- To define predictors of the deformity stabilisation and improvement in men with untreated Peyronie's disease (PD).
Peyronie's disease (PD) is an acquired, localised fibrotic disorder characterised by the deposition of collagen and fibrin in plaque on the tunica albuginea of the penis of unknown pathophysiology. It frequently results in penile deformity, penile pain, and erectile dysfunction [1-3]. Recent estimates on its prevalence vary from 3.2% to 8.9% [4, 5]. It has a significant negative impact on patient quality of life, with associated rates of significant depression of 48% .
Although Francois Gigot de La Peyronie provided some of the earliest published descriptions in 1743, there is a paucity of literature on the natural history of PD in the absence of medical or surgical therapies . An initial report from 1970 described a 50% spontaneous resolution rate of PD in 12 patients, with no patients demonstrating progression . Since then, using more rigorous follow-up and with larger patient populations, complete resolution rates of 3.2–13% have been reported [9, 10], along with progression rates of 30–48% [9, 11]. Further information about the natural history of PD in different patient populations, stratified by duration of symptoms at presentation is generally lacking, and is an important aspect of patient counselling. In the present study, we aimed to describe the predictors of PD deformity stabilisation and improvement in a cohort of prospectively enrolled patients opting against treatment for PD.
The study population consisted of patients (i) with PD, defined by the presence of a palpable plaque at presentation on examination by a urologist experienced with PD management, (ii) who had PD for <18 months (iii) who had uniplanar curvature (iv) who opted for no treatment (v) who underwent a formal in-office deformity assessment (DA) and had this repeated at least 12 months after the original DA, and (vi) who had at least 12 months follow-up. Patients were prospectively accrued over a 10- year period, and had demographic and PD data gathered in a retrospective fashion. The database was registered with the Institutional Review Board. The study population was then stratified into three groups based on their time to presentation for evaluation after the onset of symptoms: Group A, ≤6 months, Group B, 7–12 months, and Group C, 13–18 months. Stabilisation of deformity was defined as a change in curvature of ± 10° between DAs. Improvement or progression of deformity was defined as a ≥10° change between DAs.
DA was performed in the office by an experienced practitioner (J.P.M.) with the assistance of intracavernous injection of trimix (30 mg/mL papaverine, 1 mg/mL phentolamine, 10 μg/mL alprostadil), with repeat dosing given to a maximum of three doses until maximum erectile rigidity was achieved. Curvature was measured using a goniometer at maximum penile rigidity. On repeat DA, the practitioner was ‘blinded’ to the results of the initial DA. Duplex Doppler ultrasonography (US) of the penis was performed to assess for erectile haemodynamics as well as the presence of plaque calcification.
anova was used to define differences in stabilisation and progression rates between patient groups. Using logistic regression, multivariable analysis was used to define predictors of stabilisation and improvement. The model included: patient age, duration of PD, degree and direction of curvature, presence of penile pain and presence of calcification within the PD plaque.
In all, 176 men met all inclusion criteria and were included in this analysis. The mean (sd) age was 54 (27) years. The mean duration of PD before presentation was 9 (12) months. On initial DA, the mean (sd) curvature was 42 (27)°. The mean (sd) duration between the two DAs was 19 (7) months. Group A was comprised of 56 patients, with 84 patients in Group B and 36 patients in Group C. Patient characteristics according to time-to-presentation for evaluation are presented in Table 1. In all, 67% of the entire population had no change in deformity over time, while 12% improved with a mean (sd) change of 27 (14)° and in 21% the deformity progressed (worsened) with a mean (sd) change of 22(11)°.
|Group A||Group B||Group C||P|
|Number of patients||56||84||36||–|
|Patient age, years||47 (11)||52 (16)||58 (12)|| |
|Curvature, °||40 (20)||46 (16)||44 (19)||0.15|
|Time to presentation, months||2.8 (1.6)||8.2 (0.7)||14 (1.8)||–|
|Improvement of deformity||27||7||5||<0.01|
|Progression of deformity||30||23||0|| |
On multivariate analysis, predictors for stabilisation of deformity included a time-to-presentation of >6 months (odds ratio [OR] 2.4; 95% CI 1.8–3.9, P < 0.01), per decade increase in age (OR 1.5; 95% CI 1.1–2.8, P = 0.022), and age (r = 0.36, P = 0.018). Predictors of improvement of deformity included a time to presentation of ≤6 months (OR 4.1; 95% CI 1.4–7.2, P < 0.001), and per decade decrease in age (OR 2.1; 95% CI 1.3–5.5, P < 0.01).
In the management of patients presenting with PD, one of the most important aspects defining patient satisfaction before and after treatment is the extent of deformity. The fact that deformity becomes stable with time, generally beyond 1 year, is widely accepted. PD is divided into two phases, an acute (inflammatory) phase, where persistent penile pain and changes in deformity occur, and a chronic phase, where the deformity stabilises and pain resolves . Although there is some evidence supporting improvement in PD deformity with some therapeutic methods, there is an absence of randomised, double-blind, placebo-controlled trials supporting medical therapy [13-15]. Therefore, an understanding of the predictors of stabilisation of deformity and spontaneous improvement is of significant importance and will aid in the counselling of patients with PD.
Previous studies investigating the natural history of PD have investigated PD stabilisation rates, but have had methodological concerns, which potentially interfere with data interpretation. Gelbard et al.  reported on the history of PD in 97 men by means of a questionnaire study, with disease duration ranging from 3 months to 8 years. The authors found that 47% of men reported no change in their deformity, with resolution in 13% and progression in 40%. However, it should be noted that penile abnormality was never formally assessed by a physician, with progression being characterised by patient report.
