Utilization of neoadjuvant chemotherapy (NAC) and pathologic outcomes in upper tract urothelial carcinoma (UTUC).

person Vincent Eric Xu George Washington University School of Medicine, Washington, DC info_outline Vincent Eric Xu, Sarah Azari, Matthew Nicholas Klein, Arthur Drouaud, Phat Chang, Ryan Michael Antar, Olivia French Gordon, Armine Smith, Michael Joseph Whalen

Authors person Vincent Eric Xu George Washington University School of Medicine, Washington, DC info_outline Vincent Eric Xu, Sarah Azari, Matthew Nicholas Klein, Arthur Drouaud, Phat Chang, Ryan Michael Antar, Olivia French Gordon, Armine Smith, Michael Joseph Whalen Organizations George Washington University School of Medicine, Washington, DC, Drexel University College of Medicine, Philadelphia, PA, Johns Hopkins University School of Medicine, Washington, DC Abstract Disclosures Research Funding No funding sources reported Background: UTUC is a rare malignancy with a poorer prognosis compared to bladder urothelial carcinoma. Radical nephroureterectomy (RNU) remains the standard treatment for high-risk UTUC. Considering the decline in renal function with RNU and promising pathologic complete response rates from the phase II trial ECOG-ACRIN 8141, NAC has emerged as a favored perioperative treatment regimen for chemo-eligible patients with high-risk UTUC. However, RCTs exploring NAC's efficacy are absent, and large-scale studies examining NAC's role and predictors for its use are scarce. Methods: This study aimed to assess trends in NAC utilization, determinants for receiving NAC, and pathologic outcomes. The National Cancer Database was queried for patients with high-grade cM0 UTUC treated with RNU from 2004-2019. Outcomes included pathologic response (pR) and pathologic complete response (pCR), defined as ≤pT1pN0/X and pT0pN0/X, respectively. Multivariate regressions were adjusted for relevant patient and tumor characteristics. Results: Of 6,436 patients treated with RNU alone and 209 with RNU and NAC, older age, greater home distance from the treatment facility, and higher comorbidity scores decreased the likelihood of receiving NAC. In contrast, higher cT stage (OR 1.72, p=0.028) and cN+ status (OR 7.40, p<0.001) predicted NAC treatment. NAC was more commonly used in academic centers (OR 2.02, p<0.001). Use of NAC peaked in 2016 at 10%, but dropped to ~2% by 2019. There was minimal nodal response to NAC (23.4% cN+ vs 22.0% pN+). NAC was associated with 34.0% pR and 5.3% pCR rates, increasing the likelihood of pCR (OR 57.5, p<0.001). In cT2-4 UTUC, 19.3% and 7.1% of patients had pR and pCR with NAC, and NAC improved odds of pR (OR 1.78, p=0.024). Conclusions: Our study demonstrated variable NAC use for UTUC, illustrating the evolving landscape of perioperative systemic therapies. We report significant response rates even in cT2-4 UTUC. Our observed poor nodal response to NAC emphasizes the crucial role of retroperitoneal lymph node dissection in staging, regardless of NAC status. We note poor NAC utilization in non-academic settings and among patients living farther from care facilities, underscoring the need for improved care quality in the context of regionalization and multi-disciplinary approaches in UTUC management. RNU Alone RNU & NAC p-value Median Age 73 67 <0.001 Facility Type Non-Academic Academic 4147, 64.4% 2289, 35.6% 97, 46.4% 112, 53.6% <0.001 Comorbidity Index 0 1 ≥2 4192, 65.1% 1437, 22.3% 807, 12.5% 165, 78.9% 32, 15.3% 12, 5.7% <0.001 Tumor Size <2 cm ≥2 cm 984, 15.3% 5452, 84.7% 49, 23.4% 160, 76.6% <0.001 cT <cT2 ≥cT2 2592, 40.2% 3844, 39.8% 69, 33.0% 140, 67.0% <0.001 pT <pT2 ≥pT2 2509, 39.0% 3927, 61.0% 74, 35.4% 135, 64.6% <0.001 cN cN0 cN+ 6219, 96.6% 217, 3.4% 160, 76.6% 49, 23.4% <0.001 pN pN0 pN+ pNx 2644, 41.1% 370, 5.7% 3422, 53.2% 117, 56.0% 46, 22.0% 46, 22.0% <0.001