Extracorporeal Shock Wave Therapy for the Treatment of Chronic Pelvic Pain Syndrome in Males: A Randomised, Double-Blind, Placebo-Controlled Study.

[Nik]

This therapy looks very promising for symptom control for those who are not quite ready to remove their prostates. Has anybody had any experience with this and if so please share it with us?

[Arnon Krongrad, MD]

The paper attached above relates to 60 men with prostatitis of "at least 3 mo duration;" the article does not provide further information about median disease duration. In comparison to many other described cohorts, disease duration is relatively short. This is a group that should theoretically be relatively responsive to treatment.

As shown in Table 2, entry CPSI score was as low as 7. Pretty mild disease in some cases.

Treatment followup continues to 12 weeks. There are no data on further duration of symptom response.

The change in median CPSI is from 24 before to 20 after treatment (4 points).

For comparison, here are approximate CPSI changes with other treatments:

Quercetin 8 points
Pollen 7 points
Placebo 5 points
Aerobics 7 points
Acupuncture 10 points

Very promising? Perhaps in comparison with Lyrica, Ciprofloxacin, and Flomax, which don't work at all.

[Nik]

The CPSI reduction is not what impressed me about this study. A drop of 4 is no more than statistical noise to me.

What impressed me was the reduction in the VAS (Visual Analogue Scale) score, a proven method of measuring pain alone-for those who are not familiar. A drop of up to 50% was recorded after 4 and 12 weeks after treatment. To me a possible 50% reduction in pain alone is still very significant. This drop in pain alone can potentially be diluted by the overall CPSI, with all the other questions it asks, especially for those with severe urinary symptoms.

[Nik]

Imagine a man who scores 10 on question 4 of the CPSI. Lets say a treatment reduces his pain by 50% to 5. He experiences a lot of relief but his CPSI only drops by 5.

A man with a pain score of 6 who gets 50% pain relief to 3, only looses 3 points on the total CPSI.

This highlights the inadequacy of the CPSI in my opinion. I really think it needs to be revised. Still, I guess its all we have for now. A small proportion of men report impotence caused by prostatitis yet the CPSI does not include this parameter for these men, although I guess it could be partially absorbed by the quality of life score.

I personally would give much more points weighting to the pain section of the CPSI if I had any say in revising it. Pain is by far the most important problem with this condition. Pain is what ruins quality of life most of all.

[Arnon Krongrad, MD]

Let’s take a step back from the details and then return to them.

The trial attached above has strengths: Randomized, place-controlled, new type of treatment. These strengths make it interesting because they provide a level of comfort regarding the validity of the observations. The same was true of the recent Lyrica trial, which, like the trials of Cipro and Flomax, comfortably showed that treatment does not work.

What does the study show? Who are the patients? What are the implications?

First of all, we’re talking about what appears to be one of the least sick and least characterized of all reported prostatitis cohorts. The entry criterion of >3 months of illness is meager and begs a question: Is an illness of 3 months chronic? Is this what we’re talking about when we talk about chronic prostatitis?

Leaving aside semantics, there is a more practical issue: There is no indication of median illness duration. Was it 4 months, 10 years? Without knowing, how do we compare to other studies?

There is a related other issue: The report says little about previous treatments, other than that they had a “wide variety.” Fair enough, but variety is not the same as repetition. We may be dealing with patients whose median illness duration is 4 months and who each had ciprofloxacin, massage, pregabalin, and other varied treatments. But were these relative treatment virgins or hard-core repeat failures? Without knowing, how do we put the observations in context?

To put the merits of any treatment into perspective requires certain cohort descriptors because long-lasting illness and repeated treatment failures connote a much tougher disease. So if a new treatment works in the severely sick, it’s probably more effective than one that works only in patients who are only mildly sick.

In this sense, the report leaves us wondering how the study cohort compares with others and, by implication, how shock waves would fare in tougher, sicker cohorts. Consider the laparoscopic prostatectomy trial cohort, which is enrolling patients whose illness has endured from 1 year to 45 years, who have been ineffectively treated by as many as 20 doctors each with treatments as varied as trigger point release and prostate injections and months of antibiotics and spine surgery, and whose median CPSI is 35. Would shock waves also give the prostatectomy cohort a 4-point short-term change in CPSI? We cannot begin to infer because the shock wave cohort is minimally characterized.

