Extended lymphadenectomy in patients undergoing radical cystectomy for clinically localized muscle-invasive bladder cancer was not associated with improved disease-free survival or overall survival and may increase the risk of adverse events and postsurgical mortality, according to new findings presented by Lerner et al at the 2023 ASCO Annual Meeting (Abstract 4508).
Background
Once cancer invades the muscle of the bladder, it can also enter the bloodstream and lymphatic system and can lodge in the lymph nodes. In approximately 25% of patients with muscle-invasive bladder cancer, the disease has already spread to regional lymph nodes.
As a result, after removing the bladder in these patients, surgeons will also remove all of the lymph nodes in the primary area around the bladder. Removing those lymph nodes may significantly reduce the risk of cancer recurrence within the pelvis. An extended lymphadenectomy involves the removal of additional lymph nodes beyond the extent of the standard procedure.
“Extended lymphadenectomy is considered a standard of care and is increasingly used, especially for patients with locally advanced bladder cancer who have a higher risk of lymph node metastases,” explained lead study author Seth P. Lerner, MD, Professor of Urology, the Beth and Dave Swalm Chair of Urologic Oncology, and Director of Urologic Oncology and the Multidisciplinary Bladder Cancer Program at the Baylor College of Medicine and Chair of the Local Bladder Cancer Committee at the Southwest Oncology Group (SWOG) Cancer Research Network.
Study Methods and Results
In the new phase III SWOG S1011 clinical trial, researchers enrolled 658 patients—618 of whom were eligible to be randomly assigned to receive either extended or standard lymphadenectomy—and recruited 36 surgeons, who were required to undergo a credentialing process designed specifically for the study. The researchers then examined whether the patients benefited from extended lymphadenectomy to remove even more lymph nodes from a wider area and whether this would reduce the risk of recurrent disease or mortality.
The patients involved in the trial were randomly assigned during their surgery, after the surgeon had determined that the disease had not metastasized beyond the pelvis. All of the patients underwent a standard bilateral pelvic lymphadenectomy; however, those randomly assigned to the investigative arm also underwent an extended lymphadenectomy, with nodes removed at least up to the aortic bifurcation.
Compared with those in the control group, patients in the extended lymphadenectomy group had a median of 39 nodes vs 24 nodes removed, but the percentage of nodes found to contain metastatic disease was similar in both groups at 26% vs 24%, respectively.
The researchers hypothesized that the patients in the extended lymphadenectomy group would experience improved disease-free and overall survival compared with those in the control group. However, no significant statistical differences were observed between the two groups in disease-free survival (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 0.87–1.42, two-sided P = .40) or overall survival (HR = 1.15, 95% CI = 0.89–1.48, two-sided P = .29).
Further, 49% of patients in the extended lymphadenectomy group experienced grade 3 or 4 adverse events within 90 days of surgery, regardless of attribution, compared with 42% of patients in the control group. The researchers also reported that the number of deaths within 90 days of surgery was greater in the extended lymphadenectomy group (19 vs 7 patients).
Conclusions
The researchers noted that a definitive phase III surgical trial of this sort was an ideal fit for the National Cancer Institute’s National Clinical Trials Network (NCTN).
“SWOG S1011 addressed an important surgical question, and the federally funded NCTN is uniquely suited for such practice-changing trials led by surgical oncologists,” Dr. Lerner highlighted. “Collaboration across the NCTN was the key to success, as was equipoise from high-volume surgeons who recognized the lack of level I evidence supporting our current practice at the time we conceived the trial,” he concluded.
The researchers anticipate that the results of their new study may change clinical practice in treating patients with muscle-invasive bladder cancer.
Disclosure: The research in this study was supported by the National Cancer Institute and the Canadian Cancer Society. For full disclosures of the study authors, visit meetings.asco.org.
