Editorial Note: Radical cystectomy (RC) and pelvic lymph node dissection (PLND) are standard treatments for muscle-invasive bladder cancer (MIBC), yet distant metastasis remains a challenge for some patients. Exploring perioperative treatment options for MIBC is crucial to improve patient outcomes. At the 39th Annual European Association of Urology (EAU24) Congress in Paris, France, “Oncology Frontier” invited Dr. Zedan Zhang from Professor Kan Gong’s team at Peking University First Hospital to discuss the latest advancements in MIBC perioperative treatment.
Oncology Frontier: The CheckMate274 study has ushered in the era of adjuvant immunotherapy for MIBC. Can you provide an overview of the current research landscape for perioperative treatment of MIBC?
Professor Kan Gong and Dr. Zedan Zhang: In recent years, research on MIBC has made significant breakthroughs. The POUT study established the GC regimen (gemcitabine + cisplatin) as the standard for adjuvant treatment of upper tract urothelial carcinoma. The CheckMate274 study is the first phase 3 study with positive results for adjuvant immunotherapy in MIBC, showing that nivolumab significantly improves disease-free survival (DFS) (22.0 vs. 10.9 months, HR 0.70). Recently, the phase 3 KEYNOTE-123 study also achieved its primary endpoint, with pembrolizumab significantly extending DFS (HR 0.7) and overall survival (OS) (HR 0.59). Beyond adjuvant therapy, neoadjuvant immunotherapy and bladder-sparing treatments are also current research hotspots in perioperative treatment.
Oncology Frontier: What are the latest research findings on perioperative treatment for MIBC presented at this EAU conference?
Professor Kan Gong and Dr. Zedan Zhang: At EAU24, the phase 2 NURE-Combo study (abstract A0901) included 31 MIBC patients (cT2-T4a, N0-1, M0) ineligible for cisplatin-based therapy. Patients received four cycles of neoadjuvant nivolumab and nab-paclitaxel followed by radical cystectomy and 13 cycles of adjuvant nivolumab. The primary endpoint was the pathological complete response (pCR, ypT0N0) rate. Results showed a pCR rate of 38%, with a 12-month event-free survival (EFS) rate of 96.4%. All responders had negative ctDNA after neoadjuvant therapy. The regimen was well-tolerated, with only four patients (14.8%) unable to complete the full neoadjuvant treatment due to treatment-related adverse events (TRAEs), and four patients experiencing grade 3 TRAEs. This study preliminarily confirms that the neoadjuvant nivolumab + nab-paclitaxel followed by adjuvant nivolumab is a safe and effective perioperative treatment strategy, pending further validation with larger sample sizes.
Chinese researchers also reported a single-arm study (abstract A0904) on tislelizumab combined with the GC regimen (gemcitabine + cisplatin) as neoadjuvant therapy. Fourteen out of fifteen patients completed 3-4 cycles of neoadjuvant therapy and radical surgery. Five patients (50%) achieved pCR (ypT0N0), nine patients (64.2%) experienced downstaging (ypT2N0), and eleven patients (78.5%) had complete lymph node responses (pN0). One patient discontinued tislelizumab due to adverse events.
Oncology Frontier: Cisplatin intolerance is a major limitation for systemic treatment in bladder cancer patients, necessitating kidney function evaluation. Could you discuss the safety management of perioperative treatments based on the latest findings from the EAU conference?
Professor Kan Gong and Dr. Zedan Zhang: A multicenter study by the EAU Young Academic Urologists Urothelial Cancer Working Group (abstract A0143) explored the optimal method for kidney function evaluation for cisplatin-based neoadjuvant chemotherapy in MIBC. Among 956 patients, different equations—CG, MDRD, CKD-EPI, and non-race CKD-EPI—found 30.0%, 33.3%, 31.9%, and 27.7% of patients ineligible for cisplatin, respectively (P=0.052). Consistency evaluations among these eGFR formulas showed basic agreement (Cohen’s kappa: 0.66-0.95). For 245 patients with measured creatinine clearance (CrCl), only 37 (15.1%) had CrCl <60 mL/min. Agreement between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40), with all eGFR formulas significantly underestimating measured CrCl. Notably, for patients with eGFR 40-59 mL/min, 78%-87.5% had measured CrCl ≥60 mL/min.
This study indicates that all eGFR formulas yield similar cisplatin ineligibility rates (around 30%), yet many patients are actually cisplatin-tolerant based on measured CrCl, especially those with eGFR 40-59 mL/min. Cisplatin’s primary concern is nephrotoxicity, along with bone marrow suppression and gastrointestinal symptoms, all of which have established clinical management protocols. With the integration of immunotherapy, targeted therapy, and antibody-drug conjugates in perioperative settings, further assessment of these new treatments’ safety profiles is essential for comprehensive perioperative safety management.
Professor Kan Gong
- Deputy Director, Urology Research Institute, Peking University
- Chief Physician, Professor, Doctoral Supervisor
- Recipient of the Third Batch of “National High-level Talent Special Support Plan (Ten Thousand Talent Program)”
- Vice Chairman, Chinese Medical Promotion Association Urology Branch
- Member, Tumor Group, Chinese Medical Association Urology Branch
- Member, Rare Diseases Branch, Chinese Medical Association
- Member, Urological Tumor Committee, Chinese Medical Doctor Association
- Editor, “Chinese Guidelines for the Diagnosis and Treatment of Urological Diseases – Prostate Cancer”
Dr. Zedan Zhang
- PhD candidate in Urology at Peking University First Hospital
- Visiting Scholar at Stanford University
- Published 25 papers in international journals, including 9 as first/co-first author, 5 in Q1 journals
- Participated in 7 national/provincial projects
- Presented orally and through posters at EAU and Chinese Urology conferences
- Recipient of the Best Poster Award at the First Chinese Medical Association Rare Diseases Branch Conference
- Recipient of the National Scholarship for Graduate Students and Beijing University Excellent Student Award.
