Durable Response to Immune Checkpoint Inhibition in Small Cell Carcinoma of the Bladder: A Case-Based Review of Immunotherapy and CNS Relapse

Background: Small cell carcinoma of the bladder (SCCB) is a rare, aggressive malignancy with no established standard of care for metastatic disease. The prognosis is dismal; median survival ranges from 12 to 20 months, and long-term survival is exceptional. Case Presentation: We present a 67-year-old man diagnosed in 2018 with metastatic SCCB involving the liver, bone, and ureter. He achieved a complete metabolic response following six cycles of cisplatin–etoposide, followed by consolidative pelvic radiotherapy with a bladder boost. Upon disease progression in 2019, molecular profiling identified a high tumour mutational burden (19.9 mut/Mb), PD-L1 CPS > 1%, and multiple genomic alterations (including MDM2, RAD51D, and TERT). Dual immune checkpoint inhibition (ICI) with ipilimumab and nivolumab was initiated. Although treatment was interrupted and subsequently discontinued due to grade 3 immune-related adverse events, including hepatitis and pneumonitis, the patient maintained a sustained remission off therapy. In January 2025, nearly seven years post-diagnosis, he developed a solitary frontal brain metastasis. He underwent resection and adjuvant stereotactic radiosurgery, achieving local control. He remains under surveillance with no evidence of extracranial recurrence. Conclusions: This case illustrates one of the longest reported survivals in metastatic SCCB. It highlights the utility of molecular profiling in guiding salvage therapy and the potential for durable ICI responses even after discontinuation due to toxicity. Furthermore, late recurrence in the brain emphasizes the central nervous system’s role as a sanctuary site, necessitating prolonged vigilance.