Extended Lymphadenectomy Does Not Improve DFS/OS in Bladder Cancer

Disease-free survival and overall survival were lower with extended lymphadenectomy compared with standard lymphadenectomy.

Extended lymphadenectomy did not improve disease-free survival (DFS) or overall survival (OS) and was associated with higher levels of perioperative morbidity and mortality among patients with muscle-invasive bladder cancer undergoing radical cystectomy, investigators of the phase 3 SWOG S1011 trial (NCT01224665) found.

The estimated 5-year DFS rate was 56% for the extended lymphadenectomy group and 60% for the standard lymphadenectomy group(HR, 1.10; 95% CI, 0.86-1.40; P = .45). The estimated 5-year OS rate was 59% for the extended lymphadenectomy group and 63% for the standard lymphadenectomy group (HR, 1.13; 95% CI, 0.88-1.45).

At the median follow-up point of 6.1 years, death or recurrence had happened in 130 patients (45%) in the extended lymphadenectomy group and 127 patients (42%) in the standard lymphadenectomy group.

“…Extended lymphadenectomy did not result in improvement in [DFS] or [OS] as compared with standard lymphadenectomy,” the authors of the study wrote. “Moreover, extended lymphadenectomy was associated with greater morbidity and higher perioperative 90-day mortality than standard lymphadenectomy.”

The intention-to-treat population included 592 patients, 300 of whom were in the standard lymphadenectomy group and 292 were in the extended lymphadenectomy group. Assignment was randomized in a 1:1 ratio with the use of dynamic balancing based on clinical stage, performance status score, and receipt of neoadjuvant chemotherapy.

Standard lymphadenectomy was the removal of external and internal iliac and obturator nodes, and all potential lymph node–bearing tissue was to be removed within the boundaries. Extended lymphadenectomy included removal of the common iliac nodes on both sides, node-bearing tissue in the presciatic region, and presacral node. The node dissection could be extended up to the inferior mesenteric artery.

Patients who were eligible for enrollment had urothelial cancer of clinical stage T2 to T4a with 2 or fewer nodes with or without variant histologic subtypes and elected to undergo radical cystectomy with curative intent. Significant exclusion criteria were previous partial cystectomy, previous pelvic surgery obviating a complete extended lymphadenectomy, and an inability to perform a thorough pelvic lymph node dissection per surgeon discretion.

Patients were permitted to have completed neoadjuvant chemotherapy at least 70 days prior to enrollment. Those who had not taken neoadjuvant chemotherapy were recommended postoperative adjuvant chemotherapy for disease of any pathologic tumor stage with positive nodes or pathologic T3 or T4 disease without positive nodes.

In both groups, 57% of patients had received neoadjuvant chemotherapy, the majority being cisplatin-based therapy. The median number of lymph nodes that pathologists identified was 39 in the extended lymphadenectomy group and 24 in the standard lymphadenectomy group. The median number of positive nodes was 2 and 1, respectively.

Overall, 13% of patients in the extended lymphadenectomy group and 9% of the standard lymphadenectomy group had local recurrence. First site of recurrence was local for 35% of patients in the extended lymphadenectomy group and 23% of the standard lymphadenectomy group, and distant in 51% and 62%, respectively.

Grade 3 to 5 adverse events (AEs) were found in 157 of 292 patients (54%) in the extended lymphadenectomy group and 132 of 300 (44%) in the standard lymphadenectomy group. The most common grade 3 or higher AEs were as follows: anemia leading to blood transfusion, urinary tract infection, sepsis, wound complications, ileus events, and venous thromboembolic events.

Death happened within 30 days of surgery for 8 patients (3%) in the extended lymphadenectomy group and 1 (1%) in the standard lymphadenectomy group. Within 90 days, deaths occurred in 19 patients (7%) and 7 (2%), respectively. Within 90 days, 7 deaths were reported due to disease progression, although the majority were a result of postoperative complications.

A total of 55% (160 of 292) of patients in the extended lymphadenectomy group and 44% (132 of 300) in the standard lymphadenectomy group had AEs of grade 3 or higher within 90 days after surgery.

Reference

Lerner SP, Tangen C, Svatek RS, et al. Standard or extended lymphadenectomy for muscle-invasive bladder cancer. N Engl J Med. 2024;391(13):1206-1216. doi:10.1056/NEJMoa2401497