Oncolytic adenoviral therapy plus pembrolizumab in BCG-unresponsive non-muscle-invasive bladder cancer: the phase 2 CORE-001 trial.

Cretostimogene grenadenorepvec is a serotype-5 oncolytic adenovirus designed to selectively replicate in cancer cells with retinoblastoma pathway alterations, previously tested as monotherapy in bacillus Calmette-Guérin (BCG)-experienced non-muscle-invasive bladder cancer. In this phase 2 study, we assessed the potential synergistic efficacy between intravesical cretostimogene and systemic pembrolizumab in patients with BCG-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ (CIS). Thirty-five patients were treated with intravesical cretostimogene with systemic pembrolizumab. Induction cretostimogene was administered weekly for 6 weeks followed by three weekly maintenance infusions at months 3, 6, 9, 12 and 18 in patients maintaining complete response (CR). Patients with persistent CIS/high-grade Ta at the 3-month assessment were eligible for re-induction. Pembrolizumab was administered for up to 24 months. The primary endpoint was CR at 12 months as assessed by cystoscopy, urine cytology, cross-sectional imaging and mandatory bladder mapping biopsies. Secondary endpoints included CR at any time, duration of response, progression-free survival and safety. The CR rate in the intention-to-treat population at 12 months was 57.1% (20 out of 35, 95% confidence interval (CI) 40.7-73.5%), meeting the primary endpoint. A total of 29 out of 35 patients (82.9%, 95% CI 70.4-95.3%) derived a CR at 3 months. With a median follow-up of 26.5 months, the median duration of response has not been reached (95% CI 15.7 to not reached). The CR rate at 24 months was 51.4% (18 out of 35) (95% CI 34.9-68.0%). No patient progressed to muscle-invasive bladder cancer in this trial. Adverse events attributed to cretostimogene were low grade, self-limiting and predominantly limited to bladder-related symptoms. A total of 5 out of 35 patients (14.3%) developed grade 3 treatment-related adverse effects. There was no evidence of overlapping or synergistic toxicities. Combination intravesical cretostimogene and systemic pembrolizumab demonstrated enduring efficacy. With a toxicity profile similar to its monotherapy components, this combination may shift the benefit-to-risk ratio for patients with BCG-unresponsive CIS. ClinicalTrials.gov Identifier: NCT04387461 .

Outcomes following Thulium vapoenucleation of large prostates

ABSTRACT Introduction: Thulium laser VapoEnucleation of the prostate (ThuVEP) is an evolving surgical technique for BPH. Most studies have focused on outcomes in small to medium sized prostates and have originated from Europe and Asia. We sought to describe our experience with ThuVEP for very large prostates in a North American cohort. Materials and Methods: From December 2010 to October 2014, 25 men underwent ThuVEP using the CyberTM® (Quantastem, Italy) thulium laser, all with prostate volume >75mL. Data collected included patient demographics, comorbidities, intraoperative parameters, complications, and post-operative outcomes including maximum flow rate (Qmax), post-void residual (PVR), International Prostate Symptom Score (IPSS), and quality of life score (QoL) in one year of follow-up. Statistical analysis was done using Wilcoxon signed-rank test. Results: At baseline, mean age was 70±9 years and prostate size was 163±62g. Most patients (84%) were in retention and 10 (40%) patients were on anticoagulation. Seven (28%) patients went home the day of surgery (mean hospital stay: 1.2±1.2d). There were 2 intraoperative complications (8%), both cystotomies related to morcellation. Nine patients (36%) experienced a complication, all within 30 days. There were no Clavien ≥III complications. Significant improvements were seen in Qmax, PVR, IPSS, and QoL score at each time interval to 12-months following surgery (all p<0.05). Of 21 patients initially in retention, all were voiding at last follow-up. Conclusions: Our findings suggest that ThuVEP is an effective treatment for BPH in patients with large prostates with sustained results for one year.