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November 5-6, 1998

Workshop on Chronic Prostatitis Treatment Strategies

Treatment Reports
About this page:
In the mid-part of the meeting, researchers presented their work with prostatitis patients. Their reports are summarized here. The meeting was open to comments, so at some points, members of the meeting interrupted the speakers for comments.
The left column contains the name of the speaker. For complete titles, degrees, affiliation and contact information (E-mail and phone) click on the name or go to http://prostatitis.org/nihbase.html
Comments, Explanations and Notes appear in this type face. These are attributed to the webmaster .Direct quotes of the speaker appear in this type face.
For more information on how this page was made, click here.

Dr. Berger We call it Chronic Male Pelvic Pain Syndrome when we find no infectious or other known treatable cause. Scientifically, there is no known and treatable etiology (origin or cause) for CMPP, and no proven effective treatment. In practice, we see just about every kind of pain you can have. I feel that calling all of it prostatitis, is very 'prostatocentric' and prevents us from looking at the causes of the pain in ways that may be beneficial to the patient. If we get into controlled trials, there is a danger to lumping all men with pain together and therefore not showing that some appropriately defined subset of men may benefit. The location of the pain is important. We do a tender points survey, which we learned about from how patients are treated for fibromyalgia. Some people are sensitive to pain everywhere, and some have specific trigger points which can be treated. On occasion, we might try tender point local injections. Dr. Berger at this point stresses the links between IC [Interstitial Cystitis, a bladder-centered pelvic pain syndrome that mostly affects women] and Prostatitis Another example of sub-classifying men is interstitial cystitis. We have found that about 60% of men diagnosed with CMPPS or prostatitis have the bladder changes of interstitial cystitis. When we treat these men for interstitial cystitis they get better. Their response to therapy differs from those men without the bladder changes. We also found that men without the bladder changes of IC have more bacteria in their prostates and therefore may be more appropriately treated in controlled antibiotic trials. Putting all patients in a single trial may prevent us from seeing real differences in the effectiveness of therapy due to lack of study 'power" if we lump all patients together. In clinical trials, should we lump or split up patients? I believe that we should do more studies to sub-classify patients prior to beginning treatment studies. Currently response to therapy can only be used as a clue to the cause in any specific patient.

Dr. Feliciano We treat patients with:
A - Repetitive Prostate Drainage
B --Monitored Leukocyte Count
C -- Target specific Antimicrobials
It is fascinating that we cannot seem to solve this problem. Our treatments are based on the hypothesis of ascending infection. Patients usually have previous consults, diagnosis on symptoms alone, and have already been treated with antibiotics.
(Goes over patient histories.) We have to ask what are the risk factors to prostatitis. Assessing risk factors allow us to determine the harmful agents that came into contact with the susceptible host. A sub-clinical ascending infection is by far the most logical reason and possible triggering mechanism in the pathogenesis of CP.
"Why do antibiotics work only partially?" Perhaps the exact pathogen was never identified, a series of monitored prostatic drainage was not done and the regular sexual partner was ignored. Dr. Feliciano at this point advocates antibody, antigen and DNA detection of organisms in EPS, the fluid that can be pressed out of the prostate gland by the doctor's gloved finger.
We find that on the first drainage (very firm pushing with the doctor's finger) a look at Leukocyte levels often shows results below significant levels. But by the fourth drainage, almost all above the normal values.
Gives salutation in Tagalog: Salamat po!

Nickel We find that patients are demanding this kind of therapy. (Methods similar to Feliciano) We surveyed 7 major centers, we don't have such a clear picture of how widely massage is done in North America. Five out of 7 offer massage (Dr. Nickel did not say how often or anything about technique) , and several are investigating whether it offers any benefit.

Dr. Krieger I get two terms confused, 'irresponsible use,' and 'target specific.'
What's a normal EPS count? What's normal on the 5th day? (Discussion ensues, since nobody has done 4 or 5 'drainages" on 'normal' men...)

Dr. Feliciano On first drainage. What the data teaches us is that WBC rises because of the release of obstruction due to inflammation.

Dr. Krieger Might not another possible explanation be that if one took an asymptomatic man, and massage his prostate for 5 days, might not his WBC go up also?

Dr. Feliciano We have massaged asymptomatic men, we've seen the same pattern. I think they have prostatitis without symptoms. I have also seen cured patients a year later or many months later, and could not show high WBC.