Secondly, I am not a statistician but have spent lots of time around them and this has left me with questions. Why tabulate normality tests? This is unusual and feels like an over-compensation for lack of confidence. The use of off-the-shelf Sigma Stat further suggests a simplistic approach, in that no professional statistician I know uses this as his tool of choice. Given the numerous comparisons made, one has to ask if the proper controls were introduced to account for potential multiple-comparison penalties. This is not addressed. Speaking strictly for myself, the analytics leave me unsure about the statistical significance being reported.

As a tangent, let’s be clear about statistical significance. It is very rigidly defined to mean that an observation is not due to chance alone. In other words, a statistically significant observation may be due partly to chance. Nothing about statistical significance implies clinical significance. So as you ask, even if the right mathematical controls are proper, do patients find clinical significance in a 4-point drop in median CPSI? Patients care about clinical, not statistical significance, and these are different concepts.

Leaving research methodology aside ……..

Sure, pain is a central feature of this illness, but it is not the only feature. And yes, it’s perfectly fair to measure pain, including with a uni-dimensional index such as the Visual Analogue Scale (VAS). So how do we then compare the results of this study to those of others, including studies in which the CPSI showed more response than 4 points?

There appear to be precious few studies of prostatitis that report the VAS in action. A rare exception appears to be the 2005 validation of the Italian version of the CPSI, which is not a treatment study. So how do we put the shock wave VAS response into the perspective every patient has: Is this treatment better for me than the alternative? And if the VAS had a 50% response but this was not manifested in the CPSI, which measures some of the other dimensions of my illness and my quality of life, then what meaning does it even have?

As a corollary, is there really a man whose score on question 4 of the CPSI (“Which number best describes your AVERAGE pain or discomfort on the days that you had it, over the last week?”) drops from 10 to 5 but who has no response in any other question? Has anyone met such a person?

In comparing the VAS and CPSI responses, one has to remember that the CPSI actually has embedded into it several pain related questions (the question 4 cited above is a perfect illustration). In fact, the study of the Italian CPSI linked above showed that a VAS correlated very well with the pain component of the CPSI, so in the shock wave trial the VAS is most likely a redundant, not individually informative, measure. If there is a deficiency, and it’s not clear that there is one, it is in not analyzing the CPSI’s pain sub-score separately as has been done with other studies (see the UPOINT analysis as one example). It’s not the CPSI that would be deficient, but the analysis of its sub-scores.

Let’s examine the assertion that “pain is what ruins quality of life most of all” in the context of a drop in the VAS of 50% and a drop in the CPSI of 17% (which is a 4 point drop). The empirical observation would seem compatible with the assertion, even as it suggests that in this cohort there was more to prostatitis than just the pain dimension. This is not surprising.

Overall, we may want to be careful about over-analyzing any perceived mixed messages from this trial's IPSS, CPSI, and VAS. In fact, all of them trended down with shock waves. And yes, the VAS went down by 50%, but it’s a 3-point drop on a 10-point scale that correlates with the pain sub-score of the CPSI (the VAS is redundant with the CPSI, not additional to it). Overall, it seems that shock waves were associated with mild short-term symptomatic responses of urination, pain, and prostatitis, but not erections in a seemingly mildly ill cohort.

Yes, the CPSI has deficiencies. So while it captures pain, urinary dysfunction, and effect on quality of life, it omits the comorbidities that so many patients report: Chronic fatigue, irritable bowels, sexual and erectile dysfunction, social isolation. One has only to look at the video by Gerry to understand just how debilitating the fatigue and cognitive dysfunction can be and the video by David to understand just how sex can be disrupted by prostatitis. And how substantially they can be relieved by effectively treating the root cause of the symptoms.

Bottom line …..

At the end of the day, a patient asks which treatment is best for relieving his symptoms as fully, quickly, durably, and safely as possible. As he considers alternative approaches, even if he cares about pain but does not care at all about urination and sex and fatigue, he sees that he cannot use the VAS for the purpose of comparing. Today, this patient sees that he can only use the CPSI for standardized comparison. This is not so bad, in that the CPSI integrates a measure that correlates with the VAS and that is better representative of his illness.

As he surveys the available data and makes comparisons using the CPSI, he finds that in a cohort of what may have been relatively mild disease there was a median 4-point short-term response to shock waves. If his treatment objective is 4-point short-term response, then shock waves are a suitable treatment. So are acupuncture, aerobic exercise, trigger point release, and others.

