Early Mutation Profiling in Urothelial Cancer: A Path to Targeted Therapy

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Arlene Siefker-Radtke, MD, emphasizes the importance of early mutation profiling in metastatic urothelial cancer and highlights the potential for targeted agents and clinical trials to improve treatment outcomes.

Transcript:

Arlene O. Siefker-Radtke, MD: We are often seeing patients who have had prior treatment or even referrals from urology coming in with mutation profiles in hand. Personally, I think this is quite wonderful. I believe we should test for these mutation profiles very early in a patient’s disease, especially the moment they have metastatic or incurable urothelial cancer since we have targeted agents that target FGFR3 mutations and we also have many clinical trials targeting novel mutations that may be present on a patient’s tumor.

There [are] also trials studying FGF-targeted therapy in the neoadjuvant or adjuvant spaces and in superficial bladder cancer. So our urologic oncology colleagues are gaining an interest in novel targeted strategies as well. We currently have an approval with pembrolizumab for superficial bladder cancer patients, and patients have been referred to medical oncologists like myself, and potentially you as well, for treatment with an immune checkpoint inhibitor. So I think it’s very important to have a close tie and play a tight role with our urologic oncology colleagues who do the surgeries as patients will need frequent monitoring of the urothelium, and we may see additional targeted agents approved in earlier-stage disease.

Transcript is AI-generated and edited for clarity and readability.

Case: A 73-Year-Old Man with Metastatic Urothelial Carcinoma

Initial Clinical Presentation:

  • A 73-year-old man presented to you from their local urologist with dizziness and hematuria
  • PMH: hypertension and diabetes (uncontrolled)
  • SH: former smoker; consumes alcohol 2-3 times per week
  • Chest x-ray and CT revealed a 3.7-cm mass on the right lateral wall of the bladder and liver metastases
  • Cystoscopic biopsy/pathology confirmed stage IV urothelial carcinoma
  • ECOG PS 1
  • CrCl 65 mL/min
  • The patient received gemcitabine + cisplatin (6 cycles)
    • Partial response at completion of chemotherapy
    • No maintenance therapy given, although discussed with patient

Current Clinical Presentation:

  • 7 months later, disease progression was discovered on routine follow up imaging

Treatment:

  • The patient received pembrolizumab and a partial response was achieved at 6 cycles
  • Molecular testing showed no FGFR2 mutation or fusion
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