Venous invasion in upper tract urothelial carcinoma: Diagnostic features and oncologic outcomes

To characterize clinical, radiological and histopathological features of upper tract urothelial carcinoma (UTUC) with venous tumor thrombus (VTT) and assess associated oncological outcomes in patients who underwent radical nephroureterectomy (RNU).

We retrospectively identified consecutive patients with UTUC with VTT who underwent radical nephroureterectomy (RNU) at our institution. Cross-sectional imaging was reviewed by a dedicated genitourinary radiologist, and pathology was reviewed by a dedicated genitourinary pathologist. Clinical characteristics, radiographic features, pathologic features, and oncologic outcomes were analyzed.

Eight patients (median age: 74 years, range: 56-91) with UTUC and macroscopic VTT were identified. Imaging consistently revealed collecting system filling defects, irregular mural thickening, and an infiltrative, noncircumscribed growth pattern. Venous involvement was confined to the renal vein in 63% and extended into the inferior vena cava in 37%. Seventy-five percent of patients had pT4 disease, and 63% had pathologic nodal involvement (pN+). Sarcomatoid differentiation was present in 88% of tumors and was disproportionately enriched within the thrombus component, while absent in nodal metastases. One patient experienced a major complication (Clavien-Dindo ≥ III) from surgery. Over a median follow-up of 13.3 months (IQR: 7.7-41.4), 71% of patients developed metastatic disease, and overall mortality was 62.5%. Two patients received adjuvant chemotherapy following surgery. Notably, one achieved a complete response to pembrolizumab, confirmed radiologically and by circulating tumor DNA (ctDNA) clearance.

UTUC with VTT represents a rare but distinctly aggressive phenotype characterized by advanced local stage, frequent nodal involvement, and a striking prevalence of sarcomatoid differentiation. The consistent enrichment of sarcomatoid elements within thrombi suggests a unique biologic behavior potentially driven by epithelial-mesenchymal transition that may underlie vascular invasion and influence treatment response. Recognizing key imaging features may facilitate accurate diagnosis, avoid misclassification as RCC, and prompt timely multimodal treatment.