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urothelial carcinoma (transitional cell carcinoma)

See bladder cancer Tumor may also occur in the ureter or renal pelvis [3] Microscopic Pathology: Grading: WHO 1999 - papillary urothelial neoplasm of low malignant potential - low grade urothelial carcinoma, grade I - high grade urothelial carcinoma, grade II - high grade urothelial carcinoma, grade III Genetics: - implicated genes LYPD3, UBIAD1, TKT2 Laboratory: Immunocytochemistry: - carcinoembryonic antigen: positive - high molecular weight cytokeratin: positive - CK7: positive - CK20: positive - vimentin: negative Special laboratory: - cystoscopy (image) [6] Management: - chemotherapy: 3-week cycle for up to 8 cycles - cisplatin (70 mg/m2 on day 1), - gemcitabine (1000 mg/m2 on days 1 & 8) - bevacizumab (Avastin; 15 mg/kg on day 1) - vinflunine is not recommended (NGC, NICE) - pembrolizumab - patients not eligible for or who have failed cisplatin-containing chemotherapy [5] - survival benefit (~3 months) - adjuvant nivolumab after radical surgery - FDA-approved as adjuvant therapy regardless of prior neoadjuvant chemotherapy, nodal involvement, or PD-L1 status - adjuvant nivolumab improves disease-free survival in patients with muscle-invasive urothelial carcinoma with PD-L1 expression of >1% [9] - avelumab survival benefit (~7 months) [8] - gemcitabine + cisplatin (GC) 2 cycles, then GC + ipilimumab 4 cycles (1 year survival < 60% for metastatic disease [7]

Interactions

disease interactions

General

carcinoma urothelial neoplasm

Database Correlations

OMIM 109800

References

  1. Busch & Algaba. Virchows Arch 441:105-8, 2002
  2. Dabbs. Diagnostic Immunohistochemistry. Churchill-Livingstone, 2002. page 475
  3. Transitional Cell Cancer of the Renal Pelvis and Ureter (PDQ): Treatment http://www.nci.nih.gov/cancertopics/pdq/treatment/transitionalcell/HealthProfessional
  4. Management of transitional cell carcinoma of the bladder Scottish Intercollegiate Guidelines Network (SIGN) Corresponding NGC guideline withdrawn Jan 2011 http://www.sign.ac.uk/pdf/sign85.pdf
  5. Bellmunt A, de Wit R, Vaughn DJ et al Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017; 376:1015-1026. March 16, 2017 PMID: 28212060 Free full text http://www.nejm.org/doi/full/10.1056/NEJMoa1613683 - Bankhead C Survival Bump in Bladder Cancer with Keytruda. But no outcome advantage for Tecentriq in metastatic urothelial cancer. MedPage Today. Feb 11, 2018 https://www.medpagetoday.com/meetingcoverage/mgucs/71089 - Bellmunt J et al Two-year follow-up from the phase III KEYNOTE 045 trial of pembrolizumab vs investigators choice in recurrent, advanced urothelial cancer. Genitourinary Cancers Symposium (GUCS) 2018; Abstract 410.
  6. So C, Siddiqui MM (image) Urothelial Carcinoma. N Engl J Med 2018; 378:e8. Feb 1, 2018 PMID: 29385365 http://www.nejm.org/doi/full/10.1056/NEJMicm1709216
  7. Fuerst ML with critique by Bowman IA Metastatic Urothelial Cancer: 'PD-1/PD-L1 Inhibitors Poised to Impact Standard of Care'. Patients with tumors with mutations in genes involved in repairing DNA damage were most likely to respond. MedPage Today. ASCO Reading Room 06.14.2018 https://www.medpagetoday.com/reading-room/asco/immunotherapy/73490 - Galsky MD, Wang H, Hahn NM et al Phase 2 trial of gemcitabine, cisplatin, plus ipilimumab in patients with metastatic urothelial cancer and impact of DNA damage response gene mutations on outcomes. European Urology 2018; 73 (5): 751-759. PMID: 29248319 https://www.europeanurology.com/article/S0302-2838(17)31033-3/abstract
  8. Powles T et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Engl J Med 2020 Sep 18; [e-pub] PMID: 32945632 https://www.nejm.org/doi/10.1056/NEJMoa2002788
  9. Bajorin DF, Witjes JA, Gschwend JE Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med 2021; 384:2102-2114. June 3 PMID: 34077643 https://www.nejm.org/doi/full/10.1056/NEJMoa2034442
  10. Bassett M PD-1 Inhibitor OK'd as Adjuvant Therapy for Bladder Cancer. Nivolumab gets FDA approval for those at high risk of recurrence after surgery. MedPage Today August 20, 2021 https://www.medpagetoday.com/hematologyoncology/othercancers/94154