Overview of Urothelial Carcinoma

Opinion
Video

An expert on urothelial carcinoma gives an overview of disease risk factors, patient diagnosis, and testing practices.

Case 1: A 72-Year-Old Man with Metastatic Urothelial Carcinoma

Initial Clinical Presentation: 

  • A 72-year-old man presented to the clinic with complaints of dizziness and hematuria.
  • PMH: Obesity (BMI) and poorly controlled type 2 diabetes (blood sugar, 200 mg/dL)
  • SH: Patient does not smoke and occasionally drinks, in social settings.

Initial Clinical Workup: 

  • CT of 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)
  • Biopsy/pathology confirmed stage IV metastatic urothelial carcinoma
  • Molecular testing: FGFR2/3 mutation and fusionnegative

Initial Treatment and Disease Progression:

  • Patient received platinum-based chemotherapy with cisplatin.
    • Experiences platinum-based peripheral neuropathy (paresthesia) that interrupted the patient’s quality of life.
      • Neuropathy was low grade AE (Grade 1)which improved to Grade 0 with supportive care.
    • Partial response after 4 cycles of cisplatin; ECOG PS 1
    • Imaging showed no growth of existing lesions or new lesions after 4 cycles ​
  • Followed with IO maintenance with avelumab 800 mg IV infusion over 60 minutes every two weeks.
    • Following 9 cycles, patient achieved partial response in the lung and bladder.
    • Liver function tests, CrCl, and other labs were within normal limits
    • No infusion reactions
    • 5 months later, disease progression is confirmed
  • Patient was initiated on sacituzumab govitecan 10 mg/kg on Days 1 and 28 for 21-day continuous treatment cycle.
    • Patient experiences grade 3 neutropenia at the time of schedule treatment.
    • Delay dosing by 2 weeks until recovery to less than grade 1. Managed with 25% dose reduction and administration of G-CSF.

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 emphasized that urothelial carcinoma can arise anywhere along the urinary tract, including the upper tracts (renal pelvis), ureters, bladder, and proximal urethra. Although there may be some molecular differences between upper and lower tract tumors, advanced/metastatic disease is generally grouped together. Patients most commonly present with hematuria, but can have localized or metastatic symptoms depending on disease extent. Tobacco smoking is the classic risk factor, but other exposures and germline genetics can contribute.

Dr. Tagawa stated that all urothelial carcinoma patients warrant discussion of germline genetic testing, particularly to screen for Lynch syndrome in upper tract disease per guidelines. However, emerging data suggests lower tract tumors may also have relevant germline alterations. Additionally, next-generation sequencing of tumor tissue to assess somatic mutations is important, using a platform that can detect both DNA mutations and gene fusions. Common relevant alterations include FGFR3 activating mutations and FGFR2 fusions.

For systemic therapy decision-making, Dr. Tagawa emphasized considering cancer location/symptoms, germline and tumor genomic analysis, and patient factors impacting treatment eligibility/tolerance. Cisplatin eligibility is particularly important in urothelial carcinoma. This is determined by renal function, performance status, ability to tolerate intravenous fluids, baseline neuropathy, and hearing status. If cisplatin-ineligible, carboplatin-based regimens may be options, but response rates are lower than cisplatin-based chemotherapy.

In conclusion, Dr. Tagawa highlighted key considerations in evaluation and treatment decisions for advanced urothelial carcinoma: 1) disease extent, 2) genomic profiling of both germline and tumor, and 3) patient factors determining therapy eligibility and tolerance. As research continues, molecular analysis and precision therapy selection will likely play increasing roles in personalized management.

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

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