Background/Objectives: Optimal selection for perioperative therapy in urothelial carcinoma (UC) remains uncertain. We evaluated the efficacy of neoadjuvant and/or adjuvant chemotherapy (NAC/AC) for patients with bladder cancer (BC) and upper tract UC (UTUC), examined the role of lymphovascular invasion (LVI), and considered the implications for adjuvant nivolumab. Methods: We retrospectively analyzed consecutive patients who underwent radical cystectomy or radical nephroureterectomy at a single center (July 1998-April 2021; observation to 31 March 2025). After exclusions, 252 BC and 153 UTUC patients were included. Endpoints were cancer-specific survival, progression-free survival (PFS; BC), non-urinary-tract recurrence-free survival (NUTRFS; UTUC), and overall survival (OS). Survival was estimated by Kaplan-Meier analysis and compared by log-rank tests. Results: For BC, AC did not improve the PFS or OS in the overall pT ≥ 2 population, whereas node-positive (pN+) disease derived significant benefits in both endpoints among NAC-naïve patients (PFS and OS, p = 0.002 and p = 0.008). For UTUC, AC conferred no advantage in NUTRFS or OS for the overall pT ≥ 2 population. However, NUTRFS benefits emerged in the pN+ subset (p = 0.049), although the OS was not improved. Among NAC-treated BC, the outcomes were poorest for ≥ypT3 and ypN+, whereas ypT ≤ 2 fared better. LVI was associated with adverse outcomes and was borderline higher in pN+ versus pT ≥ 2/pN- for BC (p = 0.056) and significantly higher for UTUC (p = 0.012). Conclusions: In this retrospective, single-center cohort, our exploratory analyses suggest that perioperative benefit is largely node-dependent, supporting prioritizing systemic therapy for pN+ disease and cautioning against routine AC for pT2/ypT2 without nodal involvement. After NAC, adjuvant therapy appeared most justified for ≥ypT3/ypN+. Prospective biomarker-integrated validation is warranted and, given the small and underpowered subgroups and the potential for selection and immortal time biases, these observations should be interpreted as hypothesis-generating rather than causal.

Bayesian Reanalysis of Adjuvant Nivolumab in Japanese Patients With High-Risk Muscle-Invasive Urothelial Carcinoma.

Efficacy of adjuvant nivolumab in patients with upper tract predominant urothelial carcinoma: A single-center real-world study.

Nivolumab added to cisplatin and radiotherapy versus cisplatin and radiotherapy alone after surgery for people with squamous cell carcinoma of the head and neck at a high risk of relapse (GORTEC 2018-01 NIVOPOST-OP): a randomised, open-label, phase 3 trial.

321P Real-world effectiveness of adjuvant nivolumab in Chinese patients with esophageal cancer/gastroesophageal junction cancer: A retrospective observational study

Sustained high neutrophil-to-lymphocyte ratio during neoadjuvant chemotherapy predicts worse prognosis in patients after esophagectomy for esophageal squamous cell carcinoma.

To evaluate the real-world effectiveness of adjuvant nivolumab following radical surgery in patients with high-risk urothelial carcinoma, using historical data for comparison. Patients who underwent radical surgery at our institution were retrospectively analyzed. They were divided into two groups: one group received adjuvant nivolumab, and the other received no adjuvant therapy. Oncological outcomes, adverse events, and treatment completion rates were assessed. A total of 158 patients were included: 20 in the adjuvant nivolumab group and 138 in the control group. The median observation periods were 20.4 months in the nivolumab group and 36.7 months in the control group. The nivolumab group showed significantly improved recurrence-free survival compared to the control group (hazard ratio: 0.21; 95% confidence interval: 0.10-0.42; p = 0.01). Although overall survival tended to improve in the nivolumab group, the difference was not statistically significant (hazard ratio: 0.32; 95% confidence interval: 0.01-1.01; p = 0.22). Multivariate analysis confirmed adjuvant nivolumab as a significant favorable prognostic factor for recurrence-free survival (hazard ratio: 0.18; 95% confidence interval: 0.044-0.73; p = 0.017). One-year treatment was completed in 55.0% of patients. Adverse events led to discontinuation in 25.0%, with major events including interstitial lung disease (three patients), hormonal disorders such as isolated adrenocorticotropic hormone deficiency (2), rash (3), hypothyroidism (1), and hepatitis (1). Adjuvant nivolumab demonstrated clinical benefit in Asian patients with high-risk urothelial carcinoma in a real-world setting.

