Introduction:

Sarcopenia and skeletal muscle loss are common across metastatic malignancies and are associated with poor prognosis and limited survival. In locally advanced and metastatic urothelial carcinoma (mUC), high prevalence rates have been reported in platinum-treated cohorts, yet their impact on outcomes with the new first-line standard, enfortumab vedotin plus pembrolizumab (EV/P), is unknown. This study evaluates the association of baseline sarcopenia with oncologic outcomes and characterizes changes in body composition during EV/P treatment.

Methods:

We retrospectively identified patients receiving first-line EV/P for mUC at a high-volume tertiary care center between 2024–2025. Patients with available baseline cross-sectional imaging (CT or PET/CT) were included. Skeletal muscle area (SMA) was measured semi-automatically at the L3 vertebral level using Intuition Aquarius software and normalized for height squared to calculate the skeletal muscle index (SMI). Sarcopenia was defined per international consensus criteria as SMI <55 cm²/m² (men) or <39 cm²/m² (women). Baseline demographic and clinical variables were summarized descriptively. Overall survival (OS) and progression-free survival (PFS) were calculated from EV/P initiation to death (OS) or death/progression (PFS), whichever occurred first. Median follow up was calculated with the reverse Kaplan Meier method.

Results:

Among 124 eligible patients treated with EV/P, the median age was 76 years (IQR, 68.8–81), 73.4% were male, and ECOG performance status was 0 in 53.2%, 1 in 19.8%, and ≥2 in 16.9%. Baseline sarcopenia was present in 80.6% of patients. The median interval from baseline imaging to treatment initiation was 28 days (IQR, 13–43.25). Restaging scans were performed a median of 78 days (first) and 190 days (second) after treatment initiation. Median follow-up was 10.8 months. Baseline sarcopenia was not associated with PFS (HR 1.61; 95% CI, 0.67–3.91; p = 0.29) or OS (HR 1.08; 95% CI, 0.47–2.49; p = 0.9). Median SMI and BMI remained stable at both 3 and 6 months, with no significant change from baseline.

Conclusion:

Baseline sarcopenia was common in mUC patients treated with first-line EV/P but did not correlate with survival outcomes. Body composition remained stable over 6 months, suggesting limited early treatment-related muscle loss. Larger studies are warranted to validate these findings and explore the role of sarcopenia in the EV/P era.

Funding: N/A