What do patients with Peyronie's disease expect from therapy? A prospective multi‐center study

Little is known about patients’ pre‐treatment expectations in Peyronie's disease (PD).


INTRODUCTION
Peyronie's disease (PD) is an acquired chronic connective tissue disorder of the penile tunica albuginea, and may cause penile pain and plaque formation, as well as deformity, curvature, and length loss of the penis. 1,2Consequently, PD patients may have severe impairment of sexual activity and satisfaction, and suffer from detrimental psychological sequelae, for example, depression, negative self-perceptions, and self-attitudes of sexuality, as well as emotional and relationship problems (3-5).Depending on the phase and the severity of the disease, as well as patients' preferences, the therapy of PD consists of non-surgical, that is, conservative, and surgical treatment options.
Conservative treatment options include oral medications, penile traction therapy, intralesional injections, extracorporal shock wave treatment, and multimodal treatment combining different conservative therapies. 2,6Surgical therapy, that is, penile corporoplasty with or without grafting, is the gold standard treatment for patients with severe PD, who have stable disease for three months, and allows for correction of penile curvature and deformity, but may have important side effects, including penile shortening, hypoesthesia, and erectile dysfunction (ED). 1,2In patients with concomitant severe ED, penile prosthesis surgery represents an accepted approach. 1,2tients' expectations of treatment are defined as "the positive and negative experiences a patient believes that they will have as a result of receiving treatment", and may be influenced by various aspects, for example, predetermined ideas, online medical content, or psychosocial factors. 7As demonstrated in several studies, unrealistic pretreatment expectations may impair the process of the informed consent, jeopardize the physician-patient relationship, and result in medico-legal issues. 8Thus, a deeper understanding of patients' pre-treatment expectations may reduce barriers between patients and surgeons and improve treatment decision-making. 8Importantly, the position statement of the European Society of Sexual Medicine Against this backdrop, we aimed to provide a detailed evaluation of patients' pre-treatment expectations in PD.We hypothesized that patients undergoing surgery have more positive and more negative expectations compared to patients receiving the conservative therapy.

Patient cohort
The local ethics committee approved this prospective study (2021-

Patient evaluation and treatment decision-making
In both centers, the standardized pre-treatment patient evaluation included an in-depth history of onset and duration of PD-specific symptoms, prior PD-specific treatment and general medical history, as described previously. 5The age-adjusted Charlson comorbidity index (ACCI) was calculated, 9 to evaluate the comorbid conditions present in the patients.Auto-photographic documentation determined degree, direction, shape and severity of penile curvature, as described in detail previously. 10Physical examination and penile ultra-sonography determined location and size of plaques of the tunica albuginea of the penis.
In both centers, the standardized treatment decision-making corresponded largely to the recommendations of the Position Statement of the ESSM 1 and the EAU guidelines on Sexual and Reproductive Health. 2 In both centers, the modes of action of different conservative therapy options as well as the single steps of surgery were explained in detail to the patients in a standardized manner.In addition, the positive effects and potential side effects of different treatment options were thoroughly discussed with the patients in a standardized fashion in both centers, before a shared decision between patient and physician was made for a specific therapy.All patients underwent the recommended specific therapy.

2.3
Standardized, prospective assessment of patients' pre-treatment expectations, patient-reported psychological and physical symptoms, penile pain, symptom bother and erectile function Patients' pre-treatment expectations of therapy, patient-reported psychological and physical symptoms, penile pain, symptom bother and erectile function were assessed in a standardized fashion in both centers before starting the treatment.Following patient evaluation, counseling about positive effects and potential side effects of different treatment options, and shared treatment decision-making, patients were asked to complete a standardized questionnaire.The questionnaire included (a) the Stanford Expectations of Treatment Scale (SETS), 7 which allows a multidimensional assessment of patientreported positive and negative treatment outcome expectations.The six-items SETS includes two subscales, corresponding to positive and negative expectations, reaching total scores from 0 to 18, respectively.Lower and higher scores correspond to low and high levels of expectations, respectively.Finally, SETS includes two open-ended questions regarding patients' expectations of specific benefits and specific harms resulting from the recommended therapy.Patients' pretreatment expectations of conservative therapy and surgery, measured with SETS, were the primary end-point; (b) the Peyronie's disease questionnaire (PDQ) 11 ; and (c) the International Index of Erectile Function Erectile Function Domain (IIEF-EF). 12Patient-reported psychological and physical symptoms, penile pain, symptom bother and erectile function, measured with PDQ and IIEF-EF, were secondary end-points.