[Jon]

I actually e-mailed one of the authors directly to get more information about shock wave therapy, and his research, but several months later have had no reply. Oh well.

By the way, I believe all the trials for tanezumab (including the trial for chronic prostatitis treatment) have been halted because of risk to patient safety.

[Arnon Krongrad, MD]

Great feedback. Thanks, Jon. If you do hear back about the shock waves, please let us know.

As for the Nerve Growth Factor antibody, tanezumab, we reviewed it on the Prostatitis Blog not long ago. There was a short post on an osteoarthritis study, which was completed, and another on NGF in prostatitis. Both are tangentially related posts.

FYI: Pfizer Halts Tanezumab Osteoarthritis Studies

[Nik]

John, I'm surprised you have not heard back from them, perhaps your email was lost in cyberspace? I got a very speedy response from Reinhold Zimmerman. Although the initial European study is over, which replicated the results from an original study in China, they are still doing follow up to see how long the relief has lasted. Reinhold Zimmerman is still in meetings with Curtis Nickel and Anthony Schaeffer (both prostatitis researchers) who are going to do their own trials on ESWT.

For what its worth there is a guy in Sweden who has found a lot of benefit with this therapy on the following forum:

http://www.chronicprostatitis.com/forum/viewtopic.php?f=4&t=604...

Just in case you have no login for this forum I have copied and pasted his post below:

"Here comes a little update on the ESWT treatment and how I am doing. I have now done my third session with ESWT.

The clinic is a private one and in located in a smaller town in Sweden. I have to travel there to have the treatment. They are currently evaluation this method for treating Prostatitis. They are only allowed to use the method against this Prostatitis syndrome, illness or whatever it is called. They are not using the method to treat trigger points, joint pain etc.

The first time I was examined by the urologist at the clinic. There where another urologist present at the examination. Don’t exactly know his role in the treatment. But he is somehow involved/or is checking up on this treatment. He is also one of the few in Sweden that carry on research about Prostatitis. Anyhow, during the examination they located where the pain comes from. I had no pain in the prostate itself, everything looked fine. But I had small pain in Levator ani and in the sinews, muscles and joints surrounding my rectum and the prostate.

I was able to do the treatment with ESWT at the first visit. The method is performed by a physiotherapist. She first examined me, and I showed her the spots where the pain comes from. Then she draws the mouthpiece of the ESWT-machine over these spots. She uses different power on different spots; she can’t go full power over spots with bones beneath and sensitive (the prostate) spots. Some spots hurts a lot, but not more then I can manage the pain. She always keeps checking up on how I was during the treatment. Sometimes she switches mouthpiece from a small one to a bigger one. The treatment is performed for around 45 minutes including checking up on how the last treatment has gone.

And the result? Amazing! After three treatments I’m doing very well, my overall pain has dramatically gone down. The trigger points in musculus gluteus and in the stomach have gone down. But mostly the pain when sitting has almost gone away; I can now sit down the whole day at work. But I am still standing at work; don’t want to irritate the spots down there unnecessarily. I had my first cycle tour for more than 1½ year this weekend. I have been out partying and drinking two weekends in a row. I have more energy and take on old projects in my apartment.

I have already decided to do one more session after the summer. I can’t say how much better I have become. Some days I feel 90% better and some days around 50% better.

I think the doctors are on something here. I have spoken to Hacksquat on the forum. It will be fun to see if he also signs up for the treatment. And what the results will be and what he thinks of it.

Ill keep you posted on how I feel after the two last sessions. But I am little busy catching up lost time :)."

It seems to me that although it may depend enormously on the individual receiving treatment, due to the non invasive and apparent lack of side effects it surely merits a try just to see for yourself. If it does nothing you can always have your LRP straight after.

[Arnon Krongrad, MD]

Thanks for sharing. It's always nice to see individual response. It helps us to gauge potential to relieve or fail to relieve in a way that population averages do not.So as this patient apparently got complete relief on the one hand, we see other individuals who even after 60 hours of treatment have absolutely no response. Individual patients looking at averages should remember just that: They are individuals, not averages, and we do not have mathematical formulas to precisely predict individual response. The best we cann offer today are probabilities.

