Update of the Diagnostic and Therapeutic Role of the Pelvic Lymph Node Dissection Boundaries During Radical Cystectomy in Muscle Invasive Bladder Cancer

Standard Lymph Node Dissection for Bladder Cancer: Significant Variability in the Number of Reported Lymph Nodes

Radical Cystectomy and Extended Pelvic Lymphadenectomy: Survival of Patients With Lymph Node Metastasis Above the Bifurcation of the Common Iliac Vessels Treated With Surgery Only

Outcome After Radical Cystectomy With Limited or Extended Pelvic Lymph Node Dissection

Super Extended Versus Extended Pelvic Lymph Node Dissection in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Comparative Study

Radical cystectomy is the gold-standard treatment option for muscle-invasive and metastatic bladder cancer. At the time of cystectomy, up to 25% of patients harbour metastatic lymph node deposits. These deposits most frequently occur in the obturator fossa, but can be as proximal as the interaortocaval region. Thus, the use of concurrent pelvic lymph node dissection (PLND) with cystectomy has been increasingly reported. Data from studies including many patients suggest substantial oncological benefit in PLND cohorts versus non-PLND cohorts, irrespective of pathological nodal status. Additionally, PLND provides useful prognostic information, including disease burden, lymph node density, and extracapsular extension of metastatic lymph nodes. Accordingly, the National Comprehensive Cancer Network guidelines advocate the use of PLND during radical cystectomy for muscle-invasive bladder cancer. Despite this recommendation, a lack of consensus exists regarding the optimal PLND template. Comparative series suggest that extended PLND provides improved recurrence-free survival and cancer-specific survival compared with more limited PLND templates. More extensive templates (such as super-extended PLND) provide no additional survival benefit at the potential cost of increased operative time and patient morbidity. In addition to extended PLND templates, increased nodal harvest confers an oncological benefit in patients with node-positive disease or in patients with node-negative disease. Accordingly, recommendations for a minimum nodal yield have been proposed. Despite the growing body of evidence, formal recommendations by oncological and urological authoritative bodies have been limited owing to the lack of randomized data and level I evidence.

BackgroundPatients diagnosed with non-muscle-invasive bladder cancer (NMIBC) who are at a very high risk of disease progression and failure of Bacillus Calmette-Guerin treatment are recommended to undergo immediate radical cystectomy (RC). The role and optimal degree of pelvic lymph node dissection (PLND) during RC for NMIBC patients, however, have not been well investigated.Patients and methodsThe Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients. Overall survival (OS) was assessed with the Kaplan–Meier technique. Multivariable Cox regression analysis was conducted to determine independent factors of OS.ResultsA total of 1,701 patients were identified in the SEER database from 2004 to 2015. Any level of PLND (>0 lymph nodes examined) was performed in 1,092 patients (64.2%). The median number of lymph nodes examined was 8 (interquartile range, 0–20) in T1, 0 (interquartile range, 0–11) in Ta, and 0 (interquartile range, 0–14) in Tia patients. Compared with non-PLND, any level of PLND improved OS in T1 but not in Ta or Tis patients. Compared to limited (1–9 lymph nodes examined) and non-PLND, extensive PLND (lymph nodes examined ≥10) resulted in better OS only in T1 patients (all p < 0.001, adjusted significance level = 0.017). PLND was identified as a independent protective factor for OS.ConclusionBased on the SEER database, we found that PLND during RC led to better OS and extensive PLND was associated with better OS in T1 but not in Ta or Tis patients. The implementation of PLND was insufficient both in population proportions and scope.

Although radical cystectomy with pelvic lymph node dissection (PLND) is the standard treatment for muscle-invasive bladder cancer, the optimal extent of PLND and the minimum number of nodes that should be examined for pathology remain unclear. However, evidence is growing that extended PLND has additional diagnostic and therapeutic benefits relative to standard PLND. In particular, a more meticulous and extended PLND may improve the disease-free survival of node-negative patients because it removes undetected micrometastases. Indeed, some patients with positive nodes can be cured by surgery alone, even those with gross adenopathy. Increasing lines of evidence also suggest that the extent of the primary bladder tumor, the number of lymph nodes that are removed, and the lymph node tumor burden are important prognostic variables in patients undergoing cystectomy. Therefore, extended PLND may not only provide improved prognostic information, it may also have a clinically significant therapeutic benefit for both lymph node-positive and node-negative patients undergoing radical cystectomy. Although the absolute limits of PLND remain to be determined, evidence supports the notion that a more extended PLND should include the common iliac vessels and presacral lymph nodes at cystectomy. Such PLND should only be performed in patients who are appropriate surgical candidates. Prospective, randomized trials are needed to properly establish the extent of PLND that is required to generate these benefits.

