The 80-W KTP GreenLight laser vaporization of the prostate versus transurethral resection of the prostate (TURP): adjusted analysis of 5-year results of a prospective non-randomized bi-center study.

This study aims to compare long-term results of photoselective vaporization of the prostate (PVP) with an 80-W potassium titanyl phosphate (KTP) laser and monopolar transurethral resection of the prostate (TURP) in terms of efficacy, durability, and safety in an adjusted patient population. This prospective, non-randomized bi-center study included 120 (PVP) and 68 (TURP) patients in each arm. Patients were evaluated at 60 months of follow-up. Data from 30 (PVP) and 31 (TURP) patients were available for analysis. The primary outcome measurement was the International Prostate Symptom Score (IPSS) at 5 years. Secondary outcome measurements included voiding symptoms (quality of life (QoL) score), micturition parameters (maximal flow rate, Q max), post-void residual (PVR) volume, prostate-specific antigen (PSA) value, and reoperation rate. At study inclusion, voiding symptoms and micturition parameters were comparable between both groups. Age, prostate volume, and the proportion of patients with platelet aggregation inhibition or oral anticoagulation were significantly higher in the PVP group. No significant difference could be detected between patients available at 60 months and those lost to follow-up in terms of preoperative characteristics in either group. Sixty months postoperatively, the improvement of IPSS, QoL, Q max, and PVR volume showed no significant difference between both groups. PSA reduction was significantly higher after TURP. The reoperation rate due to urethral stricture (PVP, 13 %; TURP, none), bladder neck contracture (PVP, 3 %; TURP, none), and persisting or recurrent adenoma (PVP, 18 %; TURP, 3 %) was significantly higher after the 80-W PVP. Eighty-watt PVP leads to comparable functional outcomes to TURP. However, during a long-term follow-up, significantly more reoperations are necessary after PVP with the 80-W KTP laser, suggesting inferior tissue ablation capacity of the 80-W KTP laser.

Efficacy and tolerability of bacillus Calmette-Guérin strain Russia for the treatment of non-muscle-invasive bladder cancer: Analysis of a prospective registry.

INTRODUCTION: Little is known about the efficacy and tolerability of intravesical bacillus Calmette-Guérin (BCG) strain Russia for treatment of non-muscle-invasive bladder cancer (NMIBC) in a middle- European population. METHODS: A prospective collection of outcomes of 101 BCG-naive patients with urothelial bladder carcinoma was carried out between January 2013 and October 2023 at the University Hospital Basel, Basel, Switzerland. Patients underwent BCG (ONCO-BCGSIIL, Serum Institute of India, Pune, India) induction and a maximum of three maintenance cycles within one year. Adverse events were classified according to the World Health Organization rating scale. RESULTS: One-, three-, and five-year recurrence-free survival (RFS) was 75.9%, 65.6%, and 61.6%, respectively. Tumor recurrence was seen in 31.7% of patients. One-, three-, and five-year progression-free survival (PFS) was 100%, 93.4%, and 93.4%, respectively. Cystectomy rate was 8.9%, with progression to muscle-invasive disease seen in two patients. Adverse events occurred in 72.3% of patients, with adverse events >class II seen in 8.9%. No BCG-related deaths occurred. Early cessation due to side effects resulting in non-adequate BCG therapy was seen in 3% of patients during induction and in 1% during maintenance therapy. CONCLUSIONS: BCG Russia was well-tolerated and resulted in comparable RFS and PFS to historical results of prospective clinical trials with other BCG strains. The use of BCG Russia for adjuvant treatment of papillary NMIBC and therapy of carcinoma in situ of the urinary bladder could help alleviate the BCG shortage.

The effect of increased maximum power output on perioperative and early postoperative outcome in photoselective vaporization of the prostate.

