HER2-low metastatic urothelial carcinoma with liver metastases responding to antibody–drug conjugate therapy: a case report

Abstract Background While HER2-targeted antibody-drug conjugates (ADCs) have shown efficacy in advanced bladder cancer with liver metastases (LM), current guidelines focus on HER2-high (IHC 3+/2+) disease. This case reports a sustained remission in HER2-low (IHC 1+) metastatic urothelial carcinoma (UC) with hepatic dissemination using combination therapy. Case presentation A 73-year-old male presented with painless gross hematuria for three days. Imaging and biopsy confirmed high-grade invasive urothelial carcinoma of the bladder with carcinoma in situ and glandular differentiation. He underwent laparoscopic radical cystectomy with lymph node dissection and ileal conduit diversion. Postoperative pathology showed high-grade invasive urothelial carcinoma, negative lymph nodes, PD-L1 high expression (ICP > 1%, TC 90%) and HER2 (1+). Five months later, surveillance imaging revealed multifocal liver metastases. First-line cisplatin chemotherapy was declined, so he received disitamab vedotin (120 mg every 2 weeks) plus toripalimab (240 mg every 3 weeks). After two cycles, partial response (30% reduction) was achieved, and by 8 cycles near-complete resolution of liver lesions was observed (75% reduction, RECIST 1.1). Transient grade 1 neuropathy was managed by extending the ADC interval to 4 weeks. Treatment was paused after 12 cycles. At 1-year follow-up, the patient maintains sustained remission. Conclusion This hypothesis-generating case suggests that concurrent anti-PD-1 and HER2-targeted ADC may induce deep remission in HER2-low mUC with liver metastases. However, the relative contribution of each agent remains unclear, and high PD-L1 expression alone could explain part of the response. Prospective validation is needed.