Trost, Landon

Abstract Introduction Limited data currently exist on the role and efficacy of additional series of collagenase clostridium histolyticum (CCH) injections among Peyronie’s disease (PD) men who have previously failed a first series of injections. We have previously published outcomes of men undergoing a novel protocol for CCH injections and which demonstrated significant improvements compared to original IMPRESS I and II techniques. We therefore sought to evaluate results of men who had previously failed CCH injections to determine if they would respond to a repeat course using a more aggressive protocol. Objective To evaluate outcomes of a novel protocol for CCH injections among men who had previously failed 6-8 CCH injections using a traditional approach. Methods A randomized, controlled trial (NCT05108558) is ongoing. All participants had previously failed to achieve ≥20% curvature improvement with 6-8 prior CCH injections. Men were randomized 3:1 to receive either CCH + traction (RestoreX) + sildenafil (treatment) up front or initial observation followed by treatment (controls). Outcomes were compared between treatment and control groups. Key measures included objective curve improvements and standardized/non-standardized questionnaires, with assessments obtained at baseline, 6-weeks after completion of CCH (treatment arm), after the no treatment period (controls), and at 1 year. Results A total of 22/40 men have been randomized to date, with 11 having fully completed treatment. Mean age was 64 years, with a median PD duration of 24 months. Mean composite baseline curvature was 80 degrees, with 55% having hourglass or indentation deformities, 10% calcification, median baseline IIEF-EFD 15, and 60% able to have penetrative intercourse. Median estimated improvement with the prior CCH series was 0% (IQR 0, 19.4), and the median number of prior injections was 8. The majority of men were dissatisfied with their prior series of CCH (60% vs 30% satisfied, 10% neutral). Of the 11 men who had completed the study protocol, 64% required 1 series, 9% 2 series, 18% 3 series, and 9% 4 series. Compared to the no treatment arm, treated men experienced significantly greater improvements (mean 78 degree vs 15, p=0.01). IIEF-EFD was also improved more in treated men (+4.3 vs -5.7, p<0.05). 100% of men reported a subjective major improvement in curvature, with the average subjectively estimated improvement 91%. 67% reported improved sensitivity (33% no change), while 60% reported improved or no change in erectile function, with 20% unsure, and 20% somewhat worse. Post-treatment, 83% of men were very satisfied with CCH as a treatment and 17% somewhat satisfied. Conclusions Repeating CCH using a novel protocol after an initially unsuccessful course of CCH achieves significant improvements in curvature and patient satisfaction. Additional data, including external validation, are warranted. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceuticals. Clarification: Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Matthew Ziegelmann - Endo Pharmaceuticals.

Abstract Introduction There has been significant ongoing debate on the role and utility of prednisone post-vasectomy reversal to improve sperm counts and long-term patency. However, there are relatively limited data available on the efficacy, with essentially no data available on pregnancy outcomes. Objective To report outcomes of randomized, clinical trial evaluating varying protocols for prednisone administration post vasectomy reversal. Methods A randomized, controlled trial was performed (NCT04788823) with an anticipated 100 men randomized to one of four prednisone protocols post vasectomy reversal: no treatment (Control), prednisone 20 mg taper over 1 month beginning the first month post-op and then every other month x 6 months (High Dose), prednisone 20 mg taper over 1 month if declining sperm counts or a 0 count were identified (PRN), and prednisone 5 mg daily x 1 week, followed by no treatment x 1 week, continued for 6 months (Low Dose). Randomization tables were created a priori to ensure an equal representation of differing durations of time since the original vasectomy as well as an equal distribution of VV/VV vs VV/EV vs EV/EV procedures. All men had semen analyses obtained monthly for a first 12 months. Surveys were sent periodically to follow-up on subsequent pregnancies. Inclusion criteria included having a female partner <36 years of age with no known fertility factors. Results A total of 75 men were ultimately enrolled due to interim findings suggesting inferiority of the High Dose and PRN treatment arms and decision to close those arms before completing full enrollment. Final enrollment included: Control (n=25), High Dose (n=14), PRN (n=11), and Low Dose (n=25). The mean patient age was 38.5 years, mean partner age 29.6, and mean time since vasectomy 6.3 years (SD 5.0). 