ASCO GU 2023: Neoadjuvant Chemotherapy Versus Adjuvant Chemotherapy in Patients with Clinically Node-Positive Upper Tract Urothelial Cancer (UTUC) Who Underwent Radical Nephroureterectomy

( The 2023 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 16th and 18th was host to a prostate cancer and urothelial carcinoma poster session. Dr. Karan Jatwani presented his group’s study evaluating neoadjuvant versus adjuvant chemotherapy in patients with clinically node-positive upper tract urothelial carcinoma (UTUC) who underwent a radical nephroureterectomy (RNU).

UTUC is less common and associated with a worse stage-for-stage prognosis compared to corresponding patients with urothelial carcinoma of the bladder. The POUT trial demonstrated a superior disease-free survival for pT2–T4 pN0–N3 M0 or pTany N1–3 M0.patients receiving adjuvant platinum-based chemotherapy for 4 cycles, when compared to observation.1 However, less than 10% of patients in this trial had lymph node involvement. Conversely, CheckMate 274 revealed a decreased benefit with adjuvant nivolumab in UTUC compared to bladder cancer on post hoc analysis.2 As such, the preferred sequence of perioperative systemic therapy in node positive UTUC remains unclear.

The investigators queried the National Cancer Database to identify adult patients with clinically node positive (cTanyN1-3M0) UTUC diagnosed between 2004 and 2018. Patients were assigned into one of two groups based on the perioperative treatment strategy – neoadjuvant or adjuvant chemotherapy. Patients who did not undergo a RNU were excluded from analyses. Frequency distributions were compared using Fisher’s exact and Mann Whiney U tests. Multivariable Cox Proportional Hazards regression analysis was used to evaluate predictors of overall survival. Multivariable models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index.

A total of 862 patients were identified, of whom 362 (42%) underwent neoadjuvant chemotherapy, and 500 (58%) received adjuvant chemotherapy. No significant differences were noted between the groups regarding age, sex, or insurance status.

Patients with cT1-2 UTUC received neoadjuvant chemotherapy more often (27.9% vs 11.8%, p<0.001), while those with cT3-4 disease more frequently received adjuvant chemotherapy (38.9% vs 57.4%, p<0.001). Rates of neoadjuvant versus adjuvant chemotherapy were not significantly different based on clinical N stage (P = 0.35).

Overall survival in the neoadjuvant group was significantly longer than in the adjuvant group (median of 47.1 vs. 20.2 months, log-rank P < 0.001). On multivariable analysis, only the sequence of perioperative chemotherapy was independently predictive of overall survival hazard (Hazard Ratio of 1.38 for adjuvant chemotherapy, 95% CI: 1.14 to 1.68, p=0.001).

The authors concluded that in this retrospective analysis of outcomes among patients with clinically node positive UTUC who underwent a radical nephroureterectomy, neoadjuvant chemotherapy use, compared to adjuvant chemotherapy, was associated with a significantly improved overall survival hazard.

Presented by: Karan Jatwani, MD, Clinical Fellow, Medical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023. 


  1. Birtle A, et al. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet 2020;395(10232):1268-1277.
  2. Bajorin DF, et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med 2021;384:2102-2114.