Kadioglu et al.  have also reported characteristics from 307 men with PD, of whom 63 patients opted for no treatment and presented for follow-up. DA was performed after one intracavernous dose of papaverine to induce erection, and vacuum erection devices in those patients not responding to injection. The mean patient age in that population was 54.6 years, with a mean (sd) disease duration of 5.8 (2.7) months at initial presentation, and a follow-up of 8.4 (4.2) months. In that group, 67% of men had no change in deformity, 30% progressed and 3% reported complete improvement. It should be noted that despite a mean deformity of 30.8°, there was no report of partial improvement of curvature in this patient population even though a small minority of patients had complete resolution. These authors found that patients with progression were significantly younger (47.5 vs 62.7 years), were more likely to be ‘potent’ (defined by the authors as erectile rigidity adequate for penetrative intercourse), were more likely to respond to intracavernous papaverine and manual stimulation, and were more likely to have vascular risk factors. Methodological concerns centre mainly on the DA, as it is unclear how many patients responded to intracavernosal injection. Given that patients responding to intracavernosal papaverine were more likely to demonstrate progression of deformity, one questions whether the extent of curvature defined among patients requiring a vacuum erection device represented the patient's true extent of disease or was underestimating the deformity.
Mulhall et al.  have also described the natural history of PD in a population of patients presenting within 6 months of the onset of PD, who also opted against treatment and had a DA performed at baseline and at least 12 months after presentation. The mean patient age was 52 years, and the mean (sd) duration of PD at presentation in that group was 3.5 (1.5) months, with a mean follow-up DA occurring 14.5 months after the initial assessment. Among 217 patients with uniplanar or biplanar curvature, 12% had improvement, 40% had stable deformity and 41% worsened. While providing for general data as to the history of PD, this study was limited in that it did not analyse factors associated with the change in PD deformity, and did not consider time-to-presentation as a factor in describing the breakdown of deformity changes.
Finally, a recent study has described US characteristics as potential predictors of the natural history of PD . In the study, 95 patients were analysed, with a mean duration of PD at initial evaluation of 13 months, and a follow-up DA 12 months later. All patients underwent colour Doppler US. The patients were categorised into three groups based on the US characteristics of the PD plaque: group A patients had a solitary hyperechoic lesion without acoustic shadow (11 patients), group B had moderately hyperechoic, scattered calcified lesions with acoustic shadows (35) and group C had a dense calcified hyperechoic plaque with acoustic shadow (49). There was a reduction in the fibrotic lesions and curvature angle in 82% of patients in group A, while 34% of the patients in group B had a curvature reduction, and 8% of patients in group C had reduction in curvature. Although the authors conclude that US characteristics may be used to define the active vs the chronic phase of PD, no comparative statistical analysis is presented, making it difficult to draw conclusions from this data.
In the present population of patients presenting for evaluation of PD, those who had waited >6 months before presentation were twice as likely to have a stable deformity compared with patients seeking medical advice earlier in the course of their disease. In contrast, those patients presenting ≤6 months of the onset of symptoms were four-times as likely to demonstrate improvement, although the overall likelihood of improvement remained low. In all, 67% of men presenting for evaluation had stable disease on follow-up DA. Of note, improvement and progression of deformity rates tended to be similar within the patient groups described, indicating that those patients without presence of stable disease have similar likelihood of improvement or progression of deformity. In Group C, 95% of patients had a stable deformity, compared with 43% of those in Group A. This may be due to the fact that patients choosing to present late after the onset of symptoms may actually represent patients with generally stable disease soon after disease onset. We postulate that these patients may not have had rapid progression in the extent of curvature, and thus the onset of PD was not distressing enough to lead to prompt evaluation. This idea is potentially supported by the older age of the Group C patients compared with those in Group A. Although we do not have data to support this, it is possible that these older patients were in stable, long-term sexual relationships, leading to less embarrassment and thus removing a potential impetus for medical evaluation. Per decade increases in patient age were also associated with stability, whereas the likelihood of demonstrable improvement in curvature was significantly associated with per decade decrease in age. Degree and direction of curvature, presence of penile pain, and presence of calcification within the plaque on Doppler US were not associated with stabilisation or change in deformity. Of note, plaque calcification parameters as discussed above in the article by Bekos et al.  were not assessed in the present study.
The present study has some limitations. Although we present the largest series with relatively long follow-up for evaluating risk factors for PD stabilisation and improvement, the total population of 176 patients ultimately remains small and may limit extrapolability of the data. There remains an intrinsic error inherent to DA, as extent of deformity noted is directly correlated with erectile rigidity. While we think that a rigorous DA with repeat dosing of intracavernous medication until maximal erectile rigidity is obtained provides the highest likelihood of obtaining accurate results, it is possible that the full extent of deformity was not evaluated, therefore biasing the present results towards improvement of curvature. Additionally, the present study only evaluated patients presenting with uniplanar curvature, excluding multiplanar curvatures and other well-described deformities associated with PD (including hourglass deformities, indentations, and tapering). Given that our inclusion criteria required repeat DA, patients who did not present for a second DA were not analysed, introducing a potential bias in the present results. While the history of the disease may be similar in these patient populations, we cannot use this data to extrapolate results for other types of deformity.
In conclusion, among men with PD with a uniplanar curvature, PD deformity stabilisation is more likely among older patients and those with a time to initial presentation of >6 months, whereas improvement rates were higher among younger patients and those presenting to medical attention earlier than 6 months from symptom onset. Other deformity and disease characteristics were not associated with stabilisation or improvement in deformity. Along with more generic natural history data presented in the past, these data can be used to aid in patient counselling and to give the patient realistic expectations for the course of PD in the absence of treatment.