82% of men underwent VV/VV, while 15% VV/EV, and 3% EV/EV. All men underwent successful anastomosis bilaterally with no cases of one-sided or no anastomosis performed. At a mean follow-up of 16.5 months (range 7.6 to 25.1), an overall patency (sperm observed on sample) rate of 93% was noted (Control 96%, High Dose 93%, PRN 100%, Low Dose 88%, p=0.41). The mean sperm concentration post-op was 34.4 million/ml (Control 24.0, High Dose 38.4, PRN 21.0, Low Dose 49.8, p=0.33). Patency rates at 6- and 12-months were: 6-months (Control 88%, High Dose 80%, PRN 83%, Low Dose 94%, p=0.75); 12-months (Control 75%, High Dose 71%, PRN 75%, Low Dose 91%). Mean sperm concentrations at 6- and 12-months were: 6-months (Control 15.7, High Dose 21.5, PRN 6.9, Low Dose 25.7, p=0.50); 12-months (Control 12.6 million/ml, High Dose 17.1, PRN 36.1, Low Dose 50.4, p=0.64) At the 6-month post-op time point, the overall rate of pregnancy was 47%, with notable differences between cohorts: Control 57%, High Dose 10%, PRN 38%, and Low Dose 67%, p=0.02. No patients discontinued prednisone due to side effects. Conclusions Prednisone taper protocols appear to reduce the likelihood for pregnancy following vasectomy reversal. Use of low-dose prednisone results in non-statistically higher rates of patency at 6- and 12-months, mean sperm concentration at 6- and 12-months, and pregnancy at 6-months. Overall results suggest superiority of either no prednisone post-vasectomy reversal or a low dose protocol but argue against the use of higher dosages at any time due to its negative impacts on pregnancy rates despite maintained sperm counts. Disclosure No.

Abstract Introduction An iteration of artificial intelligence (AI), large language models (LLMs), such as ChatGPT, have recently gained popularity as a potential educational resource for patients, students, and researchers. LLMs utilize deep learning algorithms to predict the next word in a sequence based on a data library of 300 billion words. Recent studies have shown that while LLMs provide useful information, they are limited due to producing false and nonsensical information. A focus of studies has been on the utility of ChatGPT as an educational resource to patients and learners; however, no study has investigated the utilization of ChatGPT to write a scientific review. AI- generated systematic reviews would be valuable to the dynamic field of urology, especially in terms of research and innovation. Objective Considering the limitations of ChatGPT in performing data analysis, the aim of this project was to assess the utility of AI in constructing introductions of a systematic review on urologic issues and to compare these AI-generated introductions to published introductions written by humans. Methods ChatGPT (4.0), available at www.chat.openai.com, was used to construct three introductions to three different systematic reviews on the following topics: testosterone therapy and cardiovascular events, safety and efficacy of noninvasive therapies for Peyronie’s disease, and erectile dysfunction after radical prostatectomy. Introductions from published systematic reviews in each of the above topics were also obtained. Five different experts in these topics, who were blinded to which introductions were AI generated, reviewed then assessed the introductions for the following parameters: completeness, engagement, accuracy, logic, and clarity of objective. Introductions were assessed for baseline literary differences as well. Results There were no significant differences in the words, characters, number of sentences, and length of sentences between AI-generated introductions compared to those written by humans. There was a statistically significant difference in word length, with AI having a lower average of word length. AI scored significantly higher on average in the categories of completeness and engagement. We did not observe a significant difference between the two groups in the other categories. These observed findings demonstrate that AI can synthesize urologic literature (sexual medicine/men’s health) and generate introductions of a systematic review that are minimally noninferior and possibly superior regarding engagement and completeness. The limitations from this study include a small sample size (5) and the exclusive focus on AI-generated introductions rather than other AI-generated sections of a systematic review. Conclusions Our study reveals that ChatGPT, as an LLM, can provide a noninferior, possibly superior, introduction to a systematic review on topics of urologic sexual medicine and men’s health. As more facets of AI are developed, such as data integration and analysis, AI could be used to generate entire systematic reviews noninferior to those written by humans. Ethical principles of using AI in scientific literature should be examined and discussed prior to the development of more enhanced LLMs. Disclosure No.

