Diagnostic uncertainty of clinical T2 disease and its impact on treatment stratification in upper tract urothelial carcinoma: a multicenter retrospective study.

Accurate clinical staging of upper tract urothelial carcinoma (UTUC) remains challenging, and discrepancies between clinical and pathological T stages may result in missed opportunities for appropriate treatment. This study aimed to elucidate real-world discrepancies between clinical and pathological T staging in UTUC, emphasizing the diagnostic uncertainty associated with clinical T2 (cT2) disease. A retrospective analysis was conducted involving 739 patients with cTa–4N0M0 UTUC who underwent radical nephroureterectomy (RNU) at multiple institutions. Patients who received neoadjuvant therapy or had missing pathological T stage data were excluded. Discrepancies between clinical and pathological staging, treatment patterns, and survival outcomes were evaluated. Among 739 patients, substantial discrepancies between clinical and pathological T stages were observed, with an overall diagnostic concordance rate of 44.7%. Only 16% of cT2 cases were pathologically confirmed as pathological T2 (pT2), whereas most were either down-staged to ≤pT1 or up-staged to ≥pT3, indicating marked diagnostic uncertainty. Clinical heterogeneity within the cT2 group resulted in marked survival differences based on pathological stage, as pT3 patients had significantly worse outcomes than pT2 patients. Within the pT3 subgroup, lymphovascular invasion independently correlated with poor prognosis, whereas adjuvant therapy improved survival. However, only approximately one-third of patients with pT3 disease received adjuvant therapy, indicating a treatment gap in this high-risk population. This multicenter study identified real-world discrepancies between clinical and pathological staging in UTUC. cT2 disease represents a heterogeneous and diagnostically uncertain category, requiring careful interpretation for appropriate treatment planning.