It's interesting. He makes it sound like exercise and trigger point release, which have been associated in othere studies with average CPSI changes of approximately 7 and 6 points. What's different is that exercise and trigger point release protocols as published are multidimensional, involving everything from relaxation to range-of-motion exercises. The shock waves, which appear less effective than physical therapy and trigger point release protocols as published, are apparently uni-dimensional interventions.

It's important to keep in mind that there are different classes of chronic prostatitis severity. Shock waves therapy as publised in the paper linked above was apparently (see review of study weaknesses above) given to patients with mild illness: Short duration, average CPSI = 25, unknown number of treatment failures. Prostatectomy is a treatment offered as part of a clinical trial to patients with severe illness: Illness duration of up to 45 years, average CPSI = 35, up to 20 treatment failures. Let's not conflate shock wave "apples" with prostatectomy "oranges."

Given how poorly shock waves worked in this study of relatively mildly ill patients, the progression is surely not shock wave therapy failure and then prostatectomy, which is for relatively severely ill patients. There are many other approaches that have been shown to on average work better than shock waves' 4-point drop. For mildly ill patients, these are the treatments patients can consider after failing shock waves.

[Jon]

Hi, Nik.

I guess my e-mail just went into his trash or something. It was kind of him to reply to you so quickly.

There will always be treatments which somehow match a particular patient's needs. I started to take Lyrica after contacting a guy whose life was completely transformed by it. For him it was just what he needed. Unfortunately, it's done nothing for me. But I would have been foolish not to try. Likewise with the shock wave therapy. It's easy to try and probably not damaging, so if it becomes more widely available, I'll certainly give it a shot. In the case of the sufferer in Sweden, he got lucky and found something which was a perfect match for him. I'd like to know the severity of his condition, although the fact that he doesn't sit down at work may be an indication that it was quite severe.

[Nik]

Exactly what I thought Jon. I tend to think of anyone who has trouble sitting as a reasonably severe case. It would be nice to hear how he is doing though, as his last post was a few months ago.

Interestingly I started Lyrica after talking to a guy who had success with it (maybe the same guy you spoke to) and it was quite effective in the beginning. As the months went by though, its effects wore off. Perhaps my body, like that of an alcoholic with alcohol, started to build a tolerance to it!! It was already causing short term memory loss at the dose I started on so I did not want to increase the dosage.

Reinhold has offered to treat me in Austria where he works as per the trial, or there is an ESWT therapist in London who is looking at the trial at the moment to see if its something he is willing to try on me. As Dr K quite rightly notes, there are a lucky few who sometimes respond significantly above the average trial results, like the Swedish guy. In treatments where the side effects have shown minimal or absent, and the therapy is affordable and available, it seems worth a try.

I certainly wont be getting too exited about it though, and will report back anything of significance.

[Arnon Krongrad, MD]

These are the central parameters of informed treatment decision:

- Probability of effect
- Degree of effect
- Durability of effect
- Safety of treatment

As we all hear about the one patient who did great -- "uncle John had metastatic lung cancer but green tea cured him" -- an informed decision rests upon not anecdote, but research. Sure, Lyrica and shock waves and Mother Time are associated with symptomatic remission in individual cases. And individual cases (Dave Radford) are critical in helping us to generate hypotheses regarding treatment effect that can be tested in clinical trials (LRP for severe, treatment-resistant chronic prostatitis). Individual cases do not test these hypotheses.

An individual patient seeking informed decisions must go back to the medical literature. Which in this case shows that Lyrica is ineffective for chronic pelvic pain and that shock waves offer a short-term, 4-point average symptom score reduction in men who probably had mild disease. So this discussion has nicely helped us to differentiate a potentially idiosyncratic individual response from probability of response as measured in a population of pateints.

This discussion also has helped to differentiate mild illness from severe illness. Consider a man with 3 months of blood pressure of 135/95. And contrast him with a man with a 20-year history of blood pressure of 170/110. The men share the hypertension diagnosis, but the severity of their illnesses are different, the treatments are different, and the responses to treatment are different. We should not lump these two patients, just as we should not lump the shock-wave patients and the prostatectomy patients.

[silent.reader]

I have been tracking my CPSI for over a year now every other week or so and my scores are ranging from 24 to 38. So 4 point drop means nothing to me. I would surely try to insert a couple of electrodes in my butt as long as I don't have to go to Sweden for that.