Recent prospective trials and retrospective studies have supported the use of neoadjuvant chemotherapy (NAC) in upper tract urothelial carcinoma (UTUC); however, the optimal number of NAC cycles remains undefined.
We investigated the impact of the number of NAC cycles on pathological response and survival outcomes using a multi-institutional cohort of clinically nonmetastatic high-risk UTUC patients treated surgically.
We performed a retrospective analysis of the UTUC Collaborative Network (UCAN) database, comprising 2,276 patients who underwent radical nephroureterectomy (RNU) across seven high-volume tertiary care centers in the United States (2000-2021). We identified patients who received cisplatin-based NAC before surgery. Primary endpoints included pathologic complete response (pCR: ypT0N0) and noninvasive stage (≤ypT1N0) at surgery. Secondary endpoints included bladder cancer-free survival (BCFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Outcomes were assessed using multivariable logistic regression and Cox proportional hazards models.
Total 187 patients received between 1 and 4 cycles of cisplatin NAC for clinically node-negative (cN0) disease and were eligible for inclusion. 128, 49, and 10 patients received 4, 3, and 1 to 2 cycles of NAC, respectively. No patients who received 1 to 2 cycles achieved pCR, whereas 14% of patients who received 3 to 4 cycles achieved pCR. No significant difference in pCR was observed between 3 and 4 cycles (11% vs. 15%, P = 0.49). On multivariable logistic regression analysis, the number of NAC cycles received was not significantly associated with pCR rates between 3 vs. 4 cycles (OR = 1.38, 95% CI = 0.39-6.51, P = 0.6). In comparing oncologic outcomes on multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with improved OS compared to 3 cycles (HR = 0.34, 95% CI = 0.17-0.69, P = 0.003), but this survival benefit did not extend to MFS, BCFS, or CSS.
pCR rates and cancer-specific oncologic outcomes are similar between patients receiving 3 versus 4 cycles of cisplatin-based NAC prior to RNU for high-risk, clinically nonmetastatic UTUC. Our findings warrant prospective validation to optimize cisplatin-based NAC regimens for high-risk UTUC, balancing efficacy and toxicity.
Urologic oncology. 2026 Feb 28 [Epub ahead of print]
Taibo Li, Stephan Brönimann, Joseph Cheaib, Surena F Matin, Philippe E Spiess, Roger Li, Roderick Clark, Jay Raman, Patrick Hensley, Jonathan Coleman, Vitaly Margulis, Aaron M Potretzke, Jeannie Hoffman-Censits, Nirmish Singla
James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD., James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Urology, Medical University of Vienna, Vienna, Austria., University of Texas MD Anderson Cancer Center, Houston, TX., Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL., Penn State Health Milton S Hershey Medical Center, Hershey, PA., University of Kentucky, Lexington, KY., Memorial Sloan Kettering Cancer Center, New York, NY., UT Southwestern, Dallas, TX., Department of Urology, Mayo Clinic, Rochester, MN., James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD; Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD., James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Urology, Medical University of Vienna, Vienna, Austria; Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41764971