***Trost Commentary and Key Take-Home Points***
This was a summary that Matt, Larry, Giorgio and I worked on to help other physicians better understand the Peyronie’s scientific literature. There are many challenges that come with trying to interpret Peyronie’s studies, and because of this, it is often important to critically evaluate any paper that is published in this area. As an example, nearly every oral therapy(vitamin E, potaba, colchicine, l-arginine, PDE5s, pentoxifylline, etc., etc.) which has been described for PD has some paper which reports significant improvements in some aspect of Peyronie’s Disease. However, nearly all of these studies were done without a control group, included small numbers of patients, did not classify patients as being in the acute or chronic phase of disease, were single centers, and used non-standardized ways of assessing outcomes.When follow-up studies are performed in many of these cases, they fail to demonstrate similar improvements. Therefore, being critical of any study which is published is really important in order to better sift through the snake oil treatments versus truly effective therapies.
Peyronie’s disease is a penile disorder characterized by fibrotic plaques that form in the tunica albuginea causing penile pain, curvature and sexual dysfunction. Roughly 0.4-13% of men are affected by the disease and while the etiology is unknown, penile trauma and genetics is thought to play a role in its appearance.Historically, many treatments have been used with varying degrees of success. A review of Peyronie’s disease literature was done in 2009 by Muller and Mulhall and found that found substantial limitations in many studies, challenging their reliability. Since then, EuropeanAssociation of Urology, American Urological Association and Canadian Urological Association have published guidelines for the management of Peyronie’s disease in an effort to encourage an evidence-based treatment approach.In an attempt to improve the way Peyronie’s disease is studied and researched, this paper highlights various aspects of high-level studies including patient assessment and treatment outcomes, study design and statistical analysis. This is done in hopes of increasing the scientific rigor with which Peyronie’s disease is studied.
Penile curvature is the most common symptom of Peyronie’s disease and is caused by plaque formation in the tunica albuginea. Measuring curvature only in degrees is not sufficient information, as there are other differences in deformity, such as sharp angles or more broad “crescent-type” deformities. Additionally, many studies perform the measurement differently. Some are done by patient estimation, using photography (either in-office or at home) or the provider may assess the curvature. The most accurate way to measure curvature is for a provider to perform an in-office goniometric estimate after achieving a medically-induced erection. Even in this manner, significant differences in measurement can occur based on provider placement of the goniometer angle, even up to 10-20 degree differences.
This is further complicated with complex curvatures such as biplanar deformities. When there are both primary and secondary curvatures, which can be combined into a “compound” curvature, many studies do not define which type of curve their data is based on. Curvature measurements can also be less reliable because of the variability in sexual dysfunction caused by curvature.
Penile girth, or “volume loss” deformities, is often reported in many studies, but lacks any standardized method of measurement. Terms describing girth can be inconsistent and methods of measurement vary greatly and can be difficult to reproduce. Since treatment makes such small differences (millimeters), any study claiming improvements in girth should be evaluated skeptically.
Penile length loss is also a very common complaint among men with Peyronie’s disease and is measured and treated in many studies. However, there is a wide variety of measurement techniques and methods used. Length measurements can be obtained in the flaccid, erect or stretched position, with stretched coronal length being likely the best measure. No matter the position used, there can be variability in exactly where the measurements are taken.
Data between stretched and erect measurements are conflicting where some show correlations and others that stretched penile length can underestimate erect length by up to 30%. Measuring an erect penis can also vary widely, as changes in pre- and post-treatment measurements could be due to decrease in curvature, where length was not actually gained.
Imaging is used as a supplemental assessment for curvature and is usually done using penile duplex Doppler ultrasound (PDDU). MRIs are sometimes used to differentiate penile plaques from other penile masses and helps identify inflammation. PDDU methods and techniques also vary by provider, causing differences in measurements. These variances can exist in the machine model, operator, erection quality, injection agent and amount, location of the probe and measurement angle. Its main use is to identify whether or not the plaque is calcified to help select appropriate treatment options.
While many questionnaires exist, only a few are standardized and validated for use on men with Peyronie’s disease. The Peyronie’s Disease Questionnaire (PDQ) was designed to quantify psychosocial outcomes related to treatment by measuring outcomes in 3 domains: psycological and physical symptoms, penile pain and symptom bother. The International Index of Erectile Function (IIEF) is also routinely used in Peyronie’s disease research. Both of these are limited in their requirement to engage in sexual intercourse within 1-3 months prior.
Classification of Study
Common classifications include randomized controlled trials (RCTs), prospective cohort (PC) studies, case-control (CC; retrospective) studies and case series (CS). RCTs are experimental, while the rest are observational. For RCTs, a control is essential for a study on Peyronie’sdisease, since some cases naturally experience improvement and placebo effects can be reported as successful.
Several important factors are determined by the study population, including population size,demographics, disease stage and characteristics. Larger study populations are more reliable and are attributed a higher level of evidence than small study populations. Comorbidities and demographics can skew results if the population is older or has comorbidities that can lead to further complications. The stage of the disease at time of treatment is an important factor, as different treatments will have varying success as the disease progresses. Certain disease characteristics such as plaque calcification, curvature severity, location of curvature and certain deformities can change the treatment efficacy.
Hypothesis, End points, and Defining Success
It is vital to select end points that support the hypothesis and are measurable with sufficient study power. Success should be standardized and clearly defined. Additionally, all clinical trials should be registered with the FDA, which will help ensure the study is reliable and unadjusted.
For an effective study, a detailed statistical plan should be used from the beginning of the project. This will include a thorough power analysis, which determines the sample size necessary for reliable conclusions. A power analysis includes factors such as sample size, statistical significance, treatment effect and standard deviation.
There is a lack of academic rigor in many studies and many potential points of deviation. It is necessary for specialists to work together to develop study protocols and outcome assessment tools to address limitations in future studies.
“Peyronie’s Disease Intervention Studies: An Exploration of Modern-Era Challenges in Study Design and Evaluating Treatment Outcomes” Ziegelmann, Matthew J. et al.
The Journal of Sexual Medicine, Volume 17, Issue 3, 364 – 377