Extended Lymphadenectomy Shows No DFS, OS Benefit During Radical Cystectomy in Urothelial Cancer

Treatment with concurrent radical cystectomy and extended lymph node dissection (ELND) did not show benefit in disease-free survival (DFS) or overall survival (OS) compared with standard lymph node dissection (SLND) alone in patients with muscle invasive urothelial cancer, according to data from a subgroup analysis of the phase 3 SWOG S1011 trial (NCT01224665) presented during the 2024 American Urological Association Annual Meeting.¹

At the 30-day mortality point, investigators reported 8 events in the ELND arm vs 1 event in the SLND. At the 90-day mortality point, there were 19 events in the ELND arm vs 7 events in the SLND arm.

“Importantly, there was an increase in mortality events both at 30 and 90 days in the extended arm vs the standard arm,” lead author Seth P. Lerner, MD, the Beth and Dave Swalm Chair in Urologic Oncology, Department of Urology, and professor of urology, Baylor College of Medicine, Houston, Texas, said during the presentation. “This included patients who had progressed, but when those patients were removed from the analysis, this difference persisted,” Lerner continued.

Investigators also noted that patients who received ELND had greater morbidity and higher perioperative mortality compared with patients who received SLND. They also reported longer surgical time, higher blood loss, higher number of progression events within 90 days, and a higher venous thromboembolism rate than for patients who received ELND.

In the SWOG S1011 trial, patients were randomly assigned to receive ELND (n = 303) or SLND (n = 315) after intraoperative exploration showed that they did not have disease outside the pelvis. In the ENLD arm, 11 patients were deemed ineligible resulting in an intent-to-treat cohort of 292 patients who received protocol surgery and were evaluated for adverse events (AEs). Patients in the experimental arm also received additional ELND up to at least the aortic bifurcation, including removal of the common iliac, presciatic, and presacral lymph nodes. In the SLND arm, 300 patients were determined to be the intent-to-treat cohort; AEs were also evaluated.

Prerandomization clinical covariates indicated that both arms experienced hydronephrosis: 27% of patients in the ELND arm (n = 292) compared with 25% of patients in the SLND arm (n = 300). An equal proportion of patients received neoadjuvant chemotherapy (57% for both arms). Further, the incidence of pathologically proven pelvic lymph node metastasis was similar between both arms, with the median of 2 positive nodes in the ELND arm (range, 1-35) reported and 1 positive node in the SLND arm (range, 1-16) reported.

Overall, there were a greater number of grade 3, grade 4, and grade 5 AEs in patients who received ELND compared with SLND. “There was a higher incidence of sepsis, wound complications, ileus, and thromboembolic events in the ELND arm,” Lerner said.

In the ELND arm, investigators reported 29 total venous thromboembolism (VTE) events vs 18 VTEs in the SLND arm. The majority of patients received VTE prophylaxis as a standard of care.

Variant histology had no impact on either DFS or OS rates but ileal conduit was associated with a worse DFS and OS likely because these were patients with more locally advanced disease, and about half of the patients received a neobladder, Lerner said.

“Blood transfusions were not associated with either DFS or OS and there was no association with operative time or length of stay with DFS, OS, or grade 3 to 5 AEs,” Lerner said.

Investigators reported a slightly higher rate of overall recurrence events in patients in the ELND arm (26.7%) vs the SLND arm (23.7%). Local recurrence was higher in the ELND arm (12.7%) vs the SLND arm (8.7%) but there was no difference between the arms regarding distant events (17.1% vs 18%, respectively). Neoadjuvant chemotherapy was also stratified by those who did or did not receive the treatment.

“In summary, patients undergoing radical cystectomy and extended node dissection had higher lymph node yield, similar pathologic T stage, and rate of nodal metastasis,” Lerner said. “There is no indication of a benefit of DFS or OS with long-term follow-up and there is clearly a higher rate of high-grade AEs and mortality in the extended arm, so we need to communicate that to our patients,” Lerner said.

Reference

Lerner SP, Tangen C, Svatek RS, et al. Subgroup analysis of the phase III surgical trial to evaluate the benefit of a standard versus an extended lymphadenetomy performed at the time of radical cystectomy for muscle invasive urothelial cancer. Presented at: 2024 American Urological Association Meeting; May 3-6, 2024; San Antonio, TX.