Dr. Nickel Dr. Anderson(Dr. Rodney Anderson of the University of Maryland Baltimore Medical campus, who could not attend, but who is lead investigator for one of the NIH centers [see http://prostatitis.org/crn.html]) believes that there are massage trigger points in the perineum, he says it's not the prostate massage that does it (provides relief to patients) , it's the collateral massage of the perineum, and anus. Could you comment on that?

Dr. Feliciano I would doubt there would be other areas that are affected by drainage. This is what we do every day. The prostate is very distinct.

Dr. Kaplan The fact that antibiotics don't work, to me, indicates that the cause may not be bacteria. Is this a case of bacterial prostatitis that are misdiagnosed -- I feel it is not. Is it overtreated? Definitely. I see patients for second, or 12th opinion. I've studied 137 men. I'm trained as a urodynamicist, all I know is the urinary flow of the men I have studied is abnormal. Bladder outlet obstruction...is a small subset of these patients. What I see most is pelvic floor dysfunction. Ninety per cent the men I see are first-born males. We believe this is a very stress-related disorder. I can tell how stock market is going, because when it is down, I get more calls from my patients. I think we have to get off "curing" these patients, I think we need to think about healing these patients. Dr. Kaplan at this point looks at the age profile of chronic prostatitis patients, noting that they are a young group of patients. One symptom with pelvic floor, is testicular and scrotal pain. I think we really have to consider acupuncture, prostate massage, these things do have a role. (In answer to Nickel, who asked whether Dr. Kaplan may be seeing patients who are steered to him by the system because pelvic floor dysfunction is suspected) We may have a specific cohort. But to exclude this modality (from the study of prostatitis in general) is just as invalid (as leaving out any other theory.)

Dr. Moon This isn't an entity, it's entities plural, and our business is to make distinctions which it is.

Dr. Berger Most of our treatments now are just probes. Our treatments are just descriptive.

Dr. Doble In UK, the situation is similar to what you discuss, there are many ideas, but like practice in US, there is not a lot of science behind it. We don't use symptom questionnaires. Stamey (Stamey-Meares 4-jar test) we do not currently do as a routine in UK. If you don't use Stamey, then you can't compare results. Editors have continued to ignore papers written on symptoms alone, or antibody study, etc. It must be done if you're going to compare. We do TRUS as a routine, because it identifies tissue you can biopsy. Dr. Doble explains treatment in the UK, noting that doctors there mostly use antibiotic therapy, sometimes up to 3 months. We don't do TURP, because CP is mostly a disease of peripheral zone of the prostate gland, and even a radical turp leaves a lot of infection in place. In our analysis, the cause of inflammation seems more to be a persistent antigen rather than an auto-immune inflammation. We thought it was non-organismal, transported by urinary reflux. Correction of the reflux may be the most attainable goal and appropriate treatment. The reason urinary reflux affects peripheral zone is the ductal anatomy of the prostate gland. We do get results with allopurinol in high uric acid cases. In the future, we'd like to identify antigens, improve delivery of antimicrobials and anti-inflammatories, find some more prostate-specific anti-inflammatories, and also try to reduce urinary reflux.

Dr. Gushchin In Russian literature there is not agreement either. We find that prostatitis can affect somewhere between 30-40 per cent of all men at some point in their lives. Dr. Gushchin reviews russian literature and then explains about the patients he sees: Age is mostly in 21-50 years old.
Russian classification:
I Bacterial (specific or non-specific.)
II Non-bacterial prostatitis, allergic, congestive, and others.
III Prostatitis of mixed etiology
At the Moscow Institute of Urology....the symptoms and clinical signs match those in the West We do spectroscopic analysis of prostatic stones and find that they are 76 % non-organic components. (calcium compounds) Our study of metabolic disorders, ...may suggest calciuria as a background to stone formation.
Dr. Gushchin explains that there is a treatment at Moscow that is not used in the West. We do Magnetic Laser Therapy --it is a conservative treatment done on an out-patient basis over 10 to 14 sessions. Soft laser radiation has effects on the atomic and molecular level, leading to effects at the cellular level. (stimulates cell reproduction.) Stimulates immune response, analgesic, anti-inflammatory. Magnetic effect is used to intensify the effect of laser radiation. It really a very small device. It does not require anesthesia. One element is a transrectal probe, and the second is placed in thes suprapubic or perineal area. It is believed the depth of penetration of the radiation is 8 to 10 cm. On 106 patients, we have seen improvements in pain and voiding, as well as ejaculate. This device also can be used for laser acupuncture. (In response to a question) Our data have not been well controlled.

