IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Patients with Bacillus Calmette­Guérin (BCG)­unresponsive non­muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell­activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically with BCG to elicit durable complete responses (CRs) in this patient population. METHODS: In this open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical NAI plus BCG (cohort A) or NAI alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received NAI plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival were secondary end points for cohort A. RESULTS: In cohort A, CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months (95% CI=9.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan­Meier estimated probability of avoiding cystectomy and of DSS was 89.2% and 100%, respectively. In cohort B (n=72), the Kaplan­Meier estimated DFS rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]). Most treatment-emergent adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%); three grade 3 immune-related treatment-emergent adverse events occurred. CONCLUSIONS: In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer­specific survival at 24 months. The study is ongoing, with an estimated target enrollment of 200 participants (Funded by ImmunityBio.)

Final 5-Year Outcomes of the Multicenter Randomized Sham-Controlled Trial of a Water Vapor Thermal Therapy for Treatment of Moderate to Severe Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: We present final 5-year outcomes of the multicenter randomized sham-controlled trial of a water vapor therapy (Rezum™) for treatment of moderate to severe lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 subjects >50 years of age with International Prostate Symptom Score ≥13, maximum flow rate ≤15 ml/second and prostate volume 30 to 80 cc were randomized and followed for 5 years. From the control arm of 61 subjects, a subset of 53 subjects requalified and after 3 months received treatment as part of the crossover group and were also followed for 5 years. The total number of vapor treatments to each lobe of the prostate was determined by length of prostatic urethra and included middle lobe treatment per physician discretion. RESULTS: Significant improvement of lower urinary tract symptoms was observed at <3 months post-thermal therapy, remaining durable through 5 years in the treatment group (International Prostate Symptom Score reduced 48%, quality of life increased 45%, maximum flow rate improved 44%, Benign Prostatic Hyperplasia Impact Index decreased 48%). Surgical re-treatment rate was 4.4% with no reports of device or procedure related sexual dysfunction or sustained de novo erectile dysfunction. Results within the crossover group were similar through 5 years. CONCLUSIONS: Minimally invasive treatment with water vapor thermal therapy provides significant and durable symptom relief as well as flow rate improvements through 5 years, with low surgical re-treatment rates and without impacting sexual function. It is a versatile therapy, providing successful treatment to obstructive lateral and middle lobes.

Five year results of the prospective randomized controlled prostatic urethral L.I.F.T. study.

INTRODUCTION: To report the five year results of a prospective, multi-center, randomized, blinded sham control trial of the Prostatic Urethral Lift (PUL) in men with bothersome lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: At 19 centers in North America and Australia, 206 subjects ≥ 50 years old with International Prostate Symptom Score (IPSS ) > 12, peak flow rate (Qmax) ≤ 12 mL/s, and prostate volume 30 cc-80 cc were randomized 2:1 to the PUL procedure or blinded sham control. In PUL permanent UroLift implants are placed to hold open the lateral lobes of the prostate to reduce urinary obstruction. After randomized comparison at 3 months and the only opportunity to add more PUL implants, PUL patients were followed to 5 years. LUTS severity (IPSS), quality of life (QOL), BPH Impact Index (BPHII), Qmax, sexual function, and adverse events were assessed throughout follow up. RESULTS: IPSS improvement after PUL was 88% greater than that of sham at 3 months. LUTS and QOL were significantly improved by 2 weeks with return to preoperative physical activity within 8.6 days. Improvement in IPSS, QOL, BPHII, and Qmax were durable through 5 years with improvements of 36%, 50%, 52%, and 44% respectively. No difference was seen between Intent to Treat and Per Protocol populations. Surgical retreatment was 13.6% over 5 years. Adverse events were mild to moderate and transient. Sexual function was stable over 5 years with no de novo, sustained erectile or ejaculatory dysfunction. CONCLUSIONS: PUL offers rapid improvement in symptoms, QOL and flow rate that is durable to 5 years. These improvements were achieved with minimal use of a postoperative urinary catheter, rapid return to normal, and preservation of both erectile and ejaculatory function. Symptom improvement was commensurate with patient satisfaction. PUL offers a minimally invasive option in the treatment of LUTS due to BPH.

Convective Thermal Therapy: Durable 2-Year Results of Randomized Controlled and Prospective Crossover Studies for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia.

