PURPOSE: TAR-200 is a first-in-class intravesical drug-releasing system designed to provide sustained delivery of gemcitabine in the bladder. TAR-200 alone or in combination with cetrelimab (PD-1 inhibitor) could improve outcomes in patients with bacillus Calmette-Guérin (BCG)–unresponsive high-risk non–muscle-invasive bladder cancer (NMIBC) ineligible for or refusing radical cystectomy. METHODS: In this phase IIb parallel cohort study, patients with BCG-unresponsive carcinoma in situ (CIS) with/without papillary disease received TAR-200 monotherapy (Cohort 2 [C2]), TAR-200 plus cetrelimab (C1), or cetrelimab monotherapy (C3). Patients with BCG-unresponsive high-risk papillary disease–only NMIBC received TAR-200 monotherapy (C4). TAR-200 was dosed through month 24 and cetrelimab through month 18. Primary end points were centrally confirmed overall complete response (CR) rate (C1-3) or disease-free survival (DFS) rate (C4) (ClinicalTrials.gov number: NCT04640623 ). RESULTS: At data cutoff (March 31, 2025), 53, 85, 28, and 52 patients were treated in C1-4, respectively. In C2, CR rate and median duration of response were 82.4% (95% CI, 72.6 to 89.8) and 25.8 months (95% CI, 8.3 to not estimable), respectively. In C4, 6-, 9-, and 12-month DFS rates were 85.3% (95% CI, 71.6 to 92.7), 81.1% (95% CI, 66.7 to 89.7), and 70.2% (95% CI, 51.6 to 82.8), respectively. In C1 and C3, CR rates were 67.9% (95% CI, 53.7 to 80.1) and 46.4% (95% CI, 27.5 to 66.1), respectively. Rates of grade ≥3 treatment-related adverse events (AEs) were 12.9%, 13.5%, 37.7%, and 7.1% in C2, C4, C1, and C3, respectively, and of serious treatment-related AEs, 5.9%, 5.8%, 15.1%, and 3.6%. No treatment-related deaths occurred. CONCLUSION: TAR-200 monotherapy was well tolerated, with a high CR rate, durable responses, and prolonged DFS in patients with BCG-unresponsive high-risk NMIBC. TAR-200 monotherapy offered a more favorable risk-benefit profile versus TAR-200 plus cetrelimab or cetrelimab alone in BCG-unresponsive CIS.

Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.

Purpose: WST11 vascular targeted photodynamic therapy (VTP) is a local ablation approach relying upon rapid, free radical-mediated destruction of tumor vasculature. A phase III trial showed that VTP significantly reduced disease progression when compared with active surveillance in patients with low-risk prostate cancer. The aim of this study was to identify a druggable pathway that could be combined with VTP to improve its efficacy and applicability to higher risk prostate cancer tumors. Experimental Design: Transcriptome analysis of VTP-treated tumors (LNCaP-AR xenografts) was used to identify a candidate pathway for combination therapy. The efficacy of the combination therapy was assessed in mice bearing LNCaP-AR or VCaP tumors. Results: Gene set enrichment analysis identifies the enrichment of androgen-responsive gene sets within hours after VTP treatment, suggesting that the androgen receptor (AR) may be a viable target in combination with VTP. We tested this hypothesis in mice bearing LNCaP-AR xenograft tumors by using androgen deprivation therapy (ADT), degarelix, in combination with VTP. Compared with either ADT or VTP alone, a single dose of degarelix in concert with VTP significantly inhibited tumor growth. A sharp decline in serum prostate-specific antigen (PSA) confirmed AR inhibition in this group. Tumors treated by VTP and degarelix displayed intense terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling staining 7 days after treatment, supporting an increased apoptotic frequency underlying the effect on tumor inhibition. Conclusions: Improvement of local tumor control following androgen deprivation combined with VTP provides the rationale and preliminary protocol parameters for clinical trials in patients presented with locally advanced prostate cancer. Clin Cancer Res; 24(10); 2408–16. ©2018 AACR.

A 61-year-old male presented with gross hematuria and transurethral resection of bladder tumor revealed inflammatory myofibroblastic tumor (IMT). Due to extent of disease leading to ureteral obstruction and hydronephrosis, radical cystectomy (RC) with ileal conduit urinary diversion was performed. Five months after RC, the patient presented with decreased urine output. Exploratory laparotomy revealed mass in right colon and right hemicolectomy revealed metastatic IMT to the bowel and pericolonic fat. To our knowledge, this is the first report of primary IMT of the bladder metastasizing to other organs.

Ureteroscopy is a commonly performed procedure, with post operative pain that can lead to re-visits and opioid prescribing. Perioperative gabapentinoids have shown promise in decreasing pain and opioid use. We hypothesized that single dose perioperative pregabalin would be safe and efficacious for decreasing pain after ureteroscopy. This was an IRB approved and registered blinded, placebo-controlled trial conducted at a single institution. Patients undergoing ureteroscopy without histories that would limit use of opioids, gabapentinoids, and non-steroidal medications were enrolled. Either 300mg pregabalin or placebo was administered 1 hour before ureteroscopy. Pain was assessed using a visual analogue before administration and 1 hour after surgery. Clinical factors, pain scores, a proxy for cognition, patient satisfaction, and opioid prescribing were assessed in the first 30 post operative days. 118 patients were enrolled over a 2-year period. Patients who received pregabalin were younger than those who received placebo (median of 44 years vs 57). Post operative pain scores were higher in those who received pregabalin (3.7 vs 2.0, P = .004), a finding that remained statistically significant when accounting for patient age and preoperative pain scores. There was no difference in the measure of cognition or in reports of adverse events. In this trial evaluating the efficacy of a single dose perioperative pregabalin in ureteroscopy, pregabalin did not decrease postoperative pain when compared to placebo. Urologists should not routinely use this adjunctive medication in ureteroscopy, as it is unlikely to provide benefit.