BACKGROUND AND OBJECTIVE: Preclinical studies suggest an increased vaporization rate and speed of the 532 nm 180-W XPS GreenLight laser (180-W) compared with the 120-W HPS GreenLight laser (120-W) and the 80-W PV GreenLight laser (80-W). To test the clinical relevance of this observation we analyzed intraoperative data and early postoperative results after photoselective vaporization of the prostate (PVP) with the 180-W, 120-W, and 80-W laser. STUDY DESIGN/MATERIALS AND METHODS: A retrospective pair-to-pair comparison was performed including 80 consecutive patients who underwent PVP for the treatment of benign prostate enlargement with the 180-W, 120-W, and 80-W laser. The groups matched concerning age, prostate volume, PSA-value, and preoperative catheterization. Primary study outcome measurement was PSA-value reduction at 3 months; intraoperative data, perioperative complications, and early postoperative functional course were secondary study outcome measurements. RESULTS: Energy application per case (kJ), preoperative prostate volume (kJ/ml) operating time (kJ/minute), and lasing time (kJ/minute) was significantly higher with the 180-W laser. Prevalence of impaired visibility due to bleeding was comparable between the 180-W and the 120-W laser but significantly lower with 80-W. Duration of hospitalization was shorter with the 180-W laser compared to the former laser systems. During the postoperative course of 3 months voiding parameters and micturition symptoms significantly improved in all groups, the incidence of postoperative dysuria was comparable. Postoperative PSA-value reduction was significantly higher after treatment with the 180-W laser. CONCLUSIONS: With the 180-W laser, higher energy application and higher speed of tissue vaporization leads to increased tissue vaporization compared to the former 120-W and 80-W laser systems. Clinical efficacy and perioperative safety are maintained with the higher powered laser.

Prospective Multicenter Validation of the Stockholm3 Test in a Central European Cohort.

BACKGROUND: It has been shown that the Stockholm3 test decreases overdetection of prostate cancer (PCa) while retaining the ability to detect clinically significant PCa (csPCa) in a Swedish population. However, the test includes potentially population-specific testing of single-nucleotide polymorphisms and has yet not been validated outside Scandinavia. OBJECTIVE: To assess the performance of the Stockholm3 test in discriminating csPCa in a Central European cohort undergoing prostate biopsy (PBx). DESIGN, SETTING, AND PARTICIPANTS: This prospective multicenter validation study was conducted from August 2020 to September 2022 at two centers in Switzerland and one center in Germany. The study involved 342 men undiagnosed with PCa who were scheduled for PBx after prostate-specific antigen (PSA) testing and subsequent magnetic resonance imaging (MRI) of the prostate. Before PBx, participants had a blood sample taken for Stockholm3 testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the accuracy of the Stockholm3 test in detecting csPCa (International Society of Urological Pathology grade group [GG] ≥2) according to the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, and the clinical consequences of using the model. RESULTS AND LIMITATIONS: The Stockholm3 test with a cutoff of 11% for csPCa detection had sensitivity of 92.3% (95% confidence interval [CI] 86.9-95.9%), specificity of 32.6% (95% CI 26.0-39.8%), a positive predictive value of 53.2% (95% CI 47.0-59.2%), and a negative predictive value of 83.6% (95% CI 73-91.2%). It showed superior discrimination for csPCa (AUC 0.77, 95% CI 0.72-0.82) in comparison to PSA (AUC 0.66, 95% CI 0.61-0.72; p < 0.001). Using a Stockholm3 cutoff of 11%, PBx could have been omitted for 73 men (21.0%), and 12/154 (8%) csPCa and 2/72 (2.8%) GG >2 cases would have been missed. Limitations include population selection bias. CONCLUSIONS: Our results show favorable clinical outcomes for the blood-based Stockholm3 biomarker test in a Central European patient cohort. PATIENT SUMMARY: The Stockholm3 blood test shows better accuracy in predicting prostate cancer than the more common PSA (prostate-specific antigen) test.

A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC Immunotherapy in Non-muscle-invasive Bladder Cancer Recurrence After Conventional BCG Therapy: SAKK 06/14.

