ctDNA MRD Guidance in Bladder Cancer: Pharmacy Specialist on NCCN Updates

The latest NCCN guideline updates for bladder cancer represent a hallmark shift toward highly personalized, precision-driven oncology, according to Kirollos Hanna, PharmD, BCPS, BCOP.¹ Clinicians can now look beyond standard imaging to assess patients at the molecular level post-radical cystectomy.

Historically, the 5-year overall survival (OS) rate for metastatic urothelial carcinoma has hovered between 5% and 10%. To maximize event-free survival (EFS), guidelines now incorporate minimal residual disease (MRD) guidance. Key data from the phase 3 IMvigor011 trial (NCT04660344) demonstrate that patients who remain ctDNA-positive after cytoreductive therapies, such as dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) or neoadjuvant enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) in muscle invasive bladder cancer (MIBC), which was recently approved by the FDA, benefit significantly from subsequent immunotherapy.^2,3 Specifically, transitioning these patients to adjuvant atezolizumab (Tecentriq) rather than active surveillance offers a crucial, evidence-based pathway to clear sub-visual disease and improve long-term outcomes.

Hanna is the director of Pharmacy at Minnesota Oncology, an assistant professor of Pharmacy at the Mayo Clinic Alix School of Medicine, and an editorial advisory board member of the journal ONCOLOGY®.

Transcript:

CancerNetwork: How might the most recent NCCN guideline update impact standard practice for patients who test positive on multiplex polymerase chain reaction (PCR) ctDNA MRD assays?

Hanna: We have seen a dramatic shift in the guideline updates in bladder cancer over the last several years. This is one of the hallmark shifts we have seen, where they are now utilizing MRD guidance to look at whether patients achieve a pathological complete response, to help guide subsequent treatment decision-making. When you look at the bladder cancer population, a lot of these patients are older, and when they reach the metastatic setting, despite significant updates, the 5-year OS for patients with locally advanced or metastatic urothelial carcinoma is still hovering between 5% and 10%. Our goal in non-muscle invasive bladder cancer [NMIBC] and even MIBC is to try to achieve the best event-free survival [EFS] we can.

Recently, there was an approval of enfortumab vedotin in combination with pembrolizumab that has been extended by the FDA as neoadjuvant treatment prior to surgery. It is exciting that after patients undergo some type of cytoreductive therapy—say, MVAC, or enfortumab vedotin plus pembrolizumab—they go on to radical cystectomy and pelvic lymph node dissection, and we can now assess them down to the cellular level rather than simply being unable to detect disease on imaging. What we have seen, which has driven these NCCN guideline updates, is that patients who do not achieve a negative ctDNA result should be put on some form of immunotherapy, specifically atezolizumab, because it is the one that is FDA-approved. Patients who go on to immunotherapy after not achieving a negative PCR have much higher EFS, based on findings from the [phase 3 IMvigor011 trial (NCT04660344)].

References

1. NCCN recommends ctDNA-MRD testing using Signatera technology in landmark bladder cancer guideline update. News release. Natera Inc. June 23, 2026. Accessed July 15, 2026. https://tinyurl.com/3u8vcr65
2. Powles T, Kann AG, Castellano D, et al. ctDNA-guided adjuvant atezolizumab in muscle-invasive bladder cancer. N Engl J Med. 2025;393:2395-2408. doi:10.1056/NEJMoa2511885
3. FDA approves pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph each with enfortumab vedotin-ejfv for muscle invasive bladder cancer. News release. FDA. July 10, 2026. Accessed July 15, 2026. https://tinyurl.com/3nmcpncy