Abstract
BACKGROUND: Leptomeningeal carcinomatosis is an exceptionally rare pattern of metastases in genitourinary cancer, described in less than 0.1% of cases. We report two cases of patients with metastatic urothelial cancer who initially responded to enfortumab vedotin (EV) before developing leptomeningeal metastases. CASE PRESENTATION: Case 1: A 55 year-old man was diagnosed with metastatic urothelial carcinoma. He was initially treated with cisplatin/gemcitabine chemotherapy, followed by second-line pembrolizumab, with progression on both of these regimens. He was started on EV therapy and had a sustained partial response. After 12 cycles of treatment, he developed neurologic symptoms with imaging showing extensive leptomeningeal metastases. A lumbar puncture was performed with cytology positive for metastatic carcinoma. Case 2: A 63 year-old man was diagnosed with metastatic urothelial carcinoma. He received 6 cycles of platinum/gemcitabine chemotherapy followed by avelumab maintenance, after which he developed radiographic progression. He was started on EV therapy and developed a complete radiographic response. After 13 cycles of treatment, he developed neurologic symptoms and imaging revealed extensive leptomeningeal disease. Cytology confirmed metastatic urothelial carcinoma. CONCLUSION: This uncommon pattern of spread observed in two patients treated with EV in short succession represents a potentially significant and novel pattern of progression within this population.