Completing Perioperative MIBC Therapy: Toxicity, ctDNA, and Teamwork

In this video, Roger Li, MD, discusses what happens after cystectomy and what it will take for patients to receive the full benefit of perioperative therapy.

Li says many questions about the adjuvant phase remain outstanding and are the focus of ongoing research. Enfortumab vedotin-ejfv (Padcev) carries substantial toxicity, particularly with long-term use, and for a patient who has achieved a pCR and converted to negative ctDNA, he says the open question is whether any adjuvant treatment is needed, let alone a combination as toxic as enfortumab vedotin plus pembrolizumab (Keytruda). He views VOLGA (NCT04960709) as a critical step toward an answer, and says these questions should be resolved in clinical trials with patient safety as the top priority.

Although urologists have not traditionally delivered these drugs, Li argues they play just as important a role as medical oncologists in recognizing toxicities. As surgeons, he notes, they are the only ones who can determine whether it is safe to proceed to surgery given lingering complications. He encourages urologists to learn to recognize these toxicities, draw on medical oncologists' experience, and act as a team.

On using ctDNA or pathologic response to tailor adjuvant therapy, Li cautions that differences in regimens, ctDNA patterns, and testing time points across trials mean the current evidence is not yet definitive. Until it is, he recommends staying as close as possible to the regimens as tested.

Asked for the single most important change, Li points to multidisciplinary care. Moffitt has followed that model for years, he says, but many community urologists still take patients to upfront cystectomy. Although earlier evidence suggested radical cystectomy alone could cure some patients, the improved outcomes from these trials mean it “behooves all of us” to refer patients to medical oncology for neoadjuvant treatment before surgery.