In a multicentre, randomised, controlled, phase III SWOG S1011 study involving patients with localised muscle invasive bladder cancer undergoing radical cystectomy, extended lymphadenectomy did not result in improvement in disease-free survival (DFS) or overall survival (OS) as compared with standard lymphadenectomy.
Moreover, extended lymphadenectomy was associated with greater morbidity and higher perioperative 90-day mortality than standard lymphadenectomy. The findings are reported by Dr. Seth P. Lerner of the Scott Department of Urology, Baylor College of Medicine Medical Center in Houston, TX, US, and colleagues on 2 October 2024 in The New England Journal of Medicine.
The authors wrote in the background that bilateral pelvic lymphadenectomy is an essential component of radical cystectomy because it provides local control, aids in the accurate identification of pathologic nodal metastases, and is associated with long-term DFS among some patients with proven nodal metastases. Despite a lack of data from randomised studies to confirm a benefit with more extensive lymphadenectomy, many academic centres have adopted this approach, with a minimum number of approximately 25 lymph nodes as a surrogate for extended dissection being proposed to serve as a quality-assurance measure.
In the SWOG S1011 study, the researchers randomly assigned, in a 1:1 ratio, patients with localised muscle invasive bladder cancer of clinical stage T2 to T4a with two or fewer positive nodes (N0, N1, or N2) to undergo bilateral standard lymphadenectomy or extended lymphadenectomy involving removal of common iliac, presciatic, and presacral nodes.
Randomisation was performed during surgery and stratified according to the receipt and type of neoadjuvant chemotherapy, tumour stage (T2 versus T3 or T4a), and a Zubrod’s performance status score (0 or 1 versus 2). The primary outcome was DFS; OS and safety were also assessed.
Of 658 patients who were enrolled, 592 eligible patients were randomly assigned to undergo extended lymphadenectomy (292 patients) or standard lymphadenectomy (300). Surgery was performed by 36 surgeons at 27 sites in the US and Canada. Neoadjuvant chemotherapy had been received by 57% of the patients.
At a median follow-up of 6.1 years, recurrence or death had occurred in 130 patients (45%) in the extended lymphadenectomy group and in 127 patients (42%) in the standard lymphadenectomy group. The estimated 5-year DFS was 56% and 60% (hazard ratio [HR] for recurrence or death 1.10, 95% confidence interval [CI] 0.86 to 1.40; p = 0.45).
At 5 years, OS was 59% in the extended lymphadenectomy group and 63% in the standard lymphadenectomy group (HR for death 1.13, 95% CI 0.88 to 1.45).
Adverse events of grade 3 to 5 occurred in 157 patients (54%) in the extended lymphadenectomy group and in 132 patients (44%) in the standard lymphadenectomy group; death within 90 days after surgery occurred in 19 patients (7%) and 7 patients (2%), respectively.
Muscle invasive bladder cancer is a heterogeneous disease, and the results of this study apply only to patients with predominant urothelial histologic features, clinical stage T2 to T4a disease with two or fewer positive nodes, and an intraoperative exploration that ruled out disease in the extended template. The patient population was predominantly non-Hispanic White (90%), and the median age of the patients was slightly younger than that of persons with localised invasive and in situ cancer. The study team did not allow robotic surgery.
The incidence of serious adverse events and 90-day mortality were higher in the extended lymphadenectomy group than in the standard lymphadenectomy group, the findings that further support standard over extended lymphadenectomy. The authors commented that their study was conducted during the time that Enhanced Recovery after Surgery (ERAS) protocols were being adopted and they did not collect data on use of ERAS protocols other than preoperative and postoperative anticoagulation, which were widely considered to be the standard-of-care before the inception of this study. Broader adoption of ERAS protocols may reduce the risk of adverse events of grade 3 to 5 that are associated with radical cystectomy and pelvic lymphadenectomy.
The study was supported by grants from the US National Cancer Institute of the National Institutes of Health and the Canadian Cancer Society.
Reference
Lerner SP, Tangen C, Svatek RS, et al. for the SWOG S1011 Trial Investigators. Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer. N Engl J Med 2024;391:1206-1216.