Upper tract urothelial carcinoma (UTUC) presents a significant health issue in Taiwan, with incidence rates (3.14–3.41 per 100,000) markedly higher than global averages. Avelumab, an anti-PD-L1 immune checkpoint inhibitor, improves survival as maintenance therapy after first-line chemotherapy in advanced urothelial carcinoma (UC), as shown in the JAVELIN Bladder 100 trial. However, evidence for its use specifically in non-metastatic, node-positive (N+) UTUC is lacking, as this subgroup was not distinctly analyzed. We report two cases addressing this gap.

These cases presented here illustrating a node-positive UTUC diagnosed at our hospital with upfront cisplatin-based chemotherapy after radical nephroureterectomy, followed by avelumab as maintenance therapy.

Case 1 A 54-year-old female (history: chronic hepatitis B, T2DM, hyperlipidemia) presented with left flank soreness/hematuria. Initial investigations in April 2022 comprised a left ureteroscopy biopsy showing high-grade non-invasive papillary UC and the CT scan identified a 2.1 x 6.2 cm enhancing lesion in the left upper/mid ureter causing hydronephrosis, alongside an enlarged (3.6 cm) left common iliac lymph node. The bone scan showed no bone metastases. Laparoscopic left nephroureterectomy in May 2022 confirmed invasive high-grade UC, pT2N2 (external iliac lymph node metastasis >2cm). She received 4 cycles of adjuvant Gemcitabine-Cisplatin (GC) from June-October 2022. Avelumab maintenance therapy started around November 2022. A follow-up CT recently showed continued complete remission. She has tolerated over two years of Avelumab well without immune-related adverse events. Case 2 A 55-year-old female (history: polymyositis, prior thyroid cancer) presented with left flank pain/fever. In March 2024, CT showed a 7.5cm left kidney mass with hilar lymphadenopathy. Laparoscopic left nephroureterectomy in April 2024 confirmed invasive high-grade UC, pT3N2 (metastases in 2/5 hilar nodes), with high PD-L1 (40%). She received 3 cycles of adjuvant GC (May-June 2024). Avelumab maintenance began on September 26, 2024. However, a November 28, 2024 CT revealed a 2.1cm retroperitoneal recurrence. She received salvage radiotherapy (3500 cGy) plus 2 cycles of GC, leading to lesion regression. Avelumab was resumed on March 20, 2025.

These two cases show potential outcomes for avelumab maintenance in high-risk, N+ UTUC post-chemotherapy. Case 1 suggests the potential for durable remission and good tolerability. Case 2 highlights that recurrence can occur despite high PD-L1 expression, but suggests avelumab might still be considered following successful salvage therapy. While limited by the small sample size, these findings provide preliminary real-world insights into avelumab maintenance for N+ UTUC. They demonstrate feasibility and suggest potential clinical activity, underscoring the need for larger studies to confirm efficacy and define the optimal role of this strategy in this specific patient population.