Objectives: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre‐enfortumab vedotin era, many patients could not receive third‐line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real‐world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third‐line treatment.Methods: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort.Results: At the median follow‐up of 28.5 months, the median overall survival from first‐line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second‐ and third‐line treatment. Notably, 52% had their treatment terminated before the opportunity for third‐line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil‐to‐lymphocyte ratio (≥3), and low body mass index (<21 kg/m²) at the start of first‐line treatment were independent risk factors for not proceeding to third‐line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three.Conclusions: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.

Ueki H, et al. Investig Clin Urol. 2022 Jul;63(4):415-424. https://doi.org/10.4111/icu.20220028

A 79-year-old female was diagnosed with a right renal tumor with a level II tumor thrombus of the vena cava. presurgical therapy was initiated with a combination of avelumab and axitinib for 3 monthes. Then, she underwent nephrectomy and thrombectomy. Histologically, the primary tumor and tumor thrombus had no viable cells, indicating that pathological complete response was achieved with presurgical tyrosine kinase inhibitor/Immuno-oncology combination therapy. An immunohistological xamination showed very strong staining for tumor-infiltrating lymphocytes in the embolized area of the tumor, with CD8 predominating over CD4.