mining techniques to show that microbes' susceptibility to various treatments is very site specific and can even depend on which clinic one analyzes within a given facility.

Among patients of the outpatient urology clinic studied, sensitivity to nitrofurantoin (Furadantin, Macrobid, Macrodantin) held steady over several years, while sensitivity to ciprofloxacin (Cipro, Proquin XR) and trimethoprim-sulfamethoxazole (TMP-SMX [Bactrim, Septra]) declined. Moreover, the key factor in this study for improving empiric antibiotic performance was a history of antimicrobial resistance.

"The more resistant organisms tended to be in patients treated at the urology clinic," Dr. Schaeffer said, adding that this result occurred not by chance, but because the type of patients referred to urologists generally have more complex issues.

Armed with such information, "We can at least begin to be more thoughtful in our selection of empiric therapy," Dr. Schaeffer said. The take-home message is to be very cognizant of environment and patient type, he added.

Therefore, Dr. Schaeffer notes that presentations at the AUA meeting should not only raise awareness of the resistance issue, but also give urologists new insights into what might cause infections.

"Hopefully, they [clinicians] will be able to be more precise in their diagnosis and treatment of people with infections and pain than they used to be," Dr. Schaeffer said. "The concept that bugs, men, and infections are all created equal is clearly not true. We must realize there's a very heterogeneous group of individuals, bugs, and scenarios."

To improve outcomes, urologists must coordinate the diagnosing of clinical entities, phenotyping of patients, and tailoring of treatments with each clinical situation, he says. In 3 to 5 years, he predicts that urologists will have a better understanding of all these factors, thanks partly to epidemiologic and basic science research into pain syndromes now under way at the National Institutes of Health.

"The future of medicine is going to be goal-directed therapies," Dr. Schaeffer said. "You can't just give one pain medicine and expect it to help everybody."