72歲女性於根治性膀胱切除術後出現變異型尿路上皮癌之雙側上泌尿道異時性復發

– 案例報告

陳米妮¹、黃子豪^1,2,3、黃逸修^1,2,3

¹台北榮民總醫院 泌尿部；²陽明大學醫學院泌尿學科；³書田泌尿學研究中心

Metachronous Bilateral Upper Urinary Tract Recurrence of Urothelial Carcinoma with Variant Histology after Radical Cystectomy in a 72-Year-Old Female:

A Case Report

Minnie Chen¹, Tzu-Hao Huang^1,2,3, Eric Yi-Hsiu Huang^1,2,3

¹Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan

²Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan

³Shu-Tien Urological Institute, National Yang-Ming University, Taipei, Taiwan

Introduction
Urothelial carcinoma (UC) is the predominant malignancy of the urinary tract and may exhibit variant histology, such as neuroendocrine, plasmacytoid, and sarcomatoid differentiation, which are associated with aggressive behavior and poorer outcomes. Management of muscle-invasive and recurrent disease often involves multimodal therapies. We report a rare case of multifocal and metachronous UC involving the bladder and bilateral upper urinary tracts.

Case Presentation
A 72-year-old woman initially presented in 2021/11 with gross hematuria. TURBT revealed muscle-invasive UC (T2). Repeat TURBT on 2022/01/18 confirmed UC with neuroendocrine differentiation, staged pT2. She received cisplatin plus etoposide with concurrent radiotherapy from 2022/03/21 to 2022/05/05 as trimodal therapy. Follow-up TURBT on 2022/08/26 showed no residual UC.

In 2023/10, recurrence with high-grade UC (T1) and carcinoma in situ was identified. Persistent positive urine cytology in 2024/01 led to TURBT on 2024/02/16, revealing invasive high-grade UC (T2) with plasmacytoid feature. She underwent robotic anterior exenteration with radical cystectomy and ileal conduit reconstruction on 2024/04/08. Pathology showed extensive carcinoma in situ.

Nevertheless, in 2025/01, she developed gross hematuria and back soreness. CT on 2025/03/04 revealed a 1.9 cm mass at the left ureteropelvic junction, which rapidly grew to 2.7 cm in 2025/05. Left nephroureterectomy (NU) on 2025/05/29 showed high-grade UC with sarcomatoid differentiation (pT3).

Unexpectedly, she developed right flank pain, nausea, vomiting, and anuria within two weeks after discharge. On 2025/6/13, percutaneous nephrostomy was performed, and pyelography showed filling defects. Nephroscopy on 2025/6/24 revealed tumor, and biopsy confirmed carcinoma in situ. MRI on 2025/6/28 demonstrated lesions in the collecting system. She underwent right NU with conduit resection on 2025/7/11 and started hemodialysis from 2025/7/12. Final pathology showed high-grade invasive UC (pT3).

After surgery, she underwent regular urology outpatient follow-up with MRI surveillance, which showed stable condition on latest visit in 2026.

Discussion
This case illustrates a rare pattern of multifocal, aggressive, and metachronous urothelial carcinoma growth with variant histology features in spite of optimal treatment. Upper tract UC after radical cystectomy is uncommon, with an incidence of 0.75%–6.4%, and contralateral recurrence is rarer (0.6%–6.9%). In the preset case, right-sided UTUC developed almost immediately after left NU and should be determined as bilateral, concurrent recurrence, which is extremely rare with only a few cases reported.

The patient exhibited multiple variant histologies throughout the disease course, including neuroendocrine, plasmacytoid, and sarcomatoid differentiation, all associated with adverse prognosis. Approximately 8% of UC cases contain more than one histologic subtype, and emerging studies suggest distinct genomic alterations with potential therapeutic implications.

In this patient, despite appropriate treatment, including trimodal therapy and radical cystectomy, the disease recurred rapidly. Diagnosis of upper tract disease after ileal conduit reconstruction is challenging due to limited retrograde access. We performed the left NU based on two consecutive images only without pathology and cytology evidence. The right PCN and nephroscopy were performed after clear counseling about the necessity for tissue diagnosis and the risk of tract seeding.

Emerging evidence suggests that ICIs, administered alone or in combination with antibody-drug conjugates, may soon define a new standard of care for UC. We did not offer such treatments before NUs in this patient due to diagnosis uncertainty, as well as the unclear efficacy in variant histologies and perioperative setting. In the present case, accepting the trade-off of inevitable hemodialysis allowed us to prioritize oncologic outcomes, resulting in successful prevention of disease progression.

Conclusion
This case highlights an aggressive disease course with multiple variant histologies and rare bilateral upper tract recurrence after radical cystectomy. It underscores challenges in diagnosis, surveillance, and management, and the need for improved risk stratification and therapeutic strategies.