Removing More Lymph Nodes May Not Improve Survival in Muscle-Invasive Bladder Cancer

Removing additional lymph nodes, as compared with standard removal of lymph nodes on both sides of the pelvis, did not improve disease-free or overall survival in patients with muscle-invasive bladder cancer who underwent a radical cystectomy, recent study findings demonstrated.

Results from the trial, which were published in The New England Journal of Medicine, also showed that extended lymphadenectomy (removal of common iliac, presciatic and presacral nodes) was associated with higher perioperative morbidity and mortality compared with standard lymphadenectomy (dissection of lymph nodes on both sides of the pelvis).

“The average number of lymph nodes removed at these [academic] centers is 20 to 30, and a minimum number of lymph nodes (approximately 25) as a surrogate for extended dissection has been proposed to serve as a quality-assurance measure for this operation,” the study authors wrote in the introduction.

In this trial, 592 patients with localized muscle-invasive bladder cancer were randomly assigned to undergo either extended lymphadenectomy (292 patients) or standard lymphadenectomy (300 patients). Of note, 57% of patients in the trial received neoadjuvant (first treatment given with the aim to shrink the tumor before the main treatment like surgery) chemotherapy, most of whom received cisplatin-based therapy.

During a median follow-up of 6.1 years, recurrence or death occurred in 130 patients (45%) assigned extended lymphadenectomy and in 127 patients (42%) assigned standard lymphadenectomy. The estimated five-year disease-free survival (the time after treatment when a patient with cancer survives without symptoms or signs of the disease) rate was 56% in the extended lymphadenectomy group and 60% in the standard lymphadenectomy group.

The first site of disease recurrence was local (a location near where the cancer began) in 35% of patients in the extended lymphadenectomy group compared with 23% in the standard lymphadenectomy group. Regarding distant recurrence (cancer that returns in another part of the body far away from its original location), this occurred in 51% of patients assigned extended lymphadenectomy and in 62% of those assigned standard lymphadenectomy. Both local and distant recurrences occurred in 11% in the extended lymphadenectomy group and in 12% in the standard lymphadenectomy group.

At five years, the rate of overall survival (the percentage of patients with cancer who are still alive after treatment) was 59% in patients assigned extended lymphadenectomy compared with 63% in those assigned standard lymphadenectomy.

Side effects considered grade 3 (severe) to grade 5 (causing death) occurred in 157 patients (54%) assigned extended lymphadenectomy versus 132 patients (44%) assigned standard lymphadenectomy. More patients in the extended lymphadenectomy group died within 90 days after surgery compared with those in the standard lymphadenectomy group (7% versus 2%).

To conduct this trial, researchers enrolled patients with localized muscle-invasive bladder cancer that that were clinical stages T2 (confined to the muscle) to T4a (invading adjacent organs) and with two or fewer positive lymph nodes. Several areas of interest throughout the study included disease-free survival, overall survival and safety.

Research into the correct approach for lymph node removal has been done in other cancer types.

“Randomized, phase 3 trials in endometrial, gastric and pancreatic cancers

have not shown improved survival with extended lymphadenectomy, contrary to what was expected, and among patients with gastric cancer, the incidence of surgery-related complications was higher with the more extensive lymphadenectomy than with standard extended regional lymphadenectomy,” study authors wrote.

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