Neoadjuvant Chemotherapy May Offer Greater Chance of Complete Response in Patients With UTUC

Radical nephroureterectomy (RNU) is considered a mainstay treatment for upper tract urothelial carcinoma (UTUC). Neoadjuvant chemotherapy (NAC) has gained popularity due to positive retrospective data demonstrating the treatment’s promising pathological downstaging rates, which act as a proxy end point for improved cancer-specific survival; however, no randomized trials regarding NAC have been published, and series are limited to single centers.

At the 24th Annual Meeting of the Society of Urologic Oncology, Dr. Nicholas Corsi, of UT Southwestern, presented one of the largest multinational studies on NAC in UTUC to date. Developed with colleagues, the study compared the pathological complete response (pCR) and nodal downstaging (NDS) rates of NAC plus RNU versus RNU alone.

Patients involved in the study were part of an international cohort of 13 high-volume cancer centers across the United States, Europe, and Asia, and they received treatment for UTUC between 2011 and 2022. End points included pCR (defined as ≤pT0N0) and NDS (defined as cN > pN).

A total of 72 patients (6.5%) were treated with NAC plus RNU and had a follow-up rate of 26 months, while 1035 patients (93.5%) were treated with RNU alone and had a follow-up of 31 months. The most common NAC regimen was gemcitabine with cisplatin (61%), followed by dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (24%), with a median of 4 cycles.

An inverse probability of treatment weighting-adjusted Cox regression analysis demonstrated that pCR rates were significantly higher in the NAC-plus-RNU arm, with an overall response (OR) of 2.49 (95% CI, 1.75-3.54; P<.001). Patients who received NAC were also significantly more likely to experience NDS, with an OR of 9.56 (95% CI, 4.11-22.26; P<.001).

These real-world data confirm that NAC offers greater odds of achieving pCR for patients with UTUC. However, the results should be viewed through the framework of a retrospective design, and further randomized trials to evaluate the efficacy of NAC are needed.