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ASCO GU 2025

ASCO GU 2025: Updated Long-Term Follow-up from a Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients with High-Grade Upper Tract Urothelial Carcinoma.

(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA between February 13–15, 2025 was host to a urothelial carcinoma poster session. Dr. Viranda Jayalath presented an updated long-term follow-up from a phase II clinical trial of gemcitabine and cisplatin as neoadjuvant chemotherapy for patients with high-grade upper tract urothelial carcinoma (UTUC).

Level I evidence supports a disease-free survival (DFS) and overall survival (OS) advantage for adjuvant chemotherapy following radical nephroureterectomy (RNU) for men with high-risk upper tract urothelial carcinoma (UTUC), based on the results of the POUT trial.1

However, up to 85% of patients are rendered ineligible for cisplatin-based chemotherapy following radical nephroureterectomy (RNU). Neoadjuvant chemotherapy (NAC) remains an important consideration for high-risk patients. In a multicenter, phase II clinical trial evaluating the role of NAC (gemcitabine-cisplatin) in 57 patients with high-risk localized (N0M0) UTUC, Coleman et al previously reported a pathological response (<ypTN0) rate of 63% and a complete response (CR, ypT0N0/X) rate of 19%. In this presentation, the study investigators reported the final, long-term oncologic outcomes of this trial.

As previously reported, this trial included patients with high-risk UTUC, defined by the presence of high-grade disease and/or radiographically visible invasive-appearing disease (cT2-4a) with positive high urine cytology from the ipsilateral kidney. All patients had evidence of localized disease on axial imaging (i.e., cT2-4a) and had long-term follow-up available. Eligible patients received 4 cycles of split-dose gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once daily on days 1 and 8 of a 21-day cycle. Patients underwent an RNU or distal ureterectomy with templated ipsilateral lymph node dissection within 12 weeks of completing NAC. 

The study outcomes were DFS, CSS, and OS. All outcomes were stratified by pathologic response to NAC, defined as follows:

  • Responders: <ypT2 and N0/X
  • Non-responders: ≥ypT2 or N+

The baseline patient characteristics are summarized below. There were no differences between responders (n=32) and non-responders (n=18). Of the 50 patients available for analysis, 32 (64%) were responders, of which 10 (20%) were CRs. 44/50 patients tolerated ≥3 cycles of neoadjuvant GC
The baseline patient characteristics are summarized below. There were no differences between responders (n=32) and non-responders (n=18). Of the 50 patients available for analysis, 32 (64%) were responders, of which 10 (20%) were CRs. 44/50 patients tolerated ≥3 cycles of neoadjuvant GC
Over a median follow-up of 5.7 years (IQR: 5–7.9 years), 16 progression events, 11 cancer-specific deaths, and 16 total deaths occurred.

For DFS, the 7- and 9-year rates were 63% at both time points. Responders had 7- and 9-year DFS rates of 80% versus 36% among non-responders (p<0.001).

For DFS, the 7- and 9-year rates were 63% at both time points. Responders had 7- and 9-year DFS rates of 80% versus 36% among non-responders (p<0.001). 

For CSS, the 7- and 9-year rates in the overall cohort were 77% and 70%, respectively. Responders had 9-year rates of 79% versus 54% for non-responders (p=0.002).

For CSS, the 7- and 9-year rates in the overall cohort were 77% and 70%, respectively. Responders had 9-year rates of 79% versus 54% for non-responders (p=0.002).
The 7- and 9-year OS rates in the overall cohort were 75% and 54%, respectively. Among responders, the 9-year OS was 67%, compared to 32% among non-responders (p=0.002).The 7- and 9-year OS rates in the overall cohort were 75% and 54%, respectively. Among responders, the 9-year OS was 67%, compared to 32% among non-responders (p=0.002). 

The survival rates by response status for all outcomes are summarized in the table below:

The survival rates by response status for all outcomes are summarized in the table below:
Dr. Jayalath concluded his presentation as follows:

  • Neoadjuvant chemotherapy affords a durable long-term survival advantage for patients with high-risk, non-metastatic UTUC undergoing definitive surgery.
  • Response to NAC is highly predictive of prognosis
  • The role of adjuvant therapy for patients with poor responses to neoadjuvant chemotherapy warrants investigation

Presented by: Viranda Jayalath, MD, SUO Clinical Fellow, Memorial Sloan Kettering Cancer Center, New York, NY

Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025. 

References:
  1. Birtle A, Johnson M, Chester J, et al. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): A phase 3, open-label, randomized controlled trial. Lancet 2020 Apr 18;395(10232):1268-1277.
  2. Coleman JA, Yip W, Wong NC, et al. Multicenter phase II clinical trial of gemcitabine and cisplatin as neoadjuvant chemotherapy for patients with high-grade upper tract urothelial carcinoma. J Clin Oncol. 2023 Mar 10;41(8):1618-1625.