Dr. Johansen Dr. Johansen explains his role as having worked on a consensus prostatitis statement in Europe
We talked about the role of antibiotics in the treatment of chronic prostatitis. Soon we started to talk about classification and other unanswered issues in prostatitis. We decided to define it either as culture-positive or culture negative. There is much left to learn. I feel that the follow-up period is too short for a chronic disease, I'd prefer studies follow patients for at least one year. (Presents treatment algorithm based on Meares/Stamey test) I think that surgery has very little use in the treatment of prostatitis at all.

Dr. Krieger Dr. Krieger opened his remarks by asking the question: "To treat or not to treat?"
I have put together a lot of data that I've never published. I've been leery of publishing results that are not reproducible. I hope what we recommend can be truly useful. Data are incomplete. "To treat or not to treat," I think that's a good question. In men with asymptomatic prostatitis, they get a PSA test and that leads to a biopsy that shows prostatitis. Should we treat these patients? Should you treat white cells in the seminal fluid? For chronic prostatitis, there is no really validated treatment for 90 to 95 percent of patients. What's intellectually satisfying to me is to figure out what's wrong with these patients. Then we will know what to do. But, in the meanwhile, you have to do something for the patient, so there is a role for empiricism. We evaluate the urethra for white cells and pathogens using the best technology that we can, looking for chlamydia, and other pathogens, we use cultures, and PCR. We also do an ultrasound. I get a PSA and flow study. We do cystoscopy under anesthesia. We do studies on promising therapies, we've tried a few things;
*eliminate normal flora or skin contaminants;
*trying other antimicrobials;
*drugs for bladder outlet obstruction * dietary changes
* prostate massage therapy
(The results are plainly mixed as Dr. Krieger explains:) Bladder outlet obstruction; -- we didn't find this very much -- we might have had a different set of patients. (than Dr. Kaplan, see above)
But even within our institution there is selection bias on who sees what patients.
*Treating normal flora didn't result in long term changes in flora or in patient symptoms.
*Antimicrobials, insufficient insight. Nothing to write home about. Studies discouraging.
*Most patients don't have objective evidence of obstruction
*Dietary modification worked in a few patients
Overall, it has been disappointing, with less than a 25 per cent long term response.
Which raises an important question: what is the natural history of this disease. Many patients at some point choose the option of no further therapy. We did an anonymous survey, looked at 215 patients from 5 years, and found that sixty people, 28 per cent, were willing to complete the questionnaire after one mailing.
We discovered another question: What do we mean by untreated?
The things patients did, including changing to a more healthy diet, mediation, exercise, food supplements, hot baths, acupuncture. They took an unbelievable variety of food supplements. Before they saw us, everybody had been on antimicrobials, for long periods. After seeing us, only ten per cent took more antimicrobials. The outcome was that nobody was much worse or all better. Most were unchanged but 45 per cent were much better.
Conclusions:
*most patients remain symptomatic for long periods.
Dr. Krieger at this point cited what he called "The Hawthorn Effect," in which a business Gave workers more lights and saw the amount of work done in a factory increased. Gave even more lights, production increased more. Took out some of the lights, and work went up again. The point, Dr. Krieger said, was that if you pay attention to people, they perform better. Seeing patients can be beneficial.
I want to commend NIH, because of the need the randomized clinical trials. We must account for the natural history of CPPS (Chronic Prostatitis Pain Syndrome)

Dr. Moon The question I ask, is Treatment of What? We need to examine patients, actually collect some fluid. We have an obligation to promote that . My observation, or bias, is that in prostatitis patients who have obstructive symptoms. pain has not been an issue for them. Dr. Moon concludes that he proceeds to do what he can to lower pain without understanding the etiology of prostatitis.

Dr. Neal Dr. Neal did a double-blind study on Doxazosin, an Alpha Blocker (same class of drugs as Hytrin, Flomax and Cardura) The doxazosin group statistically improved, but as a group, the improvement was modest. For the patients that did show a response, there was good relief of symptoms. Clearly, some patients DO improve, but it is difficult to ascertain which patients that will be. It is extremely difficult to get prostatitis patients on a placebo.

Dr. Wiedner In studies of 656 men, we seldom found chronic bacterial prostatitis. It is truly a rare disease. Most of those were E-coli. Found Klebsiella and proteal species. In these patients, we try to eliminate bacteria and then eliminate inflammation.
In successfully treated patients, ph decreased, but in treatment failures, ph remained high. Antibiotic therapy gives patient new hope and they feel better. But there is questionable symptomatic response.

