Background Orthotopic neobladder (ONB) is no longer contraindicated when the distal urethral frozen section (DFS) is negative and only prostatic urethral involvement (PUI) or prostatic stromal invasion (PSI) is present. However, pathology-specific long-term oncologic outcomes remain poorly defined. Methods We retrospectively analyzed 192 margin-negative, pN0M0 men with histologically confirmed PUI or PSI who underwent radical cystectomy between 1996 and 2024. Primary endpoints were urinary tract recurrence (UTR) and distant metastasis. Multivariable Cox regression was performed for distant metastasis. Results Among 192 patients, 54 (28.1%) had PSI and 138 (71.9%) had PUI. ONB was performed in 164 patients (85.4%) and ileal conduit/ureterocutaneostomy (IC/UC) in 28 (14.6%). Over a mean follow-up of 40 months, UTR occurred in 17 patients (8.8%) and was more frequent in PSI than PUI (14.8% vs. 6.5%; HR 3.39, 95% CI 1.31–8.80; p=0.012). Distant metastasis developed in 52 patients (27.1%) and was also more common in PSI (44.4% vs. 20.3%; p<0.001). On multivariable analysis, PSI independently predicted distant metastasis (HR 2.54, 95% CI 1.37–4.72; p=0.003). Metastasis rates did not differ significantly according to diversion type (p=0.165). Conclusions PSI was associated with significantly worse oncologic outcomes than PUI following radical cystectomy. These findings suggest that recurrence and metastatic progression are driven primarily by the extent of prostatic invasion rather than diversion type. ONB after a negative DFS appears oncologically acceptable in carefully selected patients, although PSI warrants closer surveillance.
Objective To evaluate the impact of transurethral resection of the bladder tumour (TURBT) on the release of circulating tumour cells (CTCs) in patients suspected of having muscle-invasive bladder cancer (MIBC) and to assess metastasis in follow-up analysis. Materials and methods In this prospective pilot study for the BladParadigm trial, patients suspected of having MIBC were recruited and underwent TURBT for local staging. Peripheral blood samples were collected just before and immediately after TURBT. CTCs were enriched using the Parsortix® PR1 microfluidics system. Cytokeratin-positive CTCs were counted using fluorescence microscopy. Progression and survival were evaluated at 2 years since inclusion. Results Of 18 patients included, seven were diagnosed with NMIBC and eleven with MIBC. Of all MIBC patients, 1 patient was already CTC-positive before TURBT. Four other MIBC patients were CTC-positive only after TURBT, indicating a CTC rise after TURBT in 40% (4/10) of pre-TURBT CTC-negative MIBC cases. Two out of these four patients experienced progression within two years, of whom one deceased. Two out of six CTC-negative patients before and after TURBT also experienced progression. Conclusion We demonstrate the feasibility of using label-free enrichment to capture and enumerate bladder cancer-derived CTCs. Our findings indicate that TURBT might lead to the spread of CTCs. Although this feasibility study lacks power, the detection of TURBT-associated CTCs suggests a need to study non-invasive alternatives for local staging of bladder cancer.
Introduction We sought to characterize concordance of surveillance and treatment patterns in a large community-based healthcare system with the American Urologic Association/Society of Urologic Oncology (AUA/SUO) guideline for low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). We expect the results of this study to improve the oncologic care of patients with NMIBC. Methods This was a retrospective cohort study of patients aged 18 years or older diagnosed with low- or intermediate-risk NMIBC between 1/1/2018 and 12/31/2022 and followed until 12/31/2024. The prevalence of single-dose post-operative intravesical chemotherapy instillations, cystoscopy procedures, and urine cytology tests were used to determine at, below, and above guideline-concordance. Results A total of 631 low-risk and 619 intermediate-risk NMIBC patients were identified. Prevalences of single-dose immediate postoperative intravesical chemotherapy were: 35.2% (low-risk) and 36.8% (intermediate-risk). In the low-risk NMIBC group, average guideline-concordance was 47.5% for cystoscopy and 82.3% for cytology. In the intermediate-risk group, average guideline-concordance was 54.1% for cystoscopy and 27.2% for cytology. Percent of cystoscopy procedures exceeding guideline-concordance was 30.5% and 14.5% in the low- and intermediate-risk NMIBC groups, respectively. Discussion Although guideline-concordance of single-dose intravesical instillations, cystoscopy procedures, and cytology tests mirrored what is reported in the literature, the prevalence of cystoscopy and cytology tests exceeding guideline-concordance was notably less, which may be a feature of our integrated delivery and finance system. Conclusion Understanding the current landscape of concordance with the AUA/SUO guideline is necessary for every healthcare delivery system to optimize the oncologic care of patients with NMIBC.
