Isolated Urinary Tract Persistence or Progression in Patients Treated With Immunotherapy for Advanced Urothelial Carcinoma

Abstract

Purpose

Emerging therapies including anti-PD-(L)1 immunotherapy have changed paradigms of treatment and improved oncological outcomes of advanced/metastatic urothelial carcinoma (mUC) patients. An emerging challenge in this setting is the management of isolated urinary tract persistence or progression (IUTP) of primary urothelial tumor despite stability or response of metastatic disease to immunotherapy.

Methods

This retrospective monocentric study included all patients treated with single-agent anti-PD-(L)1 for mUC between August 2015 and October 2023. Patients were divided in cohorts of interest depending on primary UC site (lower or upper tract) and previous surgery at the time of immunotherapy initiation. Incidence of IUTP was analyzed in a competitive-risk fashion.

Results

Overall,107 patients with mUC and no previous surgical treatment of primary tumor treated with immunotherapy were at risk of local progression. Among 65 mUC with an untreated bladder primary site, the cumulative incidence rate of IUTP in patients with nonprogressive metastatic disease on immunotherapy was 21.4% and 42.7% at 1 and 2 years, respectively. In responders, half of IUTP were nonmuscle invasive;5 patients, including all 3 with NMIBC, remained free of distant progression after a median follow-up of 12.7 (4.6-41.2) months. In mUTUC, 2 out of 18 patients (11.1%) experienced isolated primary site progression and underwent radical nephroureterectomy, with one patient remaining free of distant progression over 1 year.

Conclusions

These preliminary results show high incidence of IUTP as a progression pattern in mUC patients with clinical benefit of immunotherapy for mUC, highlighting the interest of monitoring the primary tumor and considering local treatment in selected cases, with promising oncological outcomes.