Bladder cancer is the most common and lethal cancer of the urinary system. Cutaneous metastases from urologic tumors are rare, occurring in around 1% of individuals with advanced cancer.

We present a 70-year-old female with advanced high-grade urinary bladder urothelial carcinoma with glandular differentiation. The patient underwent four courses of neoadjuvant chemotherapy, consisting of Gemcitabine and Cisplatin, followed by robotic-assisted partial cystectomy and bilateral pelvic lymphadenectomy. Postoperatively, she received two courses of adjuvant concomitant chemoradiotherapy with hyperthermia. Despite these interventions, the patient experienced tumor recurrence at the anterior wall and lower bladder neck within 18 months. Further surgical intervention, including radical cystectomy with pelvic lymph node dissection and hysterectomy, was prescribed. Given the progression of the disease, immunotherapy with Pembrolizumab and Enfortumab Vedotin was introduced. The patient later developed erythematous, translucent nodules of various sizes scattered over the pubic area. An excisional biopsy was performed, and the pathological findings confirmed metastatic high-grade urothelial carcinoma. Immunohistochemical (IHC) analysis revealed that the tumor cells were positive for GATA3 and HMWC.

Cutaneous metastasis of urothelial carcinoma is a rare phenomenon, accounting for a small proportion of skin metastases observed in cancer patients with poor prognosis. Nectin-4 expression in rare bladder cancer subtypes, such as pure squamous cell carcinoma or adenocarcinoma variants, and the activity of EV in these individual subgroups, is still unknown. Variant histology was allowed in all EV trials with the caveat that conventional urothelial carcinoma must constitute >50% of the specimens. Some variant histology was present in >77% of patients in the enfortumab and pembrolizumab Cohort A dataset, but outcome by the variant group, or of the individual variant subtypes, was not reported.1 In the conventional urothelial cancer subgroup in previous study, nectin-4 was expressed in 87% of non-muscle-invasive samples (72/83) and 68.2% (15/22) muscle-invasive specimens and 66% of the 6 glandular tumors had mostly strong nectin-4 expression.2 In IHC stain, NECTIN-4 expression decreased in this case and resulted in disease progression.

The prognosis following the onset of cutaneous metastasis is generally poor and Nextin-4 could be a potential biomarker in cutaneous metastasis.