Dr. Nickel We ended up doing 3 radical prostatectomies of prostatitis patients, and on examining the tissues, we found infection throughout, uniform distribution.

Dr. Naber (Discusses whether pharmaceutical companies bringing out new antibiotics can or do perform adequate research on effectiveness of antibiotics in prostatitis.) There have been a lot of studies on the effectiveness of quinilones. But we still don't know what's really going on. We need to put pressure on the companies and FDA to get better research protocols. We need to have longer follow-up. I asked two companies to have a study including some patients who receive no antibiotics. There's a lot of effort put into these studies and we gain too little out of this.

Dr. Hochreiter Dr. Hochreiter reviews international research about transurethral microwave thermotherapy:
  • The few currently available clinical studies with small numbers of patients report a favorable outcome in terms of symptom relief after transurethral microwave thermotherapy
  • Perachino (Italy): microwave energy can destroy nervous fibers with possible effect of sensitive denervation and/or neuromodulation (relief of pain)
  • Sahin (New York): microwave energy has a bactericidal effect on bacteria which cause prostatitis
  • Conclusion: The knowledge about the role of microwave thermotherapy in the treatment of nonbacterial prostatitis is still poor. As the currently available data are promising further investigation in the use of this technology is required.

Dr. Jarvi We ask the question: Infection and infertility, is some infertility a form of asymptomatic prostatitis? There is evidence men with prostatitis have alterations in their sperm parameters. Either that or a decrease in sperm count. When we treat such men, fertility can improve. Up to 1/4 of men with infertility have some kind of infection. Less is known about infection in infertility than is known about prostatitis. But infertile men have higher rates of culturable organisms in the semen. What we often find is difficult-to-culture anaerobes. In men with infertility, if you try to get EPS, you won't have them in your office the next week. Due to dread of the DRE Up to half have mycoplasma, up to half have chlamydia, with anaerobes accounting for up to 90 per cent. We tend to treat both partners, because if there is an infection, it is most likely being passed back and forth. There is also the possibility of Non-culturable bacteria, or cryptic infection. Dr. Jarvi is asked what is the role of prostatic fluid in fertility. He replies that it is necessary for fertlity but admits that why it is necessary is not fully understood. Prostatitic fluid has a lot of proteolytic enzymes, breaks down the initial coagulum.

Dr. Schaeffer In our work we have found that chronic bacterial prostatitis is not very common, and when we do find it, there are usually no symptoms unless there is also bladder infection.
The most troublesome problem is actually recurrent cystitis.
We've been studying cytokines -- inflammatory mediators that may enhance or suppress inflammatory response. We've collaborated with people who work on arthritis. We looked at the cytokines TNF alpha and IL-1. There seems to be a trend towards elevated IL-1 beta in patients with Chronic Non-bacterial prostatitis. Same with TNF alpha, measured in EPS. In general we need to use as another parameter to help sort out these patients. One of our thought processes is, in addition to using white cells, we are using levels of cytokines.

Dr. Krieger Why these two cytokines and why not some others?

Dr. Schaeffer The reason why these two were picked were these are two most prominent. You cannot run a panel on everybody. We are not looking at other cytokines. But we appear to be learning some new things about these people. There are specific drugs against cytokines, and we are thinking of trying them.

Dr. Pontari Dr. Pontari repeated the assertion of other doctors who, lacking clear information on the cause, go after the symptoms. He uses Anticonvulsants such as Neurontin or Gabapentin. You have to go up slowly on dose because it is highly sedative. We are also using Ultram and Tizanidine --using more at night, because the main side effect is sedation. Anticonvulsants such as Neurontin have been used for treating neuropathic pain, and there may be some component of neuropathic pain in prostatitis. Tizanidine is an interesting drug because in addition to having central nervous system pain effects, it also reduces skeletal muscle spasm, such as would occur with pelvic floor muscles.

Dr. Potts We have found ureaplasma in symptomatic men, which responds to antibiotic therapy. Abnormal semen parameters, recently observed in this population, may be associated with subfertility. We did note that among symptomatic men with NEGATIVE cultures, however, that semen parameters were also abnormal, but not with the same magnitude. We think this organism is worth identifying and treating.

Dr. Rabon Dr. Rabon, a practitioner from South Carolina, surveyed 225 men and asked them what did you drive? We found that most of them drive pickups, forklifts, and over the road trucks. I divided them into groups. Gave antibiotic prescription plus cushion. Took two months to get better. Group using cushion only no antibiotics did even better.

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