BACKGROUND: VPM1002BC is a genetically modified Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain with potentially improved immunogenicity and attenuation. OBJECTIVE: To report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. DESIGN, SETTING, AND PARTICIPANTS: We designed a phase 1/2 single-arm trial (NCT02371447). Patients with recurrent NMIBC after BCG induction ± BCG maintenance therapy and intermediate to high risk for cancer progression were eligible. INTERVENTION: Patients were scheduled for standard treatment of six weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment was stopped in cases of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was defined as the recurrence-free rate (RFR) in the bladder 60 wk after trial registration. The sample size was calculated based on the assumption that ≥30% of the patients would be without recurrence at 60 wk after registration. RESULTS AND LIMITATIONS: After exclusion of two ineligible patients, 40 patients remained in the full analysis set. All treated tumours were of high grade and 27 patients (67.5%) presented with carcinoma in situ. The recurrence-free rate in the bladder at 60 wk after trial registration was 49.3% (95% confidence interval [CI] 32.1-64.4%) and remained at 47.4% (95% CI 30.4-62.6%] at 2 yr and 43.7% (95% CI 26.9-59.4%) at 3 yr after trial registration. At the same time, progression to muscle-invasive disease had occurred in three patients and metastatic disease in four patients. Treatment-related grade 1, 2, and 3 adverse events (AEs) were observed in 14.3%, 54.8%, and 4.8% of the patients, respectively. No grade ≥4 AEs occurred. Two of the 42 patients did not tolerate five or more instillations during induction. Limitations include the single-arm trial design and the low number of patients for subgroup analysis. CONCLUSIONS: At 1 yr after treatment start, almost half of the patients remained recurrence-free after therapy with VPM100BC. The primary endpoint of the study was met and the therapy is safe and well tolerated. PATIENT SUMMARY: We conducted a trial of VPM100BC, a genetically modified bacillus Calmette-Guérin (BCG) strain for treatment of bladder cancer not invading the bladder muscle. At 1 year after the start of treatment, almost half of the patients with a recurrence after previous conventional BCG were free from non-muscle-invasive bladder cancer (NMIBC). The results are encouraging and VPM1002BC merits further evaluation in randomised studies for patients with NMIBC.

Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy.

Background: VPM1002BC is a modified mycobacterium Bacillus Calmette Guérin (BCG) for the treatment of non-muscle invasive bladder cancer (NMIBC). The genetic modifications are expected to result in better immunogenicity and less side effects. We report on patient safety and immunology of the first intravesical application of VPM1002BC in human. Methods: Six patients with BCG failure received a treatment of 6 weekly instillations with VPM1002BC. Patients were monitored for adverse events (AE), excretion of VPM1002BC and cytokines, respectively. Results: No DLT (dose limiting toxicity) occurred during the DLT-period. No grade ≥3 AEs occurred. Excretion of VPM1002BC in the urine was limited to less than 24 hours. Plasma levels of TNFα significantly increased after treatment and blood-derived CD4+ T cells stimulated with PPD demonstrated significantly increased intracellular GM-CSF and IFN expression. Conclusion: The intravesical application of VPM1002BC is safe and well tolerated by patients and results in a potential Th1 weighted immune response.

Analysis of AR/ARV7 Expression in Isolated Circulating Tumor Cells of Patients with Metastatic Castration-Resistant Prostate Cancer (SAKK 08/14 IMPROVE Trial).

Despite several treatment options and an initial high response rate to androgen deprivation therapy, the majority of prostate cancers will eventually become castration-resistant in the metastatic stage (mCRPC). Androgen receptor splice variant 7 (ARV7) is one of the best-characterized androgen receptor (AR) variants whose expression in circulating tumor cells (CTCs) has been associated with enzalutamide resistance. ARV7 expression analysis before and during enzalutamide treatment could identify patients requiring alternative systemic therapies. However, a robust test for the assessment of the ARV7 status in patient samples is still missing. Here, we implemented an RT-qPCR-based assay for detection of AR full length (ARFL)/ARV7 expression in CTCs for clinical use. Additionally, as a proof-of-principle, we validated a cohort of 95 mCRPC patients initiating first line treatment with enzalutamide or enzalutamide/metformin within a clinical trial. A total of 95 mCRPC patients were analyzed at baseline of whom 27.3% (26/95) had ARFL+ARV7+, 23.1% (22/95) had ARFL+ARV7-, 23.1% (22/95) had ARFL-ARV7-, and 1.1% (1/95) had ARFL-ARV7+ CTCs. In 11.6% (11/95), no CTCs could be isolated. A total of 25/95 patients had another CTC analysis at progressive disease, of whom 48% (12/25) were ARV7+. Of those, 50% (6/12) were ARV7- and 50% (6/12) were ARV7+ at baseline. Our results show that mRNA analysis of isolated CTCs in mCRPC is feasible and allows for longitudinal endocrine agent response monitoring and hence could contribute to treatment optimization in mCRPC.

GreenLight laser vs diode laser vaporization of the prostate: 3-year results of a prospective nonrandomized study.