Statistical analyses
Our statistical analysis consisted of several steps.First, we performed descriptive analyses of clinical characteristics in patients stratified by the recommended treatment, that is, conservative therapy and surgery.
The distribution of frequencies and proportions of categorical variables across the groups was compared using the chi-squared or Fisher's exact test, as appropriate.The normal distribution of continuous variables was tested by the Kolmogorov-Smirnov and the Shapiro-Wilk test.Means and standard deviations (SD) were compared by Student's t-test and Mann-Whitney U-test, respectively.
Second, we calculated means of the positive and negative expectation scores of SETS with SD and stratified patients by the recommended treatment, that is, conservative therapy and surgery, to compare positive and negative expectation scores between the groups.
Similarly, means of PDQ subscale scores as well as the IIEF-EF score were calculated and compared between the groups.
Third, qualitative data of the answers to the open-ended questions were categorized through thematic analysis (grounded theory). 13In the first step, five authors (AS, LS, BW, VS, JFC) independently used half of the data to generate a framework with final themes.In the second step, the remaining data were used for internal validation.All authors approved the final themes.In the third step, the final themes were stratified by the recommended treatment, that is, conservative therapy and surgery, and graphically displayed using bar charts.
Fourth, we tested for correlations between SETS positive and negative expectation scores, respectively, and PDQ subscale scores as well as the IIEF-EF score using Spearman's rank correlation.The level of correlation was interpreted according to Cohen: |ρ| = 0.1, |ρ| = 0.3, and |ρ| = 0.5 corresponding to weak, moderate, and strong correlation, respectively. 14nally, multivariable linear regression analysis was performed to identify predictors of positive and negative pre-treatment expectations.
Reporting was performed according to the recommendations of the

Clinical characteristics
Clinical features are presented in Table

Patients' pre-treatment expectations
Patients undergoing surgery exhibited both higher positive and higher negative mean SETS expectations scores compared to patients receiving conservative therapy (all p < 0.001; Table 2).
Thematic analysis of patients' positive expectations revealed three major themes, including "straightening of the penis," "better sex life," and "stopping the disease progression" (Figure 1A).In addition, thematic analysis of patients' negative expectations revealed three major

F I G U R E 1
Themes of patients' positive pre-treatment expectations.
themes, including "erectile dysfunction," "side effects of treatment," and "incomplete straightening of the penis" (Figure 2A).Quantitative analysis revealed that the major themes differed significantly between patients undergoing surgery and conservative therapy: the most frequent major themes of positive and negative expectations in patients undergoing surgery represented "better sex life" and "erectile dysfunction", respectively.In patients receiving conservative therapy, the most frequent major themes of positive expectations represented "better sex life," "straightening of the penis," and "stopping the disease progression," whereas "side effects of treatment" and "incomplete straightening of the penis" represented the major themes of negative expectations (all p < 0.001; Figures 1B and 2B).

Patient-reported psychological and physical symptoms, penile pain, symptom bother, and erectile function
Patients undergoing surgery had higher mean PDQ symptom bother as well as psychological and physical symptoms scores, compared to F I G U R E 2 Themes of patients' negative pre-treatment expectations.patients receiving conservative therapy (all p ≤ 0.001; Table 3).There