Adjuvant programmed cell death protein 1 (PD-1) inhibitors (nivolumab, pembrolizumab) improve recurrence-free survival (RFS) in stage IIB-IIC melanoma, yet no head-to-head trial directly compares them. Traditional indirect methods estimate relative efficacy but often fail to integrate toxicity and patient-level trade-offs. Reinforcement learning (RL) provides a framework to simulate decision-making under uncertainty and competing clinical priorities. We developed an RL model treating each simulated patient as the environment, with state variables including age, ECOG status, stage, time-to-recurrence, and adverse event (AE) outcomes. Actions were treatment choices between nivolumab and pembrolizumab. Rewards combined gains in RFS (+ 1 per 2months) with penalties for grade 3-4 AEs and discontinuations, incorporating both raw and placebo-adjusted AE rates. Q-learning was iterated across 1000 virtual trial episodes until policy convergence. The RL-derived policies reflected conditional treatment preferences rather than a single optimal agent. In scenarios weighted toward tolerability, nivolumab was favored due to lower grade 3-4 AE and discontinuation rates. When incremental RFS gains were prioritized, pembrolizumab emerged as the preferred option. Placebo-adjusted versus raw AE modeling materially influenced the balance of preferences, underscoring the importance of attribution in comparative safety assessment. Our RL framework complements existing comparative methods by making treatment trade-offs explicit and scenario-dependent. Rather than declaring a universal "best" PD-1 inhibitor, the model contextualizes efficacy-toxicity balances, supporting transparent decision-making in settings where small absolute differences may meaningfully influence patient and clinician preferences.

Adjuvant nivolumab versus placebo for high-risk muscle-invasive urothelial carcinoma: 5-year efficacy and ctDNA results from CheckMate 274.

ABSTRACTA 57‐year‐old male with a history of urothelial cancer status post neoadjuvant cisplatin and gemcitabine, cystoprostatectomy and adjuvant nivolumab developed immune checkpoint inhibitor pneumonitis (ICI‐p) following nivolumab treatment. He was treated with steroids but developed recurrent ICI‐p during multiple steroid tapers. Given accumulating side effects from prolonged steroid treatment and the desire to minimise frequent visits to the clinic and infusion center, tocilizumab, which can be administered subcutaneously at home, was considered for steroid‐dependent pneumonitis. Ultimately, he received intravenous followed by subcutaneous tocilizumab, and after a few months of treatment, he was weaned off steroids with sustained resolution of ICI‐p, had improvement in steroid‐related side effects, and had no progression or recurrence of his underlying bladder cancer. To our knowledge, this is the first case of subcutaneous tocilizumab being utilised for steroid‐dependent ICI‐p.

Comparison of adjuvant and neoadjuvant therapies for muscle invasive bladder cancer: A network meta-analysis.

The role of cystectomy in synchronous oligometastatic bladder cancer is unclear. To describe a population-based consecutive cohort with primary oligometastatic bladder cancer (M1a or M1b) treated with curative intent. Methods: Twenty consecutive patients with primary stage M1a or M1b bladder cancer subjected to induction chemotherapy and radical cystectomy 2013-2024 in the Southern healthcare region were identified in the Swedish National Register for Urinary Bladder Cancer. Primary staging and the evaluation of response to systemic induction chemotherapy were performed using [18F]fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET-CT). After additional chemotherapy, consolidating radical cystectomy, lymphadenectomy and in selected patients, postoperative stereotactic radiotherapy or adjuvant nivolumab were applied. Disease-free survival (DFS) and overall survival (OS) from chemotherapy start were visualised by Kaplan-Meier curves. Results: Ten patients with retroperitoneal lymph node metastases, seven with single bone metastasis and three with inguinal metastases responding on three chemotherapy courses according to FDG PET-CT-evaluations were subjected to additional chemotherapy and subsequent radical cystectomy and lymphadenectomy with templates including lymph node metastases. Five patients with bone-oligometastatic disease received consolidating stereotactic radiotherapy, and three patients received adjuvant nivolumab. Postoperatively, one patient progressed in preoperatively known bone metastasis, and one patient displayed lack of chemotherapy response in the cystectomy specimen and was consequently subjected to second-line pembrolizumab treatment with palliative intent. At a median follow-up of 23 months, 10 patients (50%) were disease-free. Long-term survival was observed in some individuals after multimodal treatment for selected patients with synchronous oligometastatic bladder cancer. Amongst patients diagnosed with limited number of distant bladder cancer metastases, those responding on initial systemic chemotherapy can be selected for further treatment. After additional chemotherapy, radical cystectomy with lymphadenectomy and individually intensified treatment with consolidating radiation towards distant metastases and/or adjuvant systemic treatment with checkpoint inhibitors for 12 months, long-term survival was observed in some individuals despite a disease-entity with bad prognostic features.

