Abstract
BACKGROUND/AIM: Enfortumab vedotin plus pembrolizumab (EVP) is the preferred first-line treatment for locally advanced or metastatic urothelial carcinomas. However, the optimal therapy duration and the role of consolidative surgery in patients achieving a complete response remain unclear. CASE REPORT: A 75-year-old Japanese man presented with intermittent gross hematuria and was diagnosed with a locally advanced lower ureteral carcinoma with regional lymph node metastasis (cT4N2M0). First-line systemic EVP therapy was initiated. After six cycles, radiologic assessment demonstrated a partial response of the primary tumor and complete resolution of the lymph node metastases. Subsequently, the patient underwent robot-assisted radical nephroureterectomy. Histopathological examination revealed no residual viable carcinoma, confirming a pathologic complete response. No lymph node dissection was performed. Given the lack of pathological confirmation of the nodal response, an additional postoperative cycle of EVP was administered. Systemic therapy was discontinued based on shared decision-making considering concerns regarding cumulative peripheral neuropathy. The patient remained recurrence-free without treatment-related adverse events at 6 months of follow-up. CONCLUSION: This case demonstrates that EVP can induce a pathologic complete response in patients with node-positive upper tract urothelial carcinoma, enabling subsequent surgical consolidation and treatment-free surveillance. Although the optimal criteria for treatment discontinuation remain undefined, a treatment-free strategy may be feasible for selected patients who achieve a strong response to EVP. Further studies are warranted to clarify the role of surgery and to establish evidence-based strategies for treatment duration and discontinuation.