PURPOSE: We report 2-year outcomes of a multicenter randomized controlled trial plus 1-year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 men at least 50 years old with I-PSS (International Prostate Symptom Score) 13 or greater, maximum flow rate 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 to thermal therapy with the Rezum® System or a control group. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months control subjects could requalify for crossover study. Convectively delivered radiofrequency thermal energy was delivered into obstructive prostate tissue, including the median lobe as needed. The primary efficacy end point was a change in severity of symptom scores. RESULTS: Convective radiofrequency thermal therapy improved urinary symptoms significantly over controls at 3 months and provided a sustained 51% reduction from baseline at 24 months (p <0.0001). This produced a 5 and 8-point or greater score decrease in 84% and 74% of subjects, respectively, at 24 months. Crossover subject symptoms, flow rate and quality of life measures were markedly improved after thermal therapy compared to after the control procedure (p = 0.024 to <0.0001). No de novo erectile dysfunction was reported. CONCLUSIONS: Convective radiofrequency water vapor thermal therapy is a minimally invasive office or outpatient procedure that provides early effective symptom relief that remains durable for 2 years and is applicable to the median lobe.

24-month durability after crossover to the prostatic urethral lift from randomised, blinded sham.

OBJECTIVE: To evaluate the 24-month effectiveness of the prostatic urethral lift (PUL) procedure in men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) assessed through a crossover study. PATIENTS AND METHODS: In all, 53 patients underwent a sham procedure as part of the blinded, randomised L.I.F.T. (Luminal Improvement Following prostatic Tissue approximation for the treatment of LUTS secondary to BPH) study at 19 centres and elected to enrol in this crossover study. The crossover procedure involved placement of permanent implants (UroLift® system) into the prostatic lateral lobes. Patients were followed for 3 months after the sham procedure and then for 24 months after crossover to PUL, with assessments of urinary symptom relief, quality of life (QoL), urinary flow rate, sexual function, and adverse events. RESULTS: At 24 months after crossover to PUL, the International Prostate Symptom Score (IPSS), QoL, BPH Impact Index, and maximum urinary flow rate improved 36%, 40%, 54%, and 77% from baseline, respectively. Each IPSS parameter on average improved significantly from baseline (P < 0.005) and remained stable throughout follow-up. Symptom response after the sham procedure indicated initial improvement at 1 month with significant decay by 3 months. Adverse events were typically mild to moderate and patients returned rapidly to normal activity. Four patients (8%) required intervention with transurethral resection of the prostate and one patient required additional PUL implants within the 24-month period. There were no reported instances of de novo sustained erectile or ejaculatory dysfunction. CONCLUSIONS: The PUL procedure is associated with rapid symptom relief, increased urinary flow rate and QoL improvement that remain stable over 24 months. Morbidity is low and sexual function is preserved.

Erectile and Ejaculatory Function Preserved With Convective Water Vapor Energy Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: Randomized Controlled Study.

INTRODUCTION: Most surgical treatments for male lower urinary tract symptoms and benign prostatic hyperplasia affect erectile and ejaculatory functions negatively, leading to patient dissatisfaction. AIM: To determine whether water vapor thermal therapy, when conducted in a randomized controlled trial, would significantly improve lower urinary tract symptoms secondary to benign prostatic hyperplasia and urinary flow rate while preserving erectile and ejaculatory functions. METHODS: Men at least 50 years old with International Prostate Symptom Scores of at least 13, a peak flow rate of at least 5 to no higher than 15 mL/s, and prostate volume of 30 to 80 cm(3) were randomized 2:1 between Rezum System thermal therapy and control. Thermal water vapor (103°C) was injected into lateral and median lobes as required for treatment of benign prostatic hyperplasia. The control procedure entailed rigid cystoscopy with simulated active treatment sounds. MAIN OUTCOME MEASURES: Blinded group (active = 136, control = 61) comparison occurred at 3 months and the active arm was followed to 12 months for International Prostate Symptom Score, peak flow rate, and sexual function using the International Index of Erectile Function and the Male Sexual Health Questionnaire for Ejaculatory Function. The minimal clinically important difference in erectile function perceived by subjects as beneficial was determined for each erectile function severity category. Subjects not sexually active were censored from sexual function analysis. RESULTS: No treatment- or device-related de novo erectile dysfunction occurred after thermal therapy. International Index of Erectile Function and Male Sexual Health Questionnaire for Ejaculatory Function scores were not different from the control group at 3 months or from baseline at 1 year. Ejaculatory bother score improved 31% over baseline (P = .0011). Also, 32% of subjects achieved minimal clinically important differences in erectile function scores at 3 months, and 27% at 1 year, including those with moderate to severe erectile dysfunction. International Prostate Symptom Score and peak flow rate were significantly superior to controls at 3 months and throughout 1 year (P < .0001). CONCLUSION: Convective water vapor thermal therapy provides sustainable improvements for 12 months to lower urinary tract symptoms and urinary flow while preserving erectile and ejaculatory functions.