DISCUSSION
To the best of our knowledge, the present multi-center study is the first to provide a prospective meticulous evaluation of patients' pretreatment expectations of the conservative therapy and surgery in PD.
7][18][19] We found that patients undergoing surgery had more positive and more negative expectations toward their treatment compared to their counterparts receiving conservative therapy.In addition, surgery was an independent predictor of positive and negative pre-treatment expectations.This confirms our hypothesis and corresponds to findings on pre-treatment expectations in other chronic diseases, which can be treated with either conservative therapy or surgery, for example, osteoarthritis. 20This may be attributable to the fact that PD patients undergoing surgery may differently cope with and presumably accept and adapt to a lesser extent to the consequences of their chronic disease, as shown in other diseases. 20Moreover, we found that patients undergoing surgery had different themes of positive and No ED 73 ( 23) 61 ( 28) 12 (17)   Abbreviations: ED, erectile dysfunction; IIEF-EF, International Index of Erectile Function Erectile Function Domain; PDQ, Peyronie's disease questionnaire; SD, standard deviation.Percentages may not add up to 100%, as they are rounded.
negative pre-treatment expectations, compared to patients receiving conservative therapy: "better sex life" represented the major theme of positive expectations in patients undergoing surgery, whereas "better sex life," "straightening of the penis," and "stopping the disease progression" comprised the co-major themes in patients receiving the conservative therapy.This may indicate that patients undergoing surgery do not necessarily expect to have a perfectly shaped and straight penis, but rather to be able having sexual intercourse again.In contrast, patients receiving the conservative therapy consider straightening of the penis as more important.In patients undergoing surgery, the major theme of negative expectations was "erectile dysfunction," whereas in patients receiving the conservative therapy, these major themes included "side effects of treatment" and "incomplete straightening of the penis."Importantly, some patients had unrealistic positive expectations, for example, "better psyche" and "happy partnership," and more patients receiving the conservative therapy, stated that they did not expect any negative pre-treatment expectations, in order to identify and eventually modify unrealistic expectations before starting the therapy.Thus, it can be ensured that a decision for a specific therapy does not rely on patients' misconceptions of benefits and harms of different treatment options. 21 found that patients undergoing surgery had more symptom bother as well as psychological and physical symptoms, compared to patients receiving the conservative therapy.To the best of our knowledge, no other studies have currently compared patient-reported symptom bother in PD treated with conservative therapy and surgery.
In contrast to the acute phase of PD, patients undergoing surgery have a different-chronic-disease phase, and this may contribute to a more pronounced symptom bother.In addition, more symptom bother as well as psychological and physical symptoms may be due to longer disease duration, different previous treatment attempts and patients' varying ability or willingness to adapt to and accept the PD-specific symptoms over time, as demonstrated in other chronic diseases, for example, chronic obstructive pulmonary disease or congestive heart failure. 22Last but not the least, the higher degree of the penile curvature in patients undergoing surgery may also be a reason for more symptom bother, as other authors have previously demonstrated that the more pronounced the penile curvature, the higher the PDQ symptom bother as well as psychological and physical symptoms scores. 16,23We found significant correlations between patients' negative expectations and symptom bother as well as psychological and physical symptoms, and a negative correlation between positive expectations and penile pain.Thus, these variables influence each other, and positive and negative treatment expectations may refer to diseaserelated symptoms. 24Again, these findings highlight the importance that clinicians evaluate pre-treatment expectations in patients with PD.
Despite the strength of our study, there are some limitations that merit attention.First, SETS was initially developed for pain research, 7 not for measuring pre-treatment expectations in PD.However, currently, there are few validated multidimensional instruments available for the evaluation of patients' expectations. 24In line with the expectancy theory, 25 SETS allows a multidimensional assessment of pre-treatment expectations, particularly with regard to negative and positive patients' expectations. 7In addition, SETS has been successfully implemented in other contexts, for example, smoking cessation trials, 26 due to its concise and uncomplicated design.Accordingly, the present study showed that SETS is a helpful tool, and we encourage its use the evaluation of pre-treatment expectations in PD.
Second, patients receiving different conservative therapies were combined in one group.In the majority of patients, the conservative therapy In contrast to the approach at the CeRA, corporoplasty does always include circumcision at the Department of Urology, University Medical Center Hamburg-Eppendorf.Thus, both groups, that is, patients undergoing conservative therapy and surgery, respectively, exhibit a certain heterogeneity, which may have influenced the results in the present study.In addition, none of the patients in the present study underwent penile prosthesis surgery.Therefore, it is of crucial importance that our study does not allow drawing conclusions regarding patients' expectations of penile prosthesis surgery in PD.Third, we were not able to evaluate patients who refused to participate in this study, which might have introduced an additional risk of bias.Finally, we did not analyze the impact of pre-treatment expectations on patient-reported outcome and satisfaction.Since patients' expectations do have effects on surgical outcome in other contexts, for example, bariatric, 27 cardiac and spine surgery, 28,29 we hope to report on this important issue in the near future.
In conclusion, patients with PD expect both more benefit and more harm from surgery compared to the conservative therapy.
In addition, patients undergoing surgery have distinct themes of pre-treatment expectations, compared to patients receiving the conservative therapy.Moreover, patients undergoing surgery have more symptom bother as well as psychological and physical symptoms.Finally, there is a correlation between pre-treatment expectations and patient-reported symptoms and bother.The findings of the present study allow deeper understanding of patients' pretreatment expectations in PD and underline the importance of assessing patients' expectations in clinical practice before starting the treatment.

