(UroToday.com) The 2024 American Urological Association (AUA) annual meeting featured a plenary session, and a presentation by Dr. Seth Lerner discussing subgroup analysis results from SWOG S1011, assessing standard versus an extended lymphadenectomy at the time of radical cystectomy for muscle-invasive bladder cancer (MIBC).
The primary objective of SWOG S1011 was to compare disease-free survival in patients undergoing radical cystectomy for muscle-invasive bladder cancer treated with radical cystectomy and extended pelvic lymph node dissection versus standard pelvic lymph node dissection. Secondary objectives included: overall survival, operative time, post-operative morbidity (from surgery until 90 days after surgery), length of hospital stay, lymph node counts and lymph node density, as well as adjuvant chemotherapy received. The study design for SWOG S1011 is as follows:
Statistically, assuming a 3-year disease-free survival in the standard lymph node group (based on a review of 8 surgical series 2000-2009, including 7,957 patients), there would be 85% power to detect a 10-12% improvement in 3-year disease-free survival with extended lymph node dissection (HR 0.72), with a sample size of 564 eligible patients (282 per arm). Assuming a 10% intraoperative ineligibility, the total target accrual was ~620 patients. Ultimately, 592 patients were randomized (n = 300 standard lymph node dissection vs n = 292 extended lymph node dissection), with well-balanced clinical stage and neoadjuvant chemotherapy (57% receiving cisplatin-based chemotherapy) variables between the two groups:
Patients undergoing extended lymph node dissection had a median of 39 nodes removed (range: 15-94) compared to 24 (range: 6-61) for standard lymph node dissection. Furthermore, there was little difference in median number of positive nodes (2, range 1-16 vs 1, range 1-35), between patients receiving extended versus standard lymph node dissection. Additional key findings included a longer median operative time (5.9 hours, IQR 5.1-7.0 vs 5.3 hours, IQR 4.5-6.6; p = 0.001) and more estimated blood loss (700 cc, IQR 500-1000 vs 600 cc, IQR 400-900; p = 0.024) for the extended lymph node dissection group:
Importantly, 30-day mortality rate was 30% in the standard lymph node dissection group versus 2.7% in the extended lymph node dissection group, with corresponding 90-day mortality rates of 2.4% vs 6.5%. Higher VTE rates were also noted in the extended lymph node dissection arm:
Adjusting for treatment arm and stratification factors, there was no difference in disease-free or overall survival among patients with variant histology, however, there was for ileal conduit versus neobladder:
In patients that received prior neoadjuvant chemotherapy versus those that did not, receipt of neoadjuvant chemotherapy was associated with improved disease-free survival (HR 0.63, 95% CI 0.49-0.81):
Dr. Lerner provided the following thoughts as to why there is no added benefit to extended lymph node dissection:
- The assumption of a 3-year 55% disease-free survival in the control arm, wherein reality the true 3-year disease-free survival was 62%
- The assumption of a 5-year 55% overall survival in the control arm, wherein reality the true 5-year overall survival was 63%
- Completeness of the standard lymph node dissection was quite thorough at 24 nodes, which had a very similar range in the number of positive nodes in both arms
- Disease-free survival and overall survival from retrospective data are from the pre-neoadjuvant chemotherapy era, given that 57% of patients had neoadjuvant chemotherapy in this trial, and the prognosis is better in the current era
Dr. Lerner concluded his presentation discussing subgroup analysis results from SWOG S1011, assessing standard versus an extended lymphadenectomy at the time of radical cystectomy for muscle-invasive bladder cancer with the following take-home messages:
- Patients undergoing radical cystectomy and extended lymph node dissection had increased node yield, but similar pathologic T stage and rate of node metastasis
- There was no indication of disease-free survival or overall survival benefit for extended lymph node dissection compared to standard lymph node dissection, although salvage lymph node dissection was associated with higher pelvic recurrence in N+ patients
- Extended lymph node dissection was also associated with greater morbidity and higher peri-operative mortality: longer OR time, blood loss, higher number of progression events within 90 days, and higher VTE rate
Presented by: Seth Lerner, MD, FACS, Professor of Urology, Baylor College of Medicine, Houston, TX
Written by: Zachary Klaassen, MD, MSc - Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Urological Association (AUA) Annual Meeting, San Antonio, TX, Fri, May 3 - Mon, May 6, 2024.