Abstract Background The efficacy and safety of collagenase Clostridium histolyticum (CCH) have been demonstrated in the treatment of men with Peyronie’s disease (PD); however, the pivotal clinical trials excluded men with ventral penile curvature. Aim The study sought to evaluate outcomes of CCH treatment in men with ventral curvatures secondary to PD. Methods Men with PD treated with CCH were identified from a prospective database. Patients received up to 4 series of CCH injections using a progressively modified protocol over time. Results were compared between those with baseline ventral vs nonventral penile curvatures. Outcomes Changes in penile curvature, Peyronie’s Disease Questionnaire scores, International Index of Erectile Function scores, nonstandardized assessments, and adverse events. Results A total of 560 men with PD (85 ventral curvature, 475 nonventral curvature) were included in the analysis. Baseline median curvature was 60.0° (interquartile range, 48.8°-75.0°) in the ventral cohort and 65.0° (interquartile range, 45.0°-80.0°) in the nonventral cohort. Median change from baseline penile curvature was −25.0° in the ventral cohort vs −24.0° in the nonventral cohort (P = .08, between-group comparison), which corresponded to curvature reductions of 44.7% and 33.6%, respectively (P = .03). In the subset of patients who completed CCH treatment (ie, received 8 injections or discontinued early because of patient satisfaction with curvature reduction), median change from baseline was −35.0° in the ventral cohort vs −25.0° in the nonventral cohort (P < .05); median percent improvement was 48.3% and 37.5%, respectively (P = .11). Median change from baseline in Peyronie’s Disease Questionnaire and International Index of Erectile Function domain scores and adverse events were similar between cohorts, with the exception of possibly higher hematoma rates in the nonventral group (50% vs 37%; P = .05). No urethral injuries were sustained in either cohort. Clinical Implications Data support the use of CCH for the treatment of ventral as well as nonventral penile curvatures in men with PD. Strengths and Limitations Study strengths are the inclusion of a general clinical population of men with PD, the prospective design, and the relatively large series of men with ventral curvature. Limitations include the single-center and observational nature of the study. Conclusion CCH was safe and effective in the treatment of both ventral and nonventral penile curvatures in men with PD.

Abstract Introduction Age is often correlated with various medical conditions, including bother with the condition itself. Peyronie’s disease (PD) is a condition which is most often associated with men in their 50-60’s, however, it does affect younger men as well. Anecdotally, younger men with PD appear to be more bothered by their condition compared to older men. We therefore sought to evaluate whether there is a difference among older vs younger men as to the degree of bother linked to PD. Objective To evaluate age as a potential predictor of bother associated with PD. Methods A prospective database has been maintained of men seeking treatment for PD. Beginning in Feb 2020, we began implementing men routinely completed standardized intake questionnaires relating to PD, including the Peyronie’s Disease Questionnaire (PDQ). The PDQ consists of 15 questions broken down into three key subdomains: psychological and physical, penile pain, and symptom bother. Men who had completed the PDQ questionnaire were evaluated to determine the correlation between various clinicopathologic variables and the PDQ-bother domain. Results A total of 645 men were seen for symptoms of PD and had PDQ questionnaire data available for review. Baseline demographics included a mean age was 51.8 years (SD 17.6), mean PD symptom duration 31.3 months (SD 65.3), estimated curve of 40.9 degrees (SD 26.8), and mean PDQ-Bother score 8.9 (SD 3.1 – Note: lower is better). Several clinicopathology variables were found to be associated with increased PDQ-bother scores, including age (younger = less bothered, parameter estimate -.0.03, p=0.03), the presence of indentation or hourglass (yes 9.4, no 8.4, p<0.05), pain (yes 9.3, no 8.5, p=0.16), PD preventing penetrative intercourse (yes 9.5, no 8.7, p=0.07), penile shortening (yes 9.3, no 8.7, p=0.10), subjective erectile dysfunction (yes 9.6, no 8.5, p<0.01), and subjective premature ejaculation (yes 9.8, no 8.4, p<0.01). Interestingly, several variables did not correlate, including the duration of relationship, frequency of intercourse, duration of symptoms, direction of curve, degree of curvature, partner pain with intercourse, or libido. Conclusions Several notable factors are associated with PD bother (as assessed by the PDQ-bother domain), and equally importantly, several factors are surprisingly not associated (e.g. curvature degree and direction). These factors provide useful information to the practicing clinician to help better identify men who may be at greater risk for bother associated with the condition. Disclosure No

