Standard Versus Extended Pelvic Lymph Node Dissection in Radical Cystectomy for Bladder Cancer

Muscle invasive bladder cancer (MIBC) comprises, at minimum, an estimated 25-30% of all new cases of bladder cancer in the United States.¹ The American Cancer Society estimates that more than 82,000 new cases of bladder cancer were diagnosed in 2023.² Surgery, particularly radical cystectomy with urinary diversion, remains a gold standard of cure for patients with MIBC. A critical component of this procedure is performing a meticulous pelvic lymph node dissection (PLND), in which pelvic lymph nodes that are harboring potential cancer cells from the urinary bladder are resected and removed along with the bladder. This approach is especially critical since up to 25% of patients undergoing cystectomy may have lymph node-positive disease at the time of cystectomy.³

The goal of PLND during radical cystectomy is to allow for accurate disease staging and potentially prevent the spread of cancer. Traditional standard PLND entails the removal of lymphatic tissue over the external iliac, obturator, and internal iliac regions.⁴ Definitions of extended PLND vary, but it involves removing the presacral, common iliac, and paracaval and interaortocaval packets to the level of the inferior mesenteric artery.⁴ Accurate lymph node staging has clinical implications, as most guidelines recommend administering adjuvant therapy for patients with lymph node-positive disease.

Two major reasons persist as to why urologic surgeons are apprehensive to perform extended PLND on all patients with bladder cancer. First, compared with a traditional standard PLND, an extended PLND adds additional operative time to an already complex and lengthy operation. Second, the risk of complications such as inadvertent injury to the ureter, vessels, and lymphocele formation may be higher with extended PLND. Furthermore, large-scale clinical trials have not demonstrated oncologic survival benefits compared to standard PLND.⁴

The European Association of Urology (EAU) guidelines comment on the value of lymphadenectomy. Specifically, they cite that when comparing data between not performing PLND and performing PLND, most retrospective series they analyzed demonstrated the oncologic therapeutic benefit of PLND.⁵ In addition, the LEA trial, published in 2018 and cited by the EAU guidelines, was the first prospective randomized controlled trial comparing extended PLND to standard (limited) PLND. In this trial, authors conducted a prospective phase 3 study comparing patients undergoing radical cystectomy who were randomized to either standard PLND or extended PLND with a primary outcome of recurrence-free survival (RFS).⁴ Secondary outcomes included overall survival (OS) and patient complications. Among the 401 randomized patients, no benefit was demonstrated for extended PLND compared to standard PLND. Furthermore, the authors noted that lymphoceles were more prevalent in the extended PLND cohort.⁴

The American Urological Association (AUA) also issued guidelines for managing MIBC including recommendations regarding pelvic lymphadenectomy. Similar to the EAU guidelines, the AUA recommends a standard template PLND at minimum for patients undergoing radical cystectomy.⁶ The AUA guidelines also specify that surgeons should aim to obtain at least 12 lymph nodes for a proper lymph node packet evaluation.⁶

Ongoing research efforts continue to identify the optimal patient selection criteria for which patients may optimally benefit from lymphadenectomy while minimizing surgical morbidity. Several trials have recently been published that further highlight the role and extent of pelvic lymph node dissection. SWOG 1011 was a phase 3, randomized, clinical trial presented at the 2023 ASCO® Annual Meeting. In this trial, presented by Dr. Seth Lerner, the authors sought to compare extended PLND to standard PLND in patients with cT2-4a N0-2 MIBC.⁷ Thirty-six surgeons across 27 sites enrolled 592 patients and randomized them into extended and standard cohorts. The authors demonstrated no evidence in the rate of nodal metastasis between the 2 cohorts (26% vs 24%), and the use of extended PLND was associated with twice the rate of grade 3-4 adverse events (16% vs 8%).⁷ No difference in disease-free survival was observed between the 2 arms at a median follow-up of 6.1 years.⁷

Although these randomized trials have demonstrated no benefit, some larger, retrospective meta-analyses have suggested there may be some therapeutic benefit for extended PLND. Wang et al performed a meta-analysis of 10 studies comparing nearly 4000 patients undergoing either extended PLND or nonextended PLND and demonstrated that extended PLND was associated with an improved RFS; however, the authors failed to demonstrate any benefit for extended PLND in relationship to improved OS.⁸

In conclusion, a combination of current guideline recommendations and the latest randomized clinical trials give surgeons clarity regarding the benefit of performing extended PLND in bladder cancer. Despite higher nodal yields in extended PLND, the concerns regarding surgical morbidity without definitive therapeutic benefit make extended PLND an area of continued research and debate in urologic oncology. Ultimately, the decision to perform an extended lymphadenectomy should be made on a patient-by-patient basis while carefully considering the potential benefits and risks.

Akhil Abraham Saji, MD, Fellow at the University of Southern California, is a urologist specializing in minimally invasive surgery and urologic oncology with an interest in technology-driven innovation within health care.

References:

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7. Lerner SP, Tangen C, Svatek RS, et al. SWOG S1011: a phase III surgical trial to evaluate the benefit of a standard versus an extended lymphadenectomy performed at time of radical cystectomy for muscle invasive urothelial cancer. J Clin Oncol. 2023. doi:10.1200/JCO.2023.41.16_suppl.4508
8. Wang Y-C, Wu J, Dai B, et al. Extended versus non-extended lymphadenectomy during radical cystectomy for patients with bladder cancer: a meta-analysis of the effect on long-term and short-term outcomes. World J Surg Oncol. 2019;17(1):225. doi:10.1186/s12957-019-1759-5