Clinical Insights on Evolving Treatment Landscape in Urothelial Carcinoma


Scott T. Tagawa, MD, MS, FACP, FASCO, offers a comprehensive look at the evolving treatment landscape, with a focus on practical considerations and ongoing research.

Case 2: A 76-Year Old Man with Locally Advanced, Resectable Urothelial Carcinoma

Initial Clinical Presentation: 

  • A 76-year-old man presented to the clinic with complaints of dizziness and hematuria.
  • PMH: hypercholesterolemia (well controlled with medication) and mild COPD.
  • SH: Patient does not smoke or drink alcohol.

Initial Clinical Workup: 

  • CT Imaging: Chest, abdomen, and pelvis revealed a 3.5-cm mass in the bladder and multiple liver metastases.
  • ECOG PS 1
  • eGFR > 60 mL/min (cisplatin-eligible kidney function)
  • Lung Biopsy confirmed stage IV urothelial carcinoma.
  • Molecular testing: FGFR2/3 mutation and fusion negative

Treatment and Disease Progression:

  • Patient is initiated with neoadjuvant gemcitabine plus cisplatin for 4 cycles.
    • He achieved a partial response following chemotherapy.
    • Following neoadjuvant therapy, the patient undergoes surgical resection of the tumor.
    • While discussed with his oncology care team, the patient did not receive maintenance treatment.
  • 6 months following surgery, patient demonstrates disease progression based after routine follow up and repeat imaging.
    • Patient progresses to muscle-invasive metastatic urothelial carcinoma.
    • Patient is started on combination pembrolizumab plus enfortumab vedotin-ejfv.
      • Pembrolizumab 200 mg IV every 3 weeks; enfortumab 1.25 mg/kg IV infusion over 30 minutes on Days 1 and 8 for every 21-day cycle.
      • 12 hours post-infusion, the patient developed a maculopapular rash and was improved with supportive care (topical hydrocortisone cream).
    • Achieves partial response after 6 cycles.
  • Following initial systemic therapy, patient is evaluated in a routine follow up visit and demonstrates further disease progression.
    • After discussion with his oncology care team, the patient is initiated on sacituzumab govitecan 10 mg/kg IV on D1 and D8 for 21-day cycles.
      • 48 hours following start of therapy, patient notices feeling dehydrated and having more frequent bowel movements. His oncologist starts him on oral loperamide to manage his diarrhea. Two days later, the patient’s diarrhea was resolved.

This is a synopsis of a Case-Based Peer Perspectives series featuring Scott T. Tagawa, MD, MS, FACP, FASCO, of Weill Cornell Medicine.

Scott T. Tagawa, MD, MS, FACP, FASCO discussed the impact of ongoing platinum shortages on treatment decisions in advanced urothelial carcinoma. He noted that for cisplatin-ineligible patients, the combination of enfortumab vedotin plus pembrolizumab may be utilized based on press release data showing superiority over chemotherapy. However, some cisplatin-eligible patients can still be cured, particularly those with lymph node-only metastatic disease. Therefore, efforts to obtain cisplatin when appropriate should be made.

Beyond emerging immunotherapy combinations, Dr. Tagawa reviewed data presented at recent conferences on targeted therapies. The FGFR inhibitor erdafitinib improved outcomes versus chemotherapy in patients with FGFR activating alterations who progressed after platinum chemotherapy and immune checkpoint inhibition. Ongoing trials are investigating erdafitinib in earlier treatment settings.

He also highlighted additional data from separate cohorts of the TROPHY-U-01 study evaluating the antibody-drug conjugate sacituzumab govitecan. In cisplatin-ineligible patients, response rates were consistent with prior results. Combination with pembrolizumab showed higher response rates but durability remains under investigation.

In conclusion, Dr. Tagawa emphasized the rapid expansion of effective treatment options for metastatic urothelial carcinoma. These provide alternatives when preferred cisplatin-based chemotherapy cannot be accessed. With multiple targeted therapies and immunotherapies now approved, clinical trial enrollment should focus on sequences or combinations aiming to further improve patient outcomes. Molecular profiling to match patients with biomarker-driven precision therapies also remains a priority.

*Video synopsis is AI-generated and reviewed by Urology Times editorial staff.

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