Abstract Introduction Obstructive azoospermia accounts for up to 14% of patients presenting for fertility evaluation. Fine-needle vasography (FNV) is a diagnostic procedure that can be performed to identify an obstruction proximal to the ejaculatory duct. Compared to traditional vasography, FNV utilizes a less-invasive method to perform imaging of the vas deferens and distal ejaculatory structures. Herein we report our experience performing FNV in a series of patients with suspected complete or near-complete obstruction. Objective To report our experience using FNV to identify a site of obstruction and determine candidacy for reconstructive procedures in patients presenting with suspected obstructive azoospermia or cryptozoospermia. Methods We report a multi-Institutional case series of patients with suspected complete or partial obstructive azoospermia. Patients that were included had azoospermia or severe oligoasthenospermia, presence of palpable vasa, testicles ≥12 ml, and FSH <7.6 IU/L. All patients underwent testicular biopsy prior to or at the time of FNV to confirm spermatogenesis. Fine-needle vasography was performed using a 25F angiocatheter, with radio-opaque dye visualized under fluoroscopy. Descriptive statistics are reported as median and interquartile range (IQR). Results A total of 16 patients underwent vasography between 2014 and 2022 with three surgeons. Twelve patients presented with azoospermia, and four with severe oligoasthenospermia. Median age at vasography was 35.0 (IQR 17) years. Median pre-vasography semen parameters were sperm concentration 0 million/mL (IQR 0.3), sperm motility 0% (IQR 1), semen volume 2.5 mL (IQR 2.5), and semen pH 8.0 (0.7). Median total testosterone was 445 ng/dL (IQR 433), and FSH 4.5 IU/L (IQR 3.6). Half of patients had a history of inguinal hernia repair, unilateral in two and bilateral in six cases. History of genitourinary infection was present in six (35.3%) patients. A total of 7 (44%) men were found to have distal obstruction on FNV, while 8 (50%) were offered epididymovasal reconstruction. Of the seven patients diagnosed with obstruction/atresia of the vas deferens within the inguinal canal and/or pelvis, only two were related to prior inguinal hernia repair. Of the eight men with prior inguinal hernia repairs, two were confirmed to have an obstruction at the level of the inguinal canal. Of the six patients with a history of genitourinary infection, four had an obstruction at the level of the epididymis (with normal FNV), while two had atresia of the vas deferens in the pelvis. Conclusions Fine-needle vasography is an effective, minimally-invasive way to identify the site of complete or partial obstruction in patients presenting with suspected obstructive azoospermia or severe oligoasthenospermia. It additionally permits identification of men who are candidates for epididymovasostomy reconstruction and helps to differentiate between ejaculatory duct obstruction and other causes of blockage. Disclosure No

Abstract Introduction Since the FDA approval of Collagenase Clostridium Histolyticum (CCH), few studies have been able to identify variables which predict curve improvements, with baseline extent of curvature most highly correlated. In addition to extent of baseline curvature, our team has previously identified curve direction and plaque calcification as additional predictive variables. We therefore sought to create an integrated predictive model which incorporated several factors to better estimate anticipated outcomes. Objective To report outcomes of a novel scoring system designed to better predict outcomes of men undergoing CCH injections for Peyronie’s disease (PD). Methods A prospective database has been maintained of men undergoing CCH injections for PD. Data were reviewed to identify variables predictive of curve improvements in men with isolated curvature as well as among those with key characteristics, including indentations, hourglass deformities, penile tapering, and calcification. A predictive model was subsequently developed to improve correlations