Li, Roger

Objectives To compare survival and oncological outcomes of cisplatin‐ineligible patients (Cis‐I) and cisplatin‐eligible (Cis‐E) patients with muscle‐invasive bladder cancer (MIBC) undergoing immediate radical cystectomy (IRC), as IRC is currently considered the standard‐of‐care for Cis‐I patients with MIBC. Patients and Methods Data from patients with clinical (c)T2–4cN0–1M0 MIBC undergoing IRC, between 2006 and 2021, were retrospectively analysed from four tertiary care centres in the United States. Overall, recurrence‐free and event‐free survival were described using the Kaplan–Meier method and tested using the log‐rank test. For context, we compared survival outcomes against those in Cis‐E patients with MIBC undergoing IRC from the Southwest Oncology Group (SWOG)‐8710 trial. Results Overall, 379 Cis‐I and 125 Cis‐E patients with cT2–4cN0–1M0 MIBC who underwent IRC were included. Cis‐I patients included 44.8% cT3/4 vs 60% cT3/4 in the Cis‐E group. Overall, 83.3% of Cis‐I and 79.2% of Cis‐E patients died during follow‐up. The median event‐free and overall survival were 12.1 and 14.5 months for the Cis‐I group and 28.8 and 60.1 months for the Cis‐E group ( P < 0.001). [Correction added on 10 October 2025, after first online publication: The preceding sentence has been revised in this version.] Limitations include retrospective comparison of contemporary multi‐institutional data with that of a randomised control trial. Conclusions The Cis‐I patients with MIBC undergoing IRC fared poorly, with a median overall survival of 14.5 (95% confidence interval 11.1–17.9) months, mostly due to non‐cancer‐related deaths. These results provide a benchmark for clinical trials exploring novel agents or alternative chemotherapy regimens in Cis‐I patients with MIBC.

Objective To further evaluate a genomic classifier (GC) in a cohort of patients undergoing radical cystectomy (RC), as long non‐coding RNA (lncRNA)‐based genomic profiling has suggested utility in identifying a distinct tumour subgroup corresponding to a favourable prognosis in patients with bladder cancer. Patients and Methods Transcriptome‐wide expression profiling using Decipher Bladder was performed on transurethral resection of bladder tumour samples from a cohort of patients with high‐grade, clinically organ‐confined (cTa–T2N0M0) urothelial carcinoma (UC) who subsequently underwent RC without any neoadjuvant therapy ( n = 226). The lncRNA‐based luminal favourable status was determined using a previously developed GC. The primary endpoint was overall survival (OS) after RC. Secondary endpoints included cancer‐specific mortality and upstaging at RC. Results In the study, 134 patients were clinical non‐muscle‐invasive bladder cancer (cTa/Tis/T1) and 92 patients were cT2. We identified 60 patients with luminal favourable subtype, all of which showed robust gene expression patterns associated with less aggressive bladder cancer biology. On multivariate analysis, patients with the luminal favourable subtype (vs without) were significantly associated with lower odds of upstaging to pathological (p)T3+ disease (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.12–0.82; P = 0.02), any upstaging (OR 0.41, 95% CI 0.20–0.83; P = 0.01), and any upstaging and/or pN+ (OR 0.50, 95% CI 0.25–1.00; P = 0.05). Luminal favourable bladder cancer was significantly associated with better OS (hazard ratio 0.33, 95% CI 0.15–0.74; P = 0.007). Conclusions This study validates the performance of the GC for identifying UCs with a luminal favourable subtype, harbouring less aggressive tumour biology.

Objective To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node‐positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. Patients and Methods We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose‐dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1–3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni‐ and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer‐specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. Results Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles ( P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2‐year OS estimates were 63% (95% confidence interval [CI] 0.53–0.74) and 63% (95% CI 0.58–0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni‐ or multivariable Cox regression analyses. Conclusion Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

Objectives To assess the safety profile of antegrade mitomycin gel instillation through a percutaneous nephrostomy tube (PCNT) for upper tract urothelial carcinoma (UTUC) with the aim of decreasing morbidity associated with therapy. Patients and Methods Patients undergoing antegrade administration of mitomycin gel via PCNT were retrospectively included for analysis from four tertiary referral centres between 2020 and 2022. The primary outcome was safety profile, as graded by Common Terminology Criteria for Adverse Events (v5.0). Post‐therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy. Results Thirty‐two patients received at least one dose of mitomycin gel via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen patients (41%) had residual tumour present prior to induction therapy. At a median of 15.0 months following first dose of induction therapy, ureteric stenosis occurred in three patients (9%), all of whom were treated without later recurrence or chronic stenosis. Other adverse events included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%) and haematuria (8%). No patients had impaired renal function during follow‐up and there were no treatment‐related deaths. Seventeen patients (59%) had no evidence of disease at PDE and have not experienced recurrence at a median follow‐up of 13.0 months post induction. Conclusions Administration of mitomycin gel via a PCNT offers a low rate of ureteric stenosis, demonstrates a favourable safety profile, and is administered without general anaesthesia.