Minimally Invasive Prostate Convective Water Vapor Energy Ablation: A Multicenter, Randomized, Controlled Study for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

PURPOSE: This report reveals the results of a multicenter, randomized, controlled study using transurethral prostate convective water vapor thermal energy to treat lower urinary tract symptoms associated with benign prostatic hyperplasia. MATERIALS AND METHODS: Men 50 years old or older with an International Prostate Symptom Score of 13 or greater, maximum flow rate of 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 between thermal therapy with the Rezum® System and control. Thermal water vapor was injected into the transition zone and median lobe as needed. The control procedure was rigid cystoscopy with simulated active treatment sounds. The primary end point compared International Prostate Symptom Score reduction at 3 months. Treatment subjects were followed for 12 months. RESULTS: There were 197 men randomized (active 136, control 61). Thermal therapy and control International Prostate Symptom Score was reduced by 11.2 ± 7.6 and 4.3 ± 6.9 respectively (p <0.0001). Treatment subject baseline International Prostate Symptom Score of 22 decreased at 2 weeks (18.6, p=0.0006) and by 50% or greater at 3, 6 and 12 months, p <0.0001. The peak flow rate increased by 6.2 ml per second at 3 months and was sustained throughout 12 months (p <0.0001). No de novo erectile dysfunction was reported. Adverse events were mild to moderate and resolved quickly. CONCLUSIONS: Convective water vapor thermal therapy provides rapid and durable improvements in benign prostatic hyperplasia symptoms and preserves erectile and ejaculatory function. Treatment can be delivered in an office or hospital setting using oral pain medication and is applicable to all prostate zones including the median lobe.

Three year results of the prostatic urethral L.I.F.T. study.

INTRODUCTION: To report the three year results of a multi-center, randomized, patient and outcome assessor blinded trial of the Prostatic Urethral Lift (PUL) in men with bothersome lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: At 19 centers in North America and Australia, 206 subjects = 50 years old with International Prostate Symptom Score (IPSS) ≥ 13, peak flow rate (Qmax) ≤ 12 mL/s, and prostate volume between 30 cc-80 cc were randomized 2:1 to the PUL procedure or sham control. PUL involved placing permanent UroLift implants into the lateral lobes of the prostate to enlarge the urethral lumen. After randomized comparison at 3 months, PUL patients were followed to 3 years. LUTS severity (IPSS), quality of life, Qmax, sexual function, and adverse events were assessed throughout follow up. RESULTS: The therapeutic effect of PUL regarding IPSS was 88% greater than sham at 3 months. Average improvements from baseline through 3 years were significant for total IPSS (41.1%), quality of life (48.8%), Qmax (53.1%), and individual IPSS symptoms. Symptomatic improvement was independent of prostate size. There were no de novo, sustained ejaculatory or erectile dysfunction events and all sexual function assessments showed average stability or improvement after PUL. Fifteen of the 140 patients originally randomized to PUL required surgical reintervention for treatment failure within the first 3 years. CONCLUSIONS: PUL offers rapid improvement in voiding and storage symptoms, quality of life and flow rate that is durable to 3 years. Patients demonstrated a level of symptom relief that is associated with significant patient satisfaction. PUL, a minimally invasive procedure, is very effective in treating bothersome LUTS secondary to benign prostatic obstruction (BPO) and is unique in its ability to preserve total sexual function while offering a rapid return to normal physical activities.

Durability of the Prostatic Urethral Lift: 2-Year Results of the L.I.F.T. Study.

INTRODUCTION: For a therapy to become an important part of a provider armamentarium it must be safer or better than existing therapies and be durable. The prostatic urethral lift offers rapid improvement in lower urinary tract symptoms associated with benign prostatic hyperplasia with minimal side effects. We report 2-year results of a multicenter, randomized, blinded trial of the prostatic urethral lift. METHODS: A total of 206 men 50 years old or older with an AUA-SI of 13 or greater, a peak flow rate of 12 ml per second or less and a 30 to 80 cc prostate were randomized 2:1 between the prostatic urethral lift and sham treatment. The prostatic urethral lift is performed by placing permanent transprostatic implants to lift apart the prostate lobes and reduce urethral obstruction. Sham treatment entailed rigid cystoscopy, a blinding screen and sounds that mimicked those of the prostatic urethral lift procedure. Patients were assessed for lower urinary tract symptoms, peak flow rate, quality of life and sexual function. RESULTS: The prostatic urethral lift reduced the AUA-SI 88% more than sham treatment (-11.1 vs -5.9, p = 0.003). Patients with the prostatic urethral lift experienced an AUA-SI reduction from 22.1 at baseline to 18.0 (-17%), 11.1 (-50%), 11.4 (-48%) and 12.5 (-42%) at 2 weeks, 3 months, and 1 and 2 years, respectively (p <0.0001). The peak flow rate was increased 4.2 ml per second at 3 months and 2 years (p <0.0001). By 2 years only 7.5% of patients required additional intervention for lower urinary tract symptoms. Adverse events were typically mild and transient. Encrustation did not develop on implants properly placed in the prostate. There was no occurrence of de novo sustained ejaculatory or erectile dysfunction. CONCLUSIONS: The prostatic urethral lift preserves sexual function and provides rapid improvement in symptoms, flow and quality of life that are sustained to 2 years.