BACKGROUND AND OBJECTIVE: Laser vaporization of the prostate is one of the alternatives to transurethral resection of the prostate. Short-term studies report a comparable outcome after laser vaporization with the 532 nm 120-W GreenLight high-performance system (HPS) laser and the 980 nm 200 W high-intensity diode (diode) laser. In this study, we analyzed the intermediate-term results of both techniques. MATERIALS AND METHODS: From January 2007 to January 2008, 112 consecutive patients with symptomatic benign prostate enlargement were nonrandomly assigned to treatment with the GreenLight laser or the diode laser. Perioperative parameters, postoperative functional outcome, complications, and the reoperation rate at 3 years were analyzed. RESULTS: Improvement of voiding symptoms (International Prostate Symptom Score, quality-of-life) and micturition parameters (maximum flow rate, postvoid residual volume) showed no significant difference between the HPS group and the diode group. A significantly higher reoperation rate was observed in the diode group in comparison to the HPS group (37.5% vs 8.9%, p=0.0003) due to obstructive necrotic tissue (16.1% vs 0%, p=0.0018), bladder neck stricture (16.1% vs 1.8%, p=0.008), and persisting or recurrent adenoma (5.4% vs 7.1%, p=0.70), respectively. CONCLUSIONS: Both lasers lead to comparable improvement of voiding parameters and micturition symptoms. Treatment with the 200 W diode laser led to a significantly higher reoperation rate, which might be attributed to a higher degree of coagulation necrosis. Thus, a careful clinical application of this diode laser type is warranted.

Ceramic foam plates: a new tool for processing fresh radical prostatectomy specimens.

Procurement of fresh tissue of prostate cancer is critical for biobanking and generation of xenograft models as an important preclinical step towards new therapeutic strategies in advanced prostate cancer. However, handling of fresh radical prostatectomy specimens has been notoriously challenging given the distinctive physical properties of prostate tissue and the difficulty to identify cancer foci on gross examination. Here, we have developed a novel approach using ceramic foam plates for processing freshly cut whole mount sections from radical prostatectomy specimens without compromising further diagnostic assessment. Forty-nine radical prostatectomy specimens were processed and sectioned from the apex to the base in whole mount slices. Putative carcinoma foci were morphologically verified by frozen section analysis. The fresh whole mount slices were then laid between two ceramic foam plates and fixed overnight. To test tissue preservation after this procedure, formalin-fixed and paraffin-embedded whole mount sections were stained with hematoxylin and eosin (H&E) and analyzed by immunohistochemistry, fluorescence, and silver in situ hybridization (FISH and SISH, respectively). There were no morphological artifacts on H&E stained whole mount sections from slices that had been fixed between two plates of ceramic foam, and the histological architecture was fully retained. The quality of immunohistochemistry, FISH, and SISH was excellent. Fixing whole mount tissue slices between ceramic foam plates after frozen section examination is an excellent method for processing fresh radical prostatectomy specimens, allowing for a precise identification and collection of fresh tumor tissue without compromising further diagnostic analysis.

Potential consequences of low biopsy core number in selection of patients with prostate cancer for current active surveillance protocols.

OBJECTIVE: To compare the performance of the Epstein criteria and the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria in the identification of patients eligible for active surveillance (AS) but treated with radical prostatectomy. MATERIALS AND METHODS: We evaluated the baseline characteristics, final pathologic examination, and prostate-specific antigen follow-up (median 43 months, range 1-118) in a series of 492 consecutive patients with prostate cancer managed by radical prostatectomy without AS from 2001 to 2011 at a single institution. Using the postoperative histologic findings, multivariate analysis was used to identify the preoperative predictors of unfavorable AS selection (Gleason score >6 and/or greater than stage pT2c on the final pathologic examination). Biochemical recurrence-free survival was compared between favorably and unfavorably selected patients. RESULTS: Applying the Epstein and PRIAS criteria, 29.2% and 32.2% of the patients had Gleason score >6 or stage pT3 on final pathologic examination, respectively. After a median follow-up of 35.5 and 38 months, 4.2% and 4.3% of patients developed biochemical recurrence in the Epstein and PRIAS criteria groups, respectively. Patients with unfavorable selection had significantly worse biochemical recurrence-free survival than patients with favorable selection (P <.05). Although the median biopsy core number was 8, a biopsy core number <9 was a significant and independent predictor for unfavorable preoperative AS selection in the PRIAS group. CONCLUSION: We found a non-negligible risk of underestimating unfavorable cancer in patients theoretically qualifying for AS in our cohort. The current use of a sufficient number of biopsy cores might improve the selection process for AS.