Final results from the SWOG S1011 randomized Phase III clinical trial, published in the New England Journal of Medicine, indicate that extended lymphadenectomy does not provide a significant survival benefit compared to standard lymphadenectomy in patients undergoing surgery for localized muscle-invasive bladder cancer. The extended procedure was also associated with increased complications and mortality within three months post-surgery.
The trial, led by Seth P. Lerner, MD, of Baylor College of Medicine, involved 592 patients with localized muscle-invasive bladder cancer from sites in the United States and Canada. Patients were randomized during surgery to undergo either bilateral standard lymphadenectomy (n = 300) or extended lymphadenectomy (n = 292), which included removal of common iliac, presciatic, and presacral nodes. 57% of patients in each group had received neoadjuvant chemotherapy. The primary outcome was disease-free survival.
Key Findings on Survival
After a median follow-up of 6.1 years, the 5-year disease-free survival rate was 56% in the extended lymphadenectomy group and 60% in the standard lymphadenectomy group (HR = 1.10, 95% CI = 0.86–1.40, P = 0.45). Overall survival rates at 5 years were 59% with extended lymphadenectomy and 63% with standard lymphadenectomy (HR = 1.13, 95% CI = 0.88–1.45), indicating no statistically significant difference between the two approaches.
Increased Adverse Events
The study also revealed a higher incidence of adverse events in the extended lymphadenectomy group. Grade 3 or higher adverse events were reported in 54% of patients undergoing extended lymphadenectomy compared to 44% in the standard lymphadenectomy group. The most common adverse events included anemia (15% vs 18%), urinary tract infection (9% vs 9%), and sepsis (7% vs 5%). Notably, death within 90 days after surgery occurred in 19 patients (7%) in the extended lymphadenectomy group and 7 patients (2%) in the standard lymphadenectomy group.
Implications for Clinical Practice
According to the researchers, the results suggest that extended lymphadenectomy should not be routinely performed in patients with muscle-invasive bladder cancer undergoing radical cystectomy. The findings support the adoption of bilateral standard lymphadenectomy as the standard of care for these patients. "Bilateral pelvic lymphadenectomy is an essential component of radical cystectomy as it provides local control, accurately identifies pathologic nodal metastases, and is associated with long-term disease-free survival for some patients with proven nodal metastases," said Dr. Lerner.
The study authors emphasize the importance of conducting prospective clinical trials to evaluate surgical procedures before their widespread adoption. The SWOG S1011 trial, along with similar trials in other cancer types, underscores the need for evidence-based approaches to surgical oncology.