e16609 Background: Pelvic lymph node dissection (PLND) has been a critical component of radical cystectomy in patients with bladder cancer. Radical surgery with standard PLND improves survival in high-risk non-muscle-invasive and muscle-invasive cases. However, the role of extended PLND in these settings is unclear. Methods: A comprehensive literature search of major bibliographic databases was performed from inception to November 2024. Studies comparing extended or super-extended PLND with standard PLND were identified. Data for clinical outcomes were extracted and pooled estimates were calculated using a random effects model with RevMan 5.4. Results: 11 studies (2 RCTs and 9 observational) were included reporting data for 4,001 patients (standard; 1997, extended/super extended; 2204) who underwent radical cystectomy. The pooled analysis demonstrated that extended PLND was associated with significantly better recurrence-free survival (RFS) (HR = 0.67, 95% CI: 0.60-0.74). Standard PLND led to significantly higher 5-year recurrence rates (RR = 1.44, 95% CI: 1.28-1.62) compared to the extended approach. The pooled estimates for disease-specific survival (HR = 0.86, 95% CI: 0.62-1.19), overall survival (OS) (HR = 0.99, 95% CI: 0.86-1.16), and complications remained comparable. Conclusions: Extended PLND improves recurrence-free survival and lowers recurrence rates compared to standard PLND. However, the current evidence is mainly based on retrospective studies, and additional RCTs are warranted to further delineate the role of extended PLND. Clinical outcomes and pooled estimates. Clinical Outcome HR/RR (95% CI) p-value I2 (%) Disease-specific survival 0.86 (0.62-1.19) 0.36 73 RFS 0.67 (0.60-0.74) &lt;0.00001 18 OS 0.99 (0.86-1.16) 0.94 0 5-year recurrence rates 1.44 (1.28-1.62) &lt;0.00001 0 Early Clavien-Dindo Grade 3-4 complications (30 days) 0.90 (0.63-1.29) 0.57 62 Late Clavien-Dindo Grade 5 complications (90 days) 0.90 (0.77-1.04) 0.14 0 Early mortality (30 days) 0.88 (0.39-1.96) 0.75 0 Late mortality (90 days) 0.98 (0.41-2.37) 0.97 0

To evaluate the perioperative, pathological, and oncological outcomes from surgeon-led pathological staging of pelvic lymph node (LN) metastases at the time of robot-assisted radical prostatectomy (RARP). Over the 6-year period of 2006-2012, three distinct pelvic LN dissection (PLND) strategies were used in chronological order at a single cancer referral hospital. Strategies were characterised by both an omission of PLND (pNx) vs inclusion decision threshold, and standard vs extended templates for patients selected for PLND. The three cohorts included: (i) omission vs standard template (04/2006-10/2007), for dominant Gleason score 4-5 or a prostate-specific antigen (PSA) level of >10 ng/mL; (ii) omission/standard vs extended template (11/2007-12/2010), for dominant Gleason score 4-5, PSA level of >10 ng/mL, any single core >7 mm, or >3 ipsilateral positive cores; and (iii) extended template with minimal exceptions (01/2011-08/2012). Standard outcomes data compared included: Clavien-Dindo complication rates, LN metrics (yield, percentage positive), and biochemical recurrence (BCR). A novel metric comprised 'pNx regret': the rate of pNx patients upgraded/upstaged. Exploratory analyses included selection criteria for reduced PLND templates, i.e. low-yield subsets. Standard PLND yielded 8-10 LNs and a positive-LN yield of 2.2-6.2%. The addition of an extended PLND (E-PLND) significantly increased the yield to 14-20 LNs and the positive-LN yield to 17.4-18.4% (both P < 0.001). E-PLND had the highest impact on the percentage of positive LNs (%pN1) for high-risk disease (9.3 vs 32.8%, P = 0.002), modest for intermediate risk (4.2 vs 10.9%, P = 0.003), and minimal impact on low risk disease (4.1 vs 0%, P = 0.401). The combined strategies of setting a very low threshold for E-PLND and sending separate LN packets increased the LN yields (18 vs 24, P < 0.001), but did not significantly change the observed %pN1 rates by clinical risk group (P = 0.975). Efforts to reduce the need for E-PLND included omission by clinical criteria, but resulting in 'pNx regret' in 16-19%. A third of patients with unilateral disease and positive LNs were found to have contralateral disease. A subset of men with minimal biopsy volume Gleason score 4 + 3 had pN1 rates after E-PLND of three of 14 (21%) compared to minimal biopsy volume Gleason score 3 + 4 pN1 rates after E-PLND of 0 of 31. E-PLND takes about twice as long to perform but with no statistically significant difference in complications (5.0 vs 6.0%, P = 0.511). The 5-year BCR rates were higher for E-PLND, given the selection criteria, but not different for overall survival. The net benefit of E-PLND remains uncertain, and therapeutic impact will probably require a randomised trial, given the strong selection criteria. E-PLND contributes to oncological staging in a significant number of high- and intermediate-risk patients, and should be bilateral. Immediate concerns include longer operative times, but no higher complication rates.

