Radiographic paradoxical response in metastatic castrate-resistant prostate cancer (mCRPC) managed with new generation anti-androgens: a retrospective analysis.

BACKGROUND: Prostatic specific antigen (PSA) has well-recognized limitations as a marker for treatment response and disease progression. Post hoc analysis of the PREVAIL trial reported 24.5% of chemotherapy naïve metastatic castration-resistant prostate cancer (mCRPC) patients on enzalutamide had radiographic progression on conventional imaging with nonrising PSA. In this study, we sought to study the discordance of imaging with PSA kinetics in mCRPC patients on second generation anti-androgens (SGA) post-chemotherapy using combined conventional imaging, and new generation imaging in the form of C-11 choline positron emission tomography/computed tomography (C[11] choline PET/CT) scan. METHODS: We retrospectively reviewed the medical records of 123 patients with mCRPC treated with SGA (Abiraterone or Enzalutamide) after docetaxel between 2016 and 2019. Patients underwent PSA testing, and C[11] choline PET/CT scan at baseline level before starting treatment with SGA, then every 3-6 months as part of their follow up evaluation. Loss of response to SGA was defined by increase in corrected maximum standardized uptake value (SUVmax) of pretreatment lesions on C-11 Choline PET/CT, and/or development of new lesions. Suspicious new lesions were confirmed by biopsy and/or conventional imaging. RESULTS: We identified 123 mCRPC patients who received SGA (Abiraterone, n = 106; Enzalutamide, n = 17) after docetaxel. Median duration of therapy was 13.9 months (interquartile range: 8.75-21.14). Approximately 43% (n = 53) of subjects in this study exhibited an increase in choline avidity while on SGA. Of this group, 60.4% of patients experienced a parallel rise in PSA (Group-A), whereas 39.6% displayed a paradoxical response (PR) (Group-B), defined as increased choline avidity combined with stable or down-trending PSA. Median PSA at time of increase in choline avidity was 3.1 ng/ml for Group-A, and 1.3 ng/ml for Group-B (p = 0.0176). Median SUVmax was similar in both groups (4.9 for Group-A, 4.6 for Group-B; p = 0.6072). The median time for increase in choline avidity was 9.5 versus 3.9 months for Group-A versus Group-B, respectively (Log-Rank = 0.0063). CONCLUSION: Nearly 40% of mCRPC patients placed on SGA post docetaxel chemotherapy will exhibit paradoxical responses to therapy, therefore, warranting close follow up with imaging. C-11 choline PET/CT imaging is a useful tool that can help in early predication of disease progression or treatment failure.

Adding carboplatin to chemotherapy regimens for metastatic castrate-resistant prostate cancer in postsecond generation hormone therapy setting: Impact on treatment response and survival outcomes.

BACKGROUND: The clinical course in metastatic castrate-resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after prior treatment with second generation hormone therapy (second HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing second generation hormone therapy. We sought to evaluate three common chemotherapy regimens in this setting. METHODS: We retrospectively identified 150 mCRPC patients with disease progression on enzalutamide or abiraterone. Of these 150 patients, 92 patients were chemo-naïve while 58 patients had previously received docetaxel chemotherapy before being started on second HT. After failing second HT, 90 patients were assigned for docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). A favorable response was defined by more than or equal to 50% reduction in prostate-specific antigen from the baseline level after a complete course of chemotherapy. Survival outcomes were assessed for 30-month overall survival. RESULTS: Patients in group (B) were 2.6 times as likely to have a favorable response compared to patients in group (A) (OR = 2.625, 95%CI: 1.15-5.99) and almost three times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04-8.54) (P = .0442). 30-month overall survival was 70.7%, 38.9% and 30.3% for group (B), (A), and (C), respectively (P = .008). We report a Hazard Ratio of 3.1 (95% CI, 1.31-7.35; P = .0037) between patients in group (A) versus those in group (B) and a Hazard Ratio of 4.18 (95% CI, 1.58-11.06; P = .0037) between patients in group (C) compared to those in group (B) CONCLUSION: This data demonstrates improved response and overall survival in treatment-refractory mCRPC with a chemotherapy regimen of docetaxel plus carboplatin when compared to docetaxel alone or cabazitaxel alone. Further investigations are required.

Initial Experience and Clinical Assessment of the Karl Storz FLEX-XC1 Single-Use Flexible Ureteroscope.

