Durable disease control after multimodal therapy and platinum-based chemotherapy rechallenge in advanced clear cell adenocarcinoma of the urethra with lymph node metastases: a case report

Background: Clear cell adenocarcinoma of the urethra (CCAU) is an extremely rare subtype of primary urethral carcinoma. Owing to its low incidence, the optimal treatment strategy for advanced or metastatic disease remains unclear. We report a case of advanced CCAU with lymph node metastases that achieved long-term disease control following multimodal therapy. Case presentation: A 60-year-old woman presented with urinary retention and was diagnosed with primary urethral clear cell adenocarcinoma (cT4N2M0) with pelvic lymph node metastases. Neoadjuvant gemcitabine plus cisplatin (GC) chemotherapy achieved a partial response and was followed by robot-assisted radical cystourethrectomy combined with hysterectomy, vaginectomy, and pelvic lymph node dissection. Pathological examination revealed ypT4N2M0 disease with negative surgical margins. Adjuvant nivolumab was initiated but was discontinued because of immune-related hypothyroidism and nodal recurrence. Comprehensive genomic profiling demonstrated microsatellite stability, a low tumor mutational burden (1 mutation/Mb), and MET and MYC amplifications. As no actionable alterations were identified, GC chemotherapy was reintroduced and again achieved a partial response. The patient remains progression-free 32 months after diagnosis. Conclusions: This case suggests that multimodal treatment combining radical surgery and platinum-based chemotherapy may contribute to durable disease control in selected patients with advanced CCAU and lymph node metastasis. Although genomic profiling did not directly guide therapy in this case, molecular characterization may provide a basis for future individualized treatment strategies for this rare malignancy.