(ESSM) 1
and the European Association of Urology (EAU) guidelines on Sexual and Reproductive Health 2 strongly recommend the evaluation of patients' expectations as a clinical principle.Yet, patients' expectations of conservative therapy and surgery remain undetermined in the current body of the literature.
was no difference in the IIEF-EF score between patients undergoing surgery and conservative therapy.There was a weak negative correlation between SETS positive expectation score and PDQ penile pain score (|ρ| = −0.15;p = 0.019), as well as weak positive correlations between SETS negative expectation score and PDQ symptom bother (|ρ| = 0.25; p < 0.001) as well as PDQ psychological and physical symptoms score, respectively (|ρ| = 0.21; p = 0.001).
effects of treatment or did not answer this open-ended question.Similarly, other authors have shown that a relevant number of patients, who were treated with different surgical techniques, had incorrect beliefs regarding the purpose of surgery in PD.For example, a retrospective study revealed that up to 18% of patients just expected plaque excision without caring about functional and cosmetic results.18Overall, the counseling of patients about the positive effects and potential side effects of different treatment options for PD in the present study led to realistic patients' pre-treatment expectations of the conservative therapy and surgery.However, some patients still had unrealistic positive expectations and a relevant proportion of patients did not expect any harm from treatment, although side effects have been discussed with all patients before starting conservative therapy or surgery.These findings highlight two pivotal things (a) the importance of thorough patient counseling on positive effects and potential side effects of different treatment options in PD, prior to a shared decision-making between patient and physician, in order to set realistic patients' pre-treatment expectations; (b) the importance of assessing patients' consisted of multimodal treatment combining different conservative therapies.Surgery consists of corporoplasty with grafting of Biodesign four-layer small intestinal submucosa (Cook Medical LLC, Bloomington, IN, USA) at the Department of Urology, University Medical Center Hamburg-Eppendorf, and grafting of TachoSil (Corza Health Inc., San Diego, CA, USA) at the CeRA, University Medical Center Muenster.
Clinical characteristics of 317 patients with Peyronie's disease undergoing conservative therapy and surgery.
TA B L E 1Abbreviations: ACCI, age-adjusted Charlson comorbidity index; ESWT, extracorporal shock wave therapy; PD, Peyronie's disease; PDE5i, phosphodiesterase type 5 inhibitor; SD, standard deviation.Percentages may not add up to 100%, as they are rounded.TA B L E 2Positive and negative pre-treatment expectations in 317 patients with Peyronie's disease undergoing conservative therapy and surgery.Abbreviations: SETS, Stanford Expectations of Treatment Scale; SD, standard deviation.
Patient reported psychological and physical symptoms, penile pain, symptom bother and erectile function in 317 patients with Peyronie's disease undergoing conservative therapy and surgery.
TA B L E 3