Dr Ghoreifi on the Feasibility for Consolidative Surgery After Enfortumab Vedotin/Pembrolizumab in Advanced Urothelial Cancer

We should discuss with the patient that we will revisit this [surgical] option and refer them to a urologist to obtain a second opinion about the possibility of surgery after receiving first-line immunotherapy."

Alireza Ghoreifi, MD, a urologic oncologist in the Department of Urology at Duke University, discussed the feasibility of consolidative surgery for patients with advanced urothelial cancer receiving frontline pembrolizumab (Keytruda) plus enfortumab vedotin-ejfv (Padcev).

Findings from a retrospective cohort study presented by Ghoreifi and colleagues at the 2025 AUA Annual Meeting showed that among patients with advanced bladder cancer or high-risk upper tract urothelial carcinoma who underwent consolidative surgery after receiving pembrolizumab plus enfortumab vedotin, the complete pathologic response (T0) rate was 60%.

Historically, patients with locally advanced or metastatic urothelial cancer have been considered unresectable and ineligible for surgery. However, Ghoreifi explained that this classification should be viewed as dynamic. Imaging assessments performed prior to treatment initiation, and serially every 3 months during treatment, often reveal significant tumor responses that may convert previously unresectable disease into surgically resectable cases.

Ghoreifi emphasized that even if patients are deemed inoperable at diagnosis, immunotherapy could shift their clinical status. Ongoing multidisciplinary evaluation is critical, and discussions about potential future surgery should be initiated early in the treatment course. Timely referral to a urologist for re-evaluation after systemic therapy is recommended to ensure optimal surgical planning if surgical candidacy changes.

He explained that factors to consider when identifying candidates for consolidative surgery following pembrolizumab plus enfortumab vedotin include treatment response on imaging, patient comorbidities, functional status, and the overall feasibility of major surgery. Ghoreifi noted that durable responses to immunotherapy may signify favorable tumor biology, supporting the rationale for pursuing definitive local control when possible.

The broader implications of these observations suggest that expanding the role of surgery in the management of advanced urothelial carcinoma could enhance long-term outcomes for select patients. Ghoreifi stressed that a flexible, individualized approach is needed, with reassessment at defined intervals based on radiographic response.