Immunotherapy-based treatment in renal collecting duct carcinoma: A retrospective case series analysis.

Objective: Collecting duct carcinoma (CDC), a rare and aggressive renal cell carcinoma (RCC) subtype, lacks effective standard therapies for advanced stages. While immune checkpoint inhibitors (ICIs) are standard in clear cell RCC (ccRCC), their role in CDC is poorly defined, supported mainly by case reports. This study evaluated the efficacy and safety of ICI-based therapy in CDC patients.

Materials and methods: This single-center retrospective case series included 11 pathologically confirmed CDC patients treated with ICI-based regimens between January 2015 and December 2024. Primary outcome was objective response rate (ORR; RECIST v1.1). Secondary outcomes included progression-free survival (PFS), overall survival (OS), and grade ≥3 treatment-related adverse events (TRAEs; CTCAE v5.0).

Results: Median age was 59 years; 81.8% were male. Ten patients with metastatic disease and received immunotherapy as systemic treatment, while one received it as adjuvant therapy. Lines of immunotherapy-based treatment included: first-line (9 instances), second-line (4 instances), and third-line or beyond (2 instances). Regimens included: ICI monotherapy (n = 4 instances), ICI + chemotherapy (n = 4), ICI + targeted therapy (n = 8), and ICI + anti-HER2 ADC (RC48) (n = 1). With a median follow-up of 29 months, median OS was 42 months. Systemic ICI therapy yielded an ORR of 43.8% and disease control rate (DCR) of 81.3%. Notably, targeted-immunotherapy combinations demonstrated an ORR of 50%. One patient achieved partial response (PR) with third-line ICI + RC48 (PFS 8 months). Two exceptional cases achieved sustained complete responses (CR) exceeding 56 and 64 months, respectively. Grade ≥3 TRAEs occurred in 36.4% of patients, managed without treatment-related deaths.

Conclusion: This retrospective analysis provides preliminary evidence that ICI-based therapy, particularly targeted-immunotherapy combinations, exhibits promising antitumor activity and manageable safety in CDC patients, with some achieving deep and durable responses. The observed efficacy of targeted-immunotherapy (ORR 50%) and the potential signal with anti-HER2 ADC warrant further investigation.