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SAN ANTONIO -- Extended compared with standard lymphadenectomy at the time of radical cystectomy provided no survival benefit to patients with muscle-invasive bladder cancer (MIBC), according to a phase III trial.

With a median follow-up of 6.1 years in both arms in the study, there was no significant difference between patients who underwent extended versus standard lymphadenectomy in terms of disease-free survival (HR 1.10, 95% CI 0.86-1.40, P=0.40) or overall survival (HR 1.13, 95% CI 0.88-1.45), reported Seth P. Lerner, MD, of the Baylor College of Medicine in Houston.

"And this was with extended long-term follow-up during a period of time when you would expect to see the vast majority of these events," Lerner said during a plenary session at the American Urological Association annual meeting.

Extended lymphadenectomy was also associated with greater morbidity, as well as higher perioperative mortality.

"Most importantly, there was an increase in mortality both at 30 days (2.7% vs 0.3%) and 90 days (6.5% vs 2.4%), in the extended arm versus the standard arm," Lerner reported. "This did include some patients who progressed, but when you take those out this difference persists."

"There is no indication of DFS or OS with long-term follow-up," Lerner said. "There is clearly a higher rate of high-grade adverse events [AEs] and mortality in the extended arm, so we have to communicate this to our patients when we are considering that."

The objective of SWOG S1011 was to test the hypothesis that extended lymphadenectomy is associated with improved DFS and OS compared to standard lymphadenectomy in patients with localized MIBC undergoing radical cystectomy. Lerner and colleagues hypothesized that patients in the extended arm would have a 10% improvement in 3-year DFS compared to an estimated 55% for patients in the standard arm (HR 0.72).

The trial was conducted at 27 sites in the U.S. and Canada, and randomized 292 patients to the extended lymphadenectomy arm and 300 to the standard arm.

Patients had a median age of 69, 21% were female, and 9% non-White. Clinical stage was balanced in both arms: T2 (71%) and T3-4a (29%). Neoadjuvant chemotherapy was given to 57% of patients in both arms.

All patients underwent a standard bilateral pelvic lymphadenectomy, including external and internal iliac and obturator lymph nodes. If randomized to the experimental arm, additional, extended lymphadenectomy up to at least the aortic bifurcation -- - including common iliac, pre-sciatic, and pre-sacral nodes -- was performed.

Lerner reported that, as expected, the number of lymph nodes removed was higher in the extended arm (39 vs 24), but that the incidence of pelvic lymph node metastasis pathologically proven was similar between the two arms (24% in the standard arm and 26% in the extended arm).

The operative time was longer in the extended arm at a median of 5.9 versus 5.3 hours.

Regarding AEs, there was a higher incidence of grade ≥3 sepsis, wound complications, ileus, thrombotic events, and additional surgical procedures in the extended arm.

In the extended arm, investigators reported 29 total venous thromboembolism events versus 18 in the standard arm.

There was no association of operative time or length of stay with DFS, OS, or grade 3-5 AEs, and no association of urinary diversion with grade 3-5 AEs.

"Higher accruing sites -- for some odd reason -- had a higher rate of grade 3-5 AEs," Lerner added.

There was a slightly higher rate of overall recurrence events in the extended arm (26.7% vs 23.7%). Local recurrence was also increased in the extended arm (12.7% vs 8.7%), but there was no difference in distant events (17.1% vs 18%).

Why was there no added benefit to extended lymphadenectomy?

Lerner noted that his group had assumed a 55% 3-year DFS rate and 5-year OS rate in the standard lymphadenectomy arm based on a review of published data at the time the trial was initiated. The true estimated 3-year DFS and 5-year OS rates were 62% and 63%, respectively, "so there was clearly a lower event rate," he observed.

Lerner also pointed out that the DFS and OS retrospective data came from the pre-neoadjuvant chemotherapy adoption era, whereas in this trial, neoadjuvant chemotherapy was given to more than half of the patients.

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