between disease factors and subsequent CCH outcomes. The final model (CLINiC Score) assigned points as follows: +1 point for every 10 degrees of curvature (C for Curvature), +5 points for penile narrowing >25% (IN for INdent), +3 points for narrowing 0-25%, -4 points for pure lateral curvatures (L for Lateral), and -2 points for plaque calcification (C for Calcification). Patients were assigned scores based on the CLINiC model, and results were correlated with final curve outcomes. Results A total of 476 PD men were included in the current analysis. Baseline variables for the cohort included a mean age of 55.6 yrs (SD 10.9), PD duration 31.9 months (SD 61.4), composite curvature 64.6 degrees (SD 23.9), 47% with indentations, 42% with hourglass deformity, and 17% with calcification. The mean CLINiC score for the cohort was 6.9 (SD 3.4). For the overall cohort, the use of the CLINiC score increased the correlation coefficient from 0.35 to 0.46 (r-squared 0.13 vs 0.21), with a predictive linear formula of 2.1 - 3.2 * CLINiC score. The difference was more pronounced among a subset cohort of men who had pure lateral curvatures, plaque calcification, or narrowing deformity. In comparing the CLINiC predictive model to baseline curve alone, the correlation coefficient increased to 0.54 (r-squared 0.29, p<0.0001) compared to 0.38 (r-squared 0.15, p<0.001). The linear equation to predict curve improvement outcomes using the CLINiC score was 2.2 - 3.5 * total CLINiC score. Conclusions Use of a novel scoring system (CLINiC) improves upon baseline curvature alone to predict post-CCH curve improvements, with the difference more pronounced among men with pure lateral curvatures, plaque calcification, and/or narrowing deformities. External validation is warranted. Disclosure No

Abstract Introduction Limited data currently exist on the role and efficacy of additional series of collagenase clostridium histolyticum (CCH) injections among Peyronie’s disease (PD) men who have previously failed a first series of injections. We have previously reported outcomes of men undergoing a more aggressive protocol for CCH injections. We therefore sought to evaluate results of men who had previously failed CCH injections to determine if they would respond to a repeat course using a more aggressive protocol. Objective To evaluate outcomes of a novel, aggressive protocol for CCH injections among men who had previously failed 6-8 CCH injections using a traditional approach. Methods A randomized, controlled trial (NCT05108558) is ongoing. All participants had previously failed to achieve ≥20% curvature improvement with 6-8 prior CCH injections. Men are randomized 3:1 to receive either CCH + traction (RestoreX) + sildenafil (treatment) up front or initial observation followed by treatment (controls). Outcomes are subsequently compared between treatment and control groups. Key measures include objective curve improvements, and standardized / non-standardized questionnaires, with assessments obtained at baseline, 6-weeks after completion of CCH (treatment arm), after the no treatment period (controls), and at 1 year. Results A total of 11/40 men have been randomized to date, with one having completed four series of CCH injections, three completing one series, and three completing two series. The average age of the cohort is 64.4 years, with a mean PD duration of 28.1 months. Mean baseline curvature was 82.9 degrees (composite curve). The average estimated improvement with prior CCH injections (before enrollment in the current study) was 10%. Preliminary outcomes of men who had completed one series and had a follow-up curve assessment available (n=3) demonstrated an absolute improvement of 28.3 degrees (42%). Of the one patient who completed four full series, the absolute curve improvement was 55 degrees (65%). The overall range of improvement among the four men was 20 to 55 degrees or 31 to 65%, with no patients failing to experience improvements thus far. Conclusions Preliminary data suggests that a repeat course of CCH using a previously described more aggressive administration protocol is effective at improving penile curvature in the majority of men. It is unclear if the improvements are due to the difference in administration protocol, or due to the repeat course of CCH alone. Given the very preliminary nature of the current results, additional data, including external validation, are warranted. Disclosure Yes, this is sponsored by industry/sponsor: Endo Pharmaceutical Clarification Industry funding only - investigator initiated and executed study