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Intratubular Spread in Renal Pelvic Urothelial Carcinoma: Prognostic Significance and Staging Implications
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DOI：10.1016/j.modpat.2026.101022.png)
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Abstract
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Intratubular spread of renal pelvic urothelial carcinoma refers to tumor extension along pre-existing collecting ducts and/or renal tubules with preservation of the tubular basement membrane at the involved profiles. Although recognized as noninvasive for staging purposes, its prognostic role remains incompletely defined. We conducted a single-center retrospective cohort study of consecutive patients who underwent radical nephroureterectomy for renal pelvic urothelial carcinoma between April 2002 and April 2023, with blinded central slide review and AJCC 8th edition harmonization. The prespecified primary endpoint was non-urinary-tract recurrence-free survival (NUTRFS), defined as recurrence outside the urinary tract (local/regional recurrence outside the urinary tract, lymph node metastasis, or distant metastasis) or death from any cause; urothelial-tract recurrences were not counted as NUTRFS events. The key secondary endpoint was cancer-specific survival (CSS); disease-free survival and overall survival were additional endpoints. After exclusions, 158 patients were analyzed (median follow-up, 95.7 months), and intratubular spread was identified in 58 (36.7%). Within pT1/pT2 disease, the presence of intratubular spread strongly stratified NUTRFS (log-rank P < .001) and CSS (P = .0015), and outcomes for pT1/pT2 tumors with intratubular spread approximated those of pT3 tumors (NUTRFS P = .938; CSS P = .868). Within pT3, the presence of intratubular spread stratified NUTRFS (P = .043) but not CSS (P = .133). In prespecified multivariable Cox models restricted to invasive tumors with known nodal status and excluding pTa/pTis and pT4 (n=71), the presence of intratubular spread remained independently associated with worse NUTRFS (HR 2.85, 95% CI 1.34–6.09; P = .0066) and CSS (HR 2.98, 95% CI 1.28–6.95; P = .0116) after adjustment for pT3 subclass and nodal status, with no evidence of interaction by pT3 subclass. Intratubular spread is a noninvasive but clinically relevant, stage-adjacent histologic feature in renal pelvic urothelial carcinoma that is best captured by NUTRFS and supported by concordant CSS findings, with particular utility for identifying high-risk pT1/pT2 disease.
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