Background A combination of axitinib and immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in the treatment of advanced renal cell carcinoma (RCC). This study aims to prospectively evaluate the safety, efficacy, and biomarkers of neoadjuvant toripalimab plus axitinib in non-metastatic clear cell RCC. Methods This is a single-institution, single-arm phase II clinical trial. Patients with non-metastatic biopsy-proven clear cell RCC (T2-T3N0-1M0) are enrolled. Patients will receive axitinib 5 mg twice daily combined with toripalimab 240 mg every 3 weeks (three cycles) for up to 12 weeks. Patients then will receive partial (PN) or radical nephrectomy (RN) after neoadjuvant therapy. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease-free survival, safety, and perioperative complication rate. Predictive biomarkers are involved in exploratory analysis. Results A total of 20 patients were enrolled in the study, with 19 of them undergoing surgery. One patient declined surgery. The primary endpoint ORR was 45%. The posterior distribution of πORR had a mean of 0.44 (95% credible intervals: 0.24–0.64), meeting the predefined primary endpoint with an ORR of 32%. Tumor shrinkage was observed in 95% of patients prior to nephrectomy. Furthermore, four patients achieved a pathological complete response. Grade ≥3 adverse events occurred in 25% of patients, including hypertension, hyperglycemia, glutamic pyruvic transaminase/glutamic oxaloacetic transaminase (ALT/AST) increase, and proteinuria. Postoperatively, one grade 4a and eight grade 1–2 complications were noted. In comparison to patients with stable disease, responders exhibited significant differences in immune factors such as Arginase 1(ARG1), Melanoma antigen (MAGEs), Dendritic Cell (DC), TNF Superfamily Member 13 (TNFSF13), Apelin Receptor (APLNR), and C-C Motif Chemokine Ligand 3 Like 1 (CCL3-L1). The limitation of this trial was the small sample size. Conclusion Neoadjuvant toripalimab combined with axitinib shows encouraging activity and acceptable toxicity in locally advanced clear cell RCC and warrants further study. Trial registration number clinicaltrials.gov, NCT04118855.

Background: Disitamab vedotin (DV, RC48-ADC) has shown promising efficacy and manageable safety as monotherapy or combined with immune checkpoint inhibitors (ICIs) in metastatic urothelial carcinoma (mUC) patients progressing after systemic chemotherapy. This study evaluates the efficacy and safety of RC48-ADC plus ICIs in metastatic upper tract urothelial carcinoma (mUTUC) in a real-world setting. Methods: This retrospective, multicenter study included 198 mUTUC patients treated with RC48-ADC plus ICI at 23 clinical centers between June 2021 and December 2023. Data were analyzed from July to September 2024. Primary endpoint: objective response rate (ORR). Secondary endpoints: progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to objective response, and treatment-related adverse events (TRAEs). Result: Among the patients, 122 (61.6%) received combination therapy as first-line treatment, while 76 (38.4%) as second-line or beyond. ORR was 58.6% (95% CI: 51.4–65.5), with a median PFS of 13.0 months; median OS was not reached. Subgroup analyses showed consistent ORR across all subgroups. Adverse events (AEs) occurred in 79.8% of patients, with grade 3–4 AEs in 19.7%. Common AEs included neuropathy (40.4%), fatigue (26.8%), alopecia (25.3%), and rash (21.7%). The main limitations of this study include its retrospective design and the population of the study only include patients from China, leading to potential selection bias. Conclusions: RC48-ADC combined with ICIs demonstrated robust antitumor activity and a favorable safety profile in real-world mUTUC, particularly in selected patient groups. Further studies are needed to explore its potential in this high-risk population.

Although several programmed cell death (PD)-1 inhibitors are approved for the first-line treatment of advanced urothelial carcinoma, their efficacy remains unknown in cisplatin-ineligible patients with upper tract urothelial carcinoma (UTUC) compared with gemcitabine plus carboplatin. Data for patients with UTUC were retrospectively retrieved from the electronic medical records of nine institutions between 2018 and 2021. Patients considered ineligible for cisplatin who received either PD-1 inhibitors (n = 70) or gemcitabine plus carboplatin (n = 53) were included. Efficacy was assessed using Response Evaluation Criteria in Solid Tumors. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The objective response rate (ORR) was comparable between the PD-1 inhibitor and carboplatin–gemcitabine groups (38.6% versus 41.5%). Median PFS was 5.0 months (95% confidence interval [CI]: 2.0–8.0) in the PD-1 inhibitor group, versus 7.0 months (95% CI: 5.8–8.2) in the carboplatin–gemcitabine group (hazard ratio [HR] = 0.741, 95% CI: 0.485–1.132, p = .166). Median OS was 18 months (95% CI: 4.1–31.9) in the PD-1 inhibitor group, compared with 14 months (95% CI: 12.1–15.9) in the carboplatin–gemcitabine group (HR = 0.731, 95% CI: 0.426–1.256, p = .257). The duration of response was significantly longer in the PD-1 inhibitor group than in the carboplatin–gemcitabine group (not reached vs. 9 months, p < .001). Treatment-related adverse events were less frequent in the PD-1 inhibitor group than in the carboplatin–gemcitabine group (57.1% vs. 77.3%). In conclusion, PD-1 inhibitors displayed promising efficacy with less toxicity and longer DOR in the first-line treatment of UTUC in patients ineligible for cisplatin-based chemotherapy.

Introduction: As a research team of urologists and an anesthetist, we sought to investigate the prognostic significance of American Society of Anesthesiologists (ASA) score in patients with upper tract urothelial cancer (UTUC) after radical nephroureterectomy (RNU). ASA physical status (ASA-PS) classification not only was found to be associated with increased comorbidities but also independently factors for predicting morbidity and mortality. Accurate risk assessment was being particularly important for patients being considered for surgery.Methods: Records for 958 patients with UTUC who underwent RNU were reviewed. Clinicopathologic variables, including ASA-PS, were assessed at two institutions. Overall survival (OS), cancer-specific survival (CSS), intravesical recurrence-free survival (IRFS), and metastasis-free survival (MFS) were estimated using the Kaplan–Meier method and Cox regression analyses. We measured the independent predictive value of ASA-PS for mortality by multivariate regression. Association of ASA-PS and clinicopathologic variables was assessed.Results: The group of patients with ASA = 2/3 had a shorter 5-year OS (67.6% and 49.9%), CSS (72.9% and 58.1%), and MFS (75.1% and 58.5%). The median follow-up time was 39 months. Kaplan–Meier curves showed that the group with ASA = 2/3 had significantly poorer OS, CSS, and MFS. Adjusting for multiple potential confounding factors, multivariate analyses suggested that ASA score was an independent predictor of OS, CSS, and MFS (p = 0.004, p = 0.005, p < 0.001).Conclusion: Higher ASA scores were independently associated with lower survival rate. This capability, along with its simplicity, makes it a valuable prognostic metric. It should be seriously referenced in UTUC patients being considered for RNU.