Professor Powles predicts a significant shift in bladder cancer treatment. High pathological complete response rates with neoadjuvant EV Pembro may allow responders, identified by imaging and circulating tumor DNA, to safely avoid radical cystectomy, a life-altering surgery that may become unnecessary for many.
Professor Powles argues against treating isolated metastases in urothelial cancer with local therapies like surgery or radiation. He asserts that ctDNA data confirms the disease is fundamentally systemic, meaning a single visible metastasis likely indicates widespread micrometastatic disease, mandating aggressive systemic therapy first.
Professor Powles predicts that urinary tumor DNA (utDNA) will become the key biomarker for detecting local relapse in bladder-sparing strategies. He notes that blood-based ctDNA is poor at identifying non-muscle invasive disease, creating a clear and necessary role for utDNA to assess local risk and guide interventions more accurately.
Despite the temptation to shorten therapy for patients with good responses or toxicity, Professor Powles warns against deviating from the rigorous trial protocols that produced exceptional survival outcomes. He argues that de-escalation should be explored only within formal research studies to avoid compromising hard-won patient cures.
Professor Powles highlights a critical limitation of ctDNA in bladder cancer management. While excellent for assessing systemic risk, ctDNA may remain negative during a local, non-muscle invasive relapse (e.g., T1 cancer). This necessitates continued local surveillance like cystoscopy, even in ctDNA-negative patients pursuing bladder-sparing approaches.