1612P Characterization of tumor and peripheral biomarkers in patients (pts) with resectable melanoma (MEL) treated with adjuvant nivolumab + relatlimab (NIVO + RELA) or NIVO alone in RELATIVITY-098

1609P Final, 9-year results from the CheckMate 238 phase III trial of adjuvant nivolumab vs ipilimumab in resected stage IIIB–C or IV melanoma

3068O Adjuvant nivolumab vs placebo for high-risk muscle-invasive urothelial carcinoma: 5-year efficacy and ctDNA results from CheckMate 274

1604MO Randomization to adjuvant nivolumab or ipilimumab + nivolumab based on pathological response to a single dose of neoadjuvant nivolumab in stage III melanoma

Background: While immune checkpoint inhibitors have transformed adjuvant therapy for urothelial carcinoma, data focused on upper tract urothelial carcinoma (UTUC) remain scarce. In the CheckMate 274 trial, the UTUC subgroup did not demonstrate a definitive survival benefit. This study aimed to evaluate the clinical outcomes of adjuvant nivolumab in patients with high-risk UTUC.Patients and methods: Of the 41 patients who underwent radical nephroureterectomy for UTUC at our institution between April 2022 and April 2024, 11 received adjuvant nivolumab, thereby retrospectively analyzed. Their treatment adherence and immune-related adverse events (irAEs) and survival outcomes were assessed.Results: Of the 11 patients, eight patients (72.7%) received neoadjuvant chemotherapy. Seven (63.6%) completed the 12-month nivolumab regimen. Four discontinued the treatment because of irAEs (n = 2) and disease recurrence (n = 2). None experienced treatment-related death. The one- and two-year metastasis-free survival rates were 81.8% and 70.1%, respectively, with a median of 30 months. The two-year disease-free and overall survival rates were 40.9% and 79.5%, respectively.Conclusion: This is one of the first real-world experiences focused exclusively on patients receiving adjuvant nivolumab for UTUC. The observed delay in distant progression may reflect the systemic therapeutic activity of immune checkpoint blockade in this setting.

Nivolumab monotherapy has been approved for the adjuvant treatment of adult patients with urothelial carcinoma who are at high risk of recurrence after undergoing radical resection of urothelial carcinoma based on results of the phase 3 CheckMate 274 trial, in which adjuvant nivolumab versus placebo demonstrated improvement in the primary endpoint of disease-free survival (DFS) in high-risk muscle-invasive urothelial carcinoma (MIUC). Identification of biomarkers associated with treatment outcomes can help refine patient selection, and inform on the immunobiology of disease. To assess the relevance of key biomarkers in the adjuvant MIUC setting, extensive exploratory analyses of tumor biomarkers, including associations with DFS, were performed. Differential gene expression and gene signature analysis found that immune-related genes and pathways, in particular a high interferon-γ signature, were predictive of improved DFS in nivolumab-treated patients. Positive predictive and prognostic associations, respectively, were found for CD4 gene expression and measures of CD8 T cell infiltration. A composite predictive model suggested that high tumor cell PD-L1 expression, high CD4 gene expression, high tumor mutational burden score, receipt of neoadjuvant cisplatin and low transforming growth factor-β gene signature score made the greatest contributions to predicting improved outcomes in nivolumab-treated patients. These results reinforce studies establishing the importance of tumor biomarkers of adaptive immunity in influencing response to PD-1-PD-L1 blockade, indicating the potential predictive rather than solely prognostic nature of such findings. ClinicalTrials.gov identifier: NCT02632409 .

An RMST-based analysis of systemic therapy in muscle-invasive bladder cancer.

ABSTRACTIntroductionEnfortumab vedotin plus pembrolizumab (EV + P) shows high efficacy in metastatic urothelial carcinoma (mUC), potentially increasing tumor lysis syndrome (TLS) risk.Case PresentationA 64‐year‐old man with mUC underwent surgery and adjuvant nivolumab after neoadjuvant chemotherapy. Five months post‐surgery, EV + P was initiated for recurrence with distant metastasis. Non‐contrast computed tomography on Day 15 of therapy revealed marked regression of hepatic and pulmonary metastases and significant reduction of the iliac soft tissue mass, with no evidence of infection. The following day, however, laboratory findings were consistent with TLS, followed by hypotension and respiratory failure. He was transferred to the intensive care unit for multidisciplinary supportive management. After stabilization, he was discharged home, and the second cycle of EV + P was completed uneventfully under prophylactic hydration and uric acid–lowering therapy.ConclusionEarly recognition and timely multidisciplinary management are essential for favorable outcomes in TLS following EV + P therapy in mUC patients.