Small cell neuroendocrine carcinoma (SCNC) of the urinary tract is a rare and aggressive malignancy, representing less than 1% of urinary tract tumors and carrying a worse prognosis than urothelial carcinoma (UC). This report presents a case of SCNC of bladder with recurrence and coexistence with UC in the upper urinary tract after initial treatment.

The medical record from a 57-year-old male diagnosed with SCNC of bladder was reviewed, including clinical presentation, imaging, treatment, histopathology, and follow-up course.

Case Presentation The patient presented with six months of gross hematuria and irritative voiding symptoms. A bladder tumor involving the right ureteral orifice was found, and transurethral resection of bladder tumor confirmed high-grade SCNC (cT2N0M0). Four cycles of neoadjuvant cisplatin-etoposide were received however failed with tumor progression. Robotic-assisted radical cystectomy with pelvic lymph node dissection and U-shaped ileal neobladder reconstruction was done. Final pathology showed SCNC with invasion into perivesical tissue, prostate, and seminal vesicles (pT4aN0), with a high Ki-67 index (>80%) and positive neuroendocrine markers (INSM1, synaptophysin). Six months later, recurrence at right ureteropelvic junction was found. Pathology of right radical nephroureterectomy revealed mixed SCNC and invasive UC. Systemic therapy was planned given the high risk of metastasis and lack of standard protocols for recurrent disease. Treatment overview SCNC of the urinary tract is often diagnosed at an advanced stage and related to poor outcomes, thus requiring an aggressive multimodal approach. For localized disease, neoadjuvant cisplatin-etoposide followed by radical surgery is the most supported regimen, adapted from small cell lung cancer guidelines. SCNC coexists with UC suggesting a common origin from multipotent urothelial stem cells. The concept of field cancerization or clonal spread throughout the urothelium may explain distant urothelial recurrence. Though mixed tumors may have slightly better outcomes than pure SCNC, treatment is dictated by SCNC component due to its aggressive nature. In this case, surgery followed by systemic therapy is considered. Agents include topotecan, taxanes, lurbinectedin, and ifosfamide-based combinations, based on small cell lung cancer experience. Immune checkpoint inhibitors (ICIs) are approved for UC and show promise in SCNC particularly in mixed histology. Emerging therapies including DLL3-targeted agents, PARP inhibitors, or other maintenance immunotherapy are enrolled into trials.

Due to aggressive malignancy and poor prognosis of SCNC, early multimodal therapy is essential for disease control. However, recurrence is common and requires further systemic therapy. This case demonstrates the importance of personalized treatment, close surveillance, and consideration of emerging therapies. Multidisciplinary collaboration and international research are key to improving outcomes.