INTRODUCTION: The Karl Storz FLEX-XC1 is a novel single-use flexible ureteroscope that uses the same videographics platform as its reusable digital counterpart. We evaluated the technical performance of the FLEX-XC1 in its initial clinical use. METHODS: We reviewed a series of consecutive ureteroscopy procedures performed by 2 endourologists using the FLEX-XC1 for indications for which we typically use a single-use device: total stone burden > 15 mm or > 10 mm in the lower pole, anticipated case duration > 60 minutes, bilateral procedure, or upper tract urothelial cancer procedures. We assessed device tip deflection, intraoperative mechanical failure, and clinical outcomes for each case. Surgeons rated visual clarity, image quality, and maneuverability on a 1 to 5 Likert scale. RESULTS: Of 29 procedures using FLEX-XC1, 27 (93%) were successfully completed. Preoperative upward deflection was < 270° in 6 (21%) cases, and downward deflection was < 270° in 9 (31%) cases. Three types of intraoperative malfunctions occurred: rotational twisting of deflectable tip (4 cases, 13%), device not advancing through distal ureter (1 case, 3%), and working channel not accommodating a 365-µm laser (1 case, 3%). Visual clarity, image quality, and maneuverability were rated as 5 "very good" or 4 "good" in 100%, 100%, and 97% of cases, respectively. No device-specific or general 30-day complications were observed. CONCLUSIONS: The FLEX-XC1 showed comparable image quality and maneuverability to reusable digital devices. We observed incomplete deflection in up to 31% of cases and mechanical failure in 2 cases. The FLEX-XC1 may be advantageous in prolonged cases where maintaining visual clarity is paramount.

A Survey of Urology Residency Program Directors Assessing Criteria to Interview Applicants during the COVID-19 Pandemic.

INTRODUCTION: We aimed to determine criteria of interest to urology residency program directors when selecting applicants for residency interviews during the COVID-19 pandemic. METHODS: An anonymous survey was sent via email to all urology residency program directors across the United States. Program directors were asked to assign the degree of importance (1-5, with 5 being very important) of selected factors in deciding which applicants to interview. Surveys were distributed and study data were managed using REDCap. Descriptive statistical analyses were performed. RESULTS: In total, 130 urology residency program directors were contacted and 64 (49.3%) responded to the survey. Urology letter(s) of recommendation based on nonvirtual rotation(s), urology clerkship grades, research experience, and visa status of the applicant were cited as the most important factors in selecting applicants for interview with median importance ratings of 5, 4, 4, and 5, respectively. Urology letter(s) of recommendation based on virtual rotation(s), virtual sub-internship(s), and participation in social media activities were the least important in selecting applicants for interviews with median importance ratings of 2 for each. Notably, urology letter(s) of recommendation based on nonvirtual rotation(s) and visa status were consistently ranked as the most important factors by more than 50% of program directors. CONCLUSIONS: Urology program directors value urology letter(s) of recommendation from nonvirtual rotation(s), urology clerkship grades, research experience, and applicant visa status as the most important factors in selecting applicants for interviews during the COVID-19 pandemic. Virtual rotation(s) and social media activity were ranked the lowest among criteria that influence the selection process for interviews.

Comparative Postoperative Outcomes of Rezum Prostate Ablation in Patients with Large Versus Small Glands.

Introduction: Rezum water vapor thermal ablation is a new minimally invasive technique used to treat benign prostatic hyperplasia. Major advantages include minimal anesthesia and recovery time, low rate of sexual side effects, and durable clinical improvement. However, data are lacking regarding use of Rezum in prostate glands >80 cc. Here we seek to examine the clinical outcomes of men with large prostate glands following Rezum. Patients and Methods: We retrospectively reviewed patients who underwent Rezum therapy at our institution since July 2017. Three-month postoperative outcomes were analyzed, including American Urological Association symptom score (AUASS), peak flow, and postvoid residual (PVR). Complications, including hematuria and urinary tract infections, were also assessed. All statistical analyses were conducted using RStudio 1.2.1335. Results: One hundred eighty-two patients undergoing Rezum were identified, of whom 25.8% had prostate volume >80 cc. Mean gland volume in this group was 119 cc and 55.3% were catheter dependent. Following Rezum, statistically significant improvement was seen in AUASS from 22 to 13.4 (p = 0.04) and PVR from 305 to 149 cc (0.05). Statistically significant improvement was seen in peak flow rate from 7.7 to 12.7 mL/second (p = 0.002). In a subset of catheter-dependent patients, the postoperative catheter-free rate was 83% for men with glands >80 cc, which was comparable with 88% in the smaller gland group. Postoperative complication rate was not significantly different between large or small glands. Conclusions: In our experience, Rezum is efficacious in patients with glands >80 cc. Patients experience symptomatic and objective improvement in voiding parameters that is comparable with patients with glands smaller than 80 cc. Among catheter-dependent patients with glands >80 cc, over 80% are catheter free after Rezum. Our experience supports the consideration of Rezum in patients with prostate glands >80 cc; further studies are warranted to confirm long-term outcomes.