Background Guidelines recommend intravesical Bacillus Calmette-Guérin (BCG) as adjuvant therapy for intermediate- and high-risk non-muscle-invasive bladder cancer after transurethral resection. In the event of BCG failure, hyperthermic intravesical chemotherapy (HIVEC) represents a treatment alternative to patients who are surgically inoperable, or decline radical cystectomy. Objective The aim of this study was to evaluate oncological outcomes in patients receiving epirubicin-based HIVEC as a second-line therapeutic approach. Methods Retrospective inclusion of patients from our prospectively maintained, multicenter HIVEC database, who underwent HIVEC due to recurrent or persistent high-grade NMIBC following adequate BCG therapy (BCG failure) between November 2016 and December 2024. Survival was evaluated using Kaplan–Meier analysis and log-rank testing. Associations between clinicopathological factors and oncological outcomes were assessed using Cox regression analysis. Results Sixty-five patients were included. Median follow-up was 38 months (IQR 21–55). Twenty-four patients (36.9%) experienced intravesical recurrence with a median intravesical recurrence-free survival (RFS) of 24 months (IQR 9-45) and 1-/2-year intravesical RFS rates of 77.9% and 64.1%, respectively. Extravesical recurrence was observed in 21 patients (32.3%) with a median extravesical RFS of 22 months (IQR 7-43) and 1-/2-year extravesical RFS rates of 81.3% and 70.9%, respectively. Higher number of recurrences prior to HIVEC were significantly associated with extravesical recurrence in univariate (HR 2.23; 95% CI 1.23-3.87; p=0.019) and multivariate analysis (HR 1.31; 95% CI 1.03-1.67; p=0.027). Conclusions Although limited by the relatively small sample size, Epirubicin-based HIVEC demonstrated promising oncological outcomes indicating its potential value as bladder-preserving treatment option after BCG failure. Prospective controlled studies are warranted to further assess the role of epirubicin-based HIVEC in this setting.
Background Large animal models of bladder cancer are lacking. Objective This study aimed to develop and characterize a transgenic porcine model of bladder cancer (BC) using Oncopigs expressing Cre-inducible KRAS G12D and TP53 R167H mutations. Methods Eleven female Oncopigs underwent tumor induction via three cystoscopic inoculation procedures: Procedure I (N = 3, 1 inoculation/pig), chemical dissolution of the glycosaminoglycan layer with N-Dodecyl-β-d-Maltoside DDM followed by adenoviral Cre-recombinase (AdCre) instillation; Procedure II (N = 4, 3 inoculation/pig), mechanical mucosal denudation followed by AdCre instillation; and Procedure III (N = 4, 3 inoculation/pig), cystoscopy-guided submucosal injection of AdCre. Animals were clinically monitored throughout follow-up (14–28 days). Tumor development was assessed on cystoscopy and ultrasonography, and pathologically, immunohistochemically (IHC), and genomically characterized. Results All pigs remained clinically healthy. Tumors developed at 59% (16/27) of inoculation sites: nine (33%) were neoplastic and seven (26%) were inflammatory. Procedure I achieved 100% neoplastic tumors and produced both non-muscle invasive (71%) and muscle-invasive (29%) tumors. Procedure II achieved 50% neoplastic tumors, all of which were muscle invasive (100%). Procedure III generated only inflammatory tumors. Histologically, neoplastic tumors were pathologically interpreted as urothelial cell carcinomas with sarcomatoid differentiation, with IHC confirming the presence of both epithelioid and sarcomatoid features with abundant mixed leukocytic infiltrates. Genomic analyses verified Cre-induced alterations alongside other mutations seen in human BC. Conclusions We herein demonstrate an efficient and reproducible method for developing autochthonous neoplastic bladder tumors in Oncopigs that resemble human bladder cancer of varying stages. This large animal model facilitates the evaluation of novel surgical and intravesical therapies in BC.
