Patient Case 1: Papillary

A 58-year-old woman with newly diagnosed metastatic papillary kidney cancer presents with minimal comorbidities and good performance status. Her symptoms include fatigue, intermittent night sweats, and flank pain, with imaging revealing a large kidney tumor, regional lymphadenopathy, and liver metastases. Laboratory tests show preserved renal function and mild anemia, placing her in an intermediate-risk group based on IMDC criteria. In this setting, treatment decisions are challenging but informed by emerging clinical trial data on non–clear cell renal cell carcinoma (RCC). The primary goal is to select a frontline therapy balancing efficacy and tolerability, while considering molecular profiling to better tailor treatment.

Therapeutic options often include immune checkpoint inhibitor combinations or immunotherapy paired with tyrosine kinase inhibitors. The choice between these depends on symptom burden, potential response rates, and patient preferences. For example, combinations such as lenvatinib plus pembrolizumab or cabozantinib plus nivolumab show promise, with some evidence suggesting higher response rates in symptomatic patients favoring the latter. Comprehensive genomic testing, including next-generation sequencing, is increasingly important to identify actionable mutations such as MET alterations or fumarate hydratase (FH) deficiency, which may guide more personalized treatment strategies or clinical trial enrollment. PD-L1 expression is routinely checked but currently serves more as an informative marker rather than a decisive factor in therapy selection.

For patients with FH deficiency, distinct treatment approaches may be warranted, such as bevacizumab combined with erlotinib, which has shown improved outcomes in this subgroup. Recognizing hereditary syndromes is critical for both prognosis and therapy planning. Clinical trials remain a cornerstone for managing rare non–clear cell RCC, offering access to novel agents and generating data for these understudied populations. Ultimately, treatment decisions should involve detailed discussions about risks, benefits, and patient values, emphasizing multidisciplinary care and personalized medicine.