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Role of Lymphadenectomy During Radical Cystectomy for Non-muscle Invasive Bladder Cancer: Results From a Multi-Institutional Experience

  • Abhinav Khanna 1,
  • Tanner Miest 2,
  • Vidit Sharma 1,
  • Rebecca Campbell 3,
  • Patrick Hensley 2,
  • Prabin Thapa 1,
  • Andrew Zganjar 1,
  • Matthew K Tollefson 1,
  • R Houston Thompson 1,
  • Igor Frank 1,
  • R J Karnes 1,
  • Prithvi B Murthy 3,
  • Georges P Haber 3,
  • Neema Navai 2,
  • Ashish M Kamat 2,
  • Colin Dinney 2,
  • Byron Lee 3,
  • Stephen A Boorjian 1
1 Department of Urology, Mayo Clinic, Rochester, Minnesota, USA 2 Department of Urology, Maryland Anderson Cancer Center, Houston, Texas, USA 3 Glickman Urologic and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA

Publication: Journal of Urology, October 2021


While lymph node dissection (LND) at radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) has been studied extensively, the role of LND for non-muscle invasive bladder cancer (NMIBC) remains incompletely defined. Herein, we aim to assess the association between extent of LND during RC for NMIBC and local pelvic recurrence-free survival (LPRS), cancer-specific survival (CSS), and overall survival (OS).


A multi-institutional retrospective review was performed of patients with NMIBC undergoing RC at three large tertiary referral centers. To identify a threshold for lymph node yield (LNY) to optimize LPRS, CSS, and OS, separate Cox regression models were developed for each possible LNY threshold. Model performance including Q-statistics and hazard ratios (HR) were used to identify optimal LNY thresholds.


A total of 1647 patients underwent RC for NMIBC, with a median LNY of 15 (quartiles 9,23). Model performance curves suggested LNY of 10 and 20 to optimize LPRS and CSS/OS, respectively. On multivariable regression, LNY>10 was associated with lower risk of LPR compared to LNY≤10 (HR 0.63, 95% CI 0.42-0.93, p=0.02). Similarly, LNY>20 was associated with improved CSS (HR 0.67,95% CI 0.52–0.87, p=0.002) and OS (HR 0.75,95% CI 0.64–0.88, p <0.001) compared to LNY≤20. Similar results were observed in the cT1 and cTis subgroups.


Greater extent of LND during RC for NMIBC is associated with improved LPRS, CSS, and OS, supporting the inclusion of LND during RC for NMIBC, particularly among patients with cTis or cT1 disease. Future prospective studies are warranted to assess the ideal anatomic template of LND in NMIBC.

Expert's summary

By Prof. Evanguelos Xylinas

Radical cystectomy with concomitant bilateral lymph node dissection (LND) is the standard of care surgical management of muscle-invasive bladder cancer. This therapeutic strategy is supported by retrospective evidence of the oncological benefit associated with lymph node dissection and is under investigation in two randomised clinical trials, which aim to determine the ideal anatomical template. In contrast, the current evidence supporting the role of LND for non-muscle invasive bladder cancer treated with radical cystectomy is limited, despite rates of pN+ disease ranging from 8 to 16%, therefore highlighting the added benefit of lymph node dissection in this setting in terms of staging and prognostication.

Khanna et al. aimed to assess the oncological benefit associated with the lymph node dissection performance in non-muscle invasive bladder cancer patients by performing a retrospective multicentre study at three large tertiary referral centres in the United States.

Overall, the study included 1647 patients between 1980 and 2018 (307cTa, 306 cTis, and 974 cT1). Of note, only 64 (3.9%) patients did not undergo any lymph node dissection, and the median number of lymph nodes examined was 15 (quartiles 9-23), both demonstrating the selection of the centres included in the study. After a median follow-up of 4.1 years, 313 patients experienced a recurrence of urothelial carcinoma, including 102 with a local pelvic recurrence. 864 patients died, of which 341 from the disease. The authors demonstrated an association between the extent of lymph node dissection and oncologic outcomes. Patients with a lymph node yield >10 nodes had a significantly higher 5-year local pelvic recurrence-free survival compared to patients with a lymph node yield ≤10 (93.7% vs 91%;p=0.003). Similarly, patients with a lymph node yield >20 had a significantly higher 5-year CSS (86.7% vs 78.4%;p=0.002) and 5-year OS (75.4% vs 65.3%;p<0.001) than patients with a lymph node yield ≤20.

Expert's comment

The authors have to be congratulated for performing this retrospective but high-quality study asking a really practical question about the performance of lymph node dissection at the time of radical cystectomy for a non-muscle invasive disease and, if this performance is sufficient, the question of the extent of it. The authors demonstrated that an extended dissection, in terms of the number of lymph nodes examined, positively impacted the oncological outcomes of the patients. This is in line with previous population-based studies, which have shown an impact of lymph node dissection in non-muscle-invasive bladder cancer patients in terms of overall survival, thereby enhancing our knowledge of the impact of lymph node dissection on disease recurrence/occurrence and cancer-specific mortality.

The results of the study by Khanna et al. also question the results of the German randomised clinical trial of extended-versus-limited lymph node dissection, which did not demonstrate a superiority of extended LND in a population of muscle-invasive bladder cancer patients but did include 13.7% of cT1 disease patients. Interestingly, the uro-oncological community partly attributes the negative results of this trial to the inclusion of cT1 NMIBC patients. The study by Khanna et al. currently challenges this interpretation by demonstrating an added value of lymph node dissection in non-muscle-invasive bladder cancer patients. Unfortunately, the awaited results of the SWOG 1011 trial, which compared standard and extended lymph node dissection in 658 patients, will not help answer that question as it included cT2-T4a patients only.