Treatment of LUTS secondary to BPH while preserving sexual function: randomized controlled study of prostatic urethral lift.

INTRODUCTION: We analyzed data obtained from a randomized controlled blinded study of the prostatic urethral lift (PUL) to evaluate the sexual side effects of this novel treatment. AIMS: We sought to determine whether PUL, when conducted in a randomized study, significantly improved lower urinary tract symptoms (LUTS) and urinary flow rate while preserving sexual function. METHODS: Men ≥50 years with prostates 30-80 cc, International Prostate Symptom Score (IPSS) >12, and peak urinary flow rate (Qmax) ≤12 ml/s were randomized 2:1 between PUL and sham. Sexual activity was not an inclusion criterion. In PUL, permanent transprostatic implants are placed to retract encroaching lateral lobes and open the prostatic fossa. Sham entailed rigid cystoscopy with sounds to mimic PUL and a blinding screen. MAIN OUTCOME MEASURES: Blinded groups were compared at 3 months and active arm then followed to 12 months for LUTS with IPSS and for sexual function with sexual health inventory for men (SHIM) and Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD). Subjects were censored from primary sexual function analysis if they had baseline SHIM < 5 at enrollment. Secondary stratified analysis by erectile dysfunction (ED) severity was conducted. RESULTS: There was no evidence of degradation in erectile or ejaculatory function after PUL. SHIM and MSHQ-EjD scores were not different from control at 3 months but were modestly improved and statistically different from baseline at 1 year. Ejaculatory bother score was most improved with a 40% improvement over baseline. Twelve-month SHIM was significantly improved from baseline for men entering the study with severe ED, P = 0.016. IPSS and Qmax were significantly superior to both control at 3 months and baseline at 1 year. There was no instance of de novo sustained anejaculation or ED over the course of the study. CONCLUSIONS: The PUL improves LUTS and urinary flow while preserving erectile and ejaculatory function.

The prostatic urethral lift for the treatment of lower urinary tract symptoms associated with prostate enlargement due to benign prostatic hyperplasia: the L.I.F.T. Study.

PURPOSE: We report the first multicenter randomized blinded trial of the prostatic urethral lift for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. MATERIALS AND METHODS: Men at least 50 years old with AUASI (American Urological Association Symptom Index) 13 or greater, a maximum flow rate 12 ml per second or less and a prostate 30 to 80 cc were randomized 2:1 between prostatic urethral lift and sham. In the prostatic urethral lift group small permanent implants are placed within the prostate to retract encroaching lobes and open the prostatic urethra. Sham entailed rigid cystoscopy with sounds mimicking the prostatic urethral lift. The primary end point was comparison of AUASI reduction at 3 months. The prostatic urethral lift arm subjects were followed to 1 year and assessed for lower urinary tract symptoms, peak urinary flow rate, quality of life and sexual function. RESULTS: A total of 206 men were randomized (prostatic urethral lift 140 vs sham 66). The prostatic urethral lift and sham AUASI was reduced by 11.1±7.67 and 5.9±7.66, respectively (p=0.003), thus meeting the primary end point. Prostatic urethral lift subjects experienced AUASI reduction from 22.1 baseline to 18.0, 11.0 and 11.1 at 2 weeks, 3 months and 12 months, respectively, p<0.001. Peak urinary flow rate increased 4.4 ml per second at 3 months and was sustained at 4.0 ml per second at 12 months, p<0.001. Adverse events were typically mild and transient. There was no occurrence of de novo ejaculatory or erectile dysfunction. CONCLUSIONS: The prostatic urethral lift, reliably performed with the patient under local anesthesia, provides rapid and sustained improvement in symptoms and flow, while preserving sexual function.