Extended Lymph Node Dissection Offers No Additional Benefit in Muscle-Invasive Bladder Cancer

Why Is Lymphadenectomy Important in Muscle-Invasive Bladder Cancer?

Muscle-invasive bladder cancer (MIBC) is an aggressive disease that has invaded the bladder's muscle layer and has serious clinical consequences. Radical cystectomy (surgical removal of the bladder) plays an important role in treatment. Removing lymph nodes, or lymphadenectomy, during surgery is common practice to control cancer spread, but the extent of removal is debated. Is standard or extended lymphadenectomy more effective? A new study addressing this question found that extended dissection does not offer the expected benefits and may carry a greater risk of complications.

Study Scope: Comparing Extended and Standard Lymphadenectomy

On October 2, 2024, The New England Journal of Medicine published this phase 3 trial (NCT01224665), which examined whether extended lymphadenectomy offered a survival advantage over standard dissection in patients undergoing radical cystectomy for MIBC. It included 592 eligible patients, all diagnosed with T2-T4a MIBC.

Patients were divided into standard lymphadenectomy (300 patients) and extended lymphadenectomy (292 patients) groups.

Study Design

In this phase 3 study, patients with localized T2 to T4a MIBC (with 2 or fewer positive lymph nodes) were randomly assigned during surgery in a 1:1 ratio to two groups:

• Standard Lymphadenectomy Group: Removal of lymph nodes on both sides of the pelvis.
• Extended Lymphadenectomy Group: A more extensive dissection removing common iliac, presiatic, and presacral lymph nodes in addition to standard dissection.

Patients were stratified by neoadjuvant chemotherapy use, tumor stage (T2 or T3-T4a), and Zubrod performance status score (0-1 or 2).

• Total Patient Number: 658 patients were enrolled; 592 were eligible and randomized.
• Surgical Procedures: Operations were performed by 36 surgeons at 27 centers in the United States and Canada.
• Follow-Up: Median follow-up was 6.1 years.
• Median Number of Nodes Removed: 24 in the standard group and 39 in the extended group.

Five-Year Disease-Free and Overall Survival Rates: No Difference

The results showed that extended lymphadenectomy did not improve disease-free survival (DFS) or overall survival (OS).

• Estimated 5-year disease-free survival was 60% with standard dissection and 56% with extended dissection (HR: 1.10; 95% CI: 0.86-1.40; P = .45).
• Similarly, estimated 5-year overall survival was 63% in the standard group and 59% in the extended group (HR: 1.13; 95% CI: 0.88-1.45). These differences were not statistically significant.

The Role of Adjuvant and Neoadjuvant Chemotherapy

The study also examined whether preoperative neoadjuvant chemotherapy affected survival outcomes. No survival difference by dissection type was observed among patients receiving neoadjuvant chemotherapy either. This indicates that choosing extended lymphadenectomy as a more aggressive strategy offers no additional benefit.

Adverse Effects: Greater Risk with Extended Lymphadenectomy

Extended lymphadenectomy carries a higher risk of perioperative morbidity and mortality than standard dissection. Severe adverse events (grade 3 or higher) occurred in 44% of the standard group and 54% of the extended group. The most common were anemia (18% versus 15%), urinary tract infection (9% in both groups), sepsis (5% versus 7%), wound complications (4% versus 5%), and venous thromboembolic events (3% versus 4%).

Within 30 days after surgery, 1 patient in the standard group and 8 in the extended group died. Within 90 days, 7 patients in the standard group and 19 in the extended group died. Most deaths were due to postoperative complications, although 2 in the standard group and 5 in the extended group resulted from disease progression.

Conclusion: Extended Lymphadenectomy Adds Risk Without Benefit

This study shows that extended lymphadenectomy does not improve survival in MIBC and increases complication risk. Standard dissection offers similar survival with lower morbidity and mortality, making it the safer option. These findings provide important guidance on surgical extent in MIBC and emphasize the need to reconsider routine extended lymphadenectomy.