Case Presentation of a 62-Year-Old Man with a 3.5 cm Left Lateral Wall Bladder Tumor

Sima P. Porten, MD, MPH, FACS, Associate Professor of Urology, University of California, San Francisco, San Francisco, California, presents a complex bladder preservation case highlighting rising circulating tumor DNA in the absence of radiographic or pathologic recurrence, prompting debate regarding surveillance versus systemic therapy. A 62-year-old man with diet-controlled diabetes, hyperlipidemia, and minimal remote smoking history presented with a 3.5 cm left lateral wall tumor. Transurethral resection demonstrated high-grade muscle-invasive urothelial carcinoma. After counseling, the patient elected bladder preservation. Repeat transurethral resection and bladder biopsies, including prostatic urethra, showed no residual disease and no carcinoma in situ. He received concurrent cisplatin with radiation over six weeks and achieved no evidence of disease. Approximately 1 year later, circulating tumor DNA (ctDNA) began to rise, while computed tomography urography, chest imaging, fibroblast activation protein inhibitor positron emission tomography, pelvic magnetic resonance imaging, repeat transurethral resection of the scar, and cytology remained negative. The case raised the central question of whether rising ctDNA alone justifies systemic treatment. Panel discussion emphasized uncertainty regarding the source of ctDNA, whether localized or distant, and the absence of a validated threshold defining actionable recurrence. False positives cannot be excluded. Concerns were raised that initiating systemic therapy could commit the patient to prolonged treatment without a proven survival benefit in this setting. Options discussed include continued surveillance, adjuvant immunotherapy extrapolated from prior trials, or enfortumab vedotin plus pembrolizumab in the contemporary era. Radiation planning review was highlighted as critical to ensure adequate nodal coverage and target dosing, drawing parallels to biochemical recurrence management in prostate cancer. The discussion underscores the lack of definitive data guiding management of isolated ctDNA positivity after bladder preservation and the need to individualize decisions based on patient preference, risk tolerance, and evolving evidence. Don't forget to join the GRU Community: https://grandroundsinurology.com/regi... Follow us on Twitter/X: https://x.com/GRUrology And like and subscribe to us here on YouTube!