Current Oncology

Neuroendocrine neoplasms (NENs) represent a rare, heterogeneous group of malignancies. Within this tumor entity, primary renal neuroendocrine tumors (PRNETs) are exceedingly rare, with only 160 cases reported worldwide. Due to the absence of native neuroendocrine cells in the renal parenchyma, their cellular origin remains unclear. Clinical and diagnostic challenges are reflected by the low incidence, non-specific clinical presentation, resemblance to common renal neoplasms, and the need for specialized histopathological diagnostic examination. Here, we present the case of a 61-year-old female with an incidentally diagnosed left-sided PRNET in September 2024. This case highlights the diagnostic complexity of PRNET and, importantly, underscores its genomic heterogeneity. It demonstrates a lack of typical renal cell carcinoma (RCC) or common NEN-associated gene alterations, emphasizing their unique molecular landscape.

As societies continue to age, brain tumors increasingly affect older patients. Still, large-scale evidence on whether the relationship between age and brain tumor has been evolving over time is scarce. We examined longitudinal trends among different age groups of patients with brain tumors at 78 German hospitals. Two time periods were compared as follows: phase 1 (1 January 2016–31 December 2019; pre-pandemic) and phase 2 (1 January 2020–31 December 2022; pandemic). Patients were categorized as non-elderly (<65 years) or elderly (≥65 years), and according to 10-year age brackets. The clinical condition was quantified using the Elixhauser Comorbidity Index (ECI) and the Hospital Frailty Risk Score (HFRS). Among the 20,005 patients included, changes in characteristics of non-elderly/elderly patients over time behaved similarly, with improvements in ECI (19.3 to 18.4/15.2 to 14.3; each p < 0.01) and HFRS (2.1 to 1.6/4.7 to 4.1; each p < 0.01), and increases in rates of brain tumor resection (26.1% to 31.8%/22.7% to 27.8%; each p < 0.01). Only patients aged 75–84 years did not follow any of those trends. Over the examined 7-year period, general trends in brain tumor care in elderly subjects resembled those observed in non-elderly patients, except for those aged 75–84 years.

Antibody–drug conjugates (ADCs) have reshaped the treatment landscape of urothelial carcinoma (UC) by enabling selective delivery of highly potent cytotoxic agents to tumor cells. Enfortumab vedotin, sacituzumab govitecan, and HER2-directed ADCs have demonstrated meaningful clinical activity across metastatic and earlier disease settings, with enfortumab vedotin plus pembrolizumab now established as a first-line standard of care. Despite these advances, therapeutic responses remain heterogeneous, and resistance frequently limits durability. This review summarizes current knowledge on predictors of response and mechanisms of resistance to ADCs in UC, highlighting the roles of target antigen expression and heterogeneity, genomic alterations, payload sensitivity, drug efflux transporters, and tumor microenvironmental factors. We discuss emerging biomarkers beyond antigen abundance, patterns of cross-resistance and treatment sequencing, and evolving strategies to overcome resistance, including next-generation ADC design and rational combination therapies. Advancing biomarker-driven patient selection and addressing mechanisms of resistance will be critical to maximizing the durability and clinical impact of ADCs in urothelial carcinoma.