To perform a narrative review of the contemporary literature on the diagnosis, prognosis and adjuvant management of muscle-invasive bladder cancer (MIBC) patients with pathological pelvic lymph node involvement (pN+) at radical cystectomy. A narrative review of the contemporary literature available on Medline was conducted to report studies evaluating the diagnosis, prognosis and/or adjuvant treatments for MIBC patients with pN+ disease at radical cystectomy. Open or robotic extended pelvic lymph node dissection up to the crossing of the ureter with common iliac vessels can enhance the diagnosis of pN+ MIBC, especially using separate packages for the submission of a maximum number of lymph nodes. The main prognosis factors for pN+ patients are the number of positive and retrieved lymph nodes, lymph node density, extranodal extension as well as lymph node metastasis diameter. Adjuvant chemotherapy is likely to prolong overall survival in pN+ patients treated with radical cystectomy alone while adjuvant immunotherapy using nivolumab has been shown to decrease the risk of recurrence in all pN+ patients, especially those with ypN+ disease after neoadjuvant chemotherapy followed by radical cystectomy. However, few data are currently available on the role of adjuvant radiation therapy, which remains currently experimental for these patients. Multiple parameters have been reported to impact the diagnosis and prognosis of patients with pN+ MIBC at radical cystectomy. Adjuvant management is currently based on chemotherapy and immunotherapy with preliminary data on radiation therapy.

Unilateral Pelvic Lymph Node Dissection in Prostate Cancer Patients Diagnosed in the Era of Magnetic Resonance Imaging–targeted Biopsy: A Study That Challenges the Dogma

Purpose: To evaluate whether extended pelvic lymph node dissection (PLND) improves survival outcomes compared with standard PLND in patients with bladder cancer (BCa) undergoing radical cystectomy (RC), and to assess its potential benefits in patients with prior or concurrent radical nephroureterectomy (p/cRNU).Materials and Methods: A multicenter analysis included 2202 patients with BCa undergoing RC with standard or extended PLND at 11 tertiary centers from 2003 to 2023. Following propensity score matching, 659 pairs (n=1,318), including 128 patients with p/cRNU, were analyzed. Recurrence-free survival (RFS) was the primary outcome, while overall survival (OS), cancer-specific survival (CSS), and readmission rates were secondary outcomes. Survival analyses performed using Kaplan-Meier methods and clustered Cox models.Results: Extended PLND yielded significantly more lymph nodes than standard PLND (median: 27.0 vs. 17.0, p&lt;0.001) but did not improve RFS, CSS, or OS in the overall cohort (all p&gt;0.05). Extended PLND increased readmission rates (28.4% vs. 20.2%, p=0.001) and readmission risk (odds ratio, 1.57; 95% confidence interval [CI], 1.15–2.16, p=0.005). However, subgroup analysis revealed extended PLND significantly improved RFS in patients with p/cRNU (hazard ratio, 0.54; 95% CI, 0.38–0.77; p&lt;0.001).Conclusion: Extended PLND does not provide survival benefits for overall patient population and increases readmission risk but significantly improves RFS in patients with p/cRNU. Tailoring PLND extent based on upper tract disease status is recommended.

Radical cystectomy with pelvic lymph node dissection (PLND) is the preferred treatment for invasive bladder cancer. It not only results in the best disease-free term survival rates, but also provides the most accurate disease staging and most effective local symptom control. Recent investigations have demonstrated a clinical benefit to performance of an extended PLND, including all lymphatic tissue to the level of the aortic bifurcation. This review will summarize recent findings regarding the clinical benefits of radical cystectomy with extended lymphadenectomy, and will also examine the latest surgical techniques for optimizing the performance of this technically demanding procedure. Recent studies have demonstrated increased recurrence-free survival and overall survival rates in patients undergoing radical cystectomy with extended PLND, even in cases of pathologically lymph node negative disease. The growing use of minimally invasive techniques has prompted interest in robotic radical cystectomy and extended PLND, and recent reports have demonstrated the feasibility of this technique. The standardization of extended PLND templates has also been a focus of contemporary research. Contemporary research strongly suggests that all patients undergoing radical cystectomy for bladder cancer should undergo concomitant extended PLND. Randomized trials are still needed to confirm the benefits of extended over 'standard' PLND, and to clarify which patients may receive the greatest benefit from this procedure.

Prediction of the Need for an Extended Lymphadenectomy at the Time of Radical Cystectomy in Patients with Bladder Cancer

• To study the surgical techniques and clinical results of laparoscopic extended pelvic lymph node dissection during radical cystectomy. • From July 2007 to October 2009, 43 patients with bladder carcinoma received laparoscopic radical cystectomy with extended pelvic lymphadenectomy and urinary diversion. • Pelvic lymph node dissection (PLND) was first performed within extended template. • The lower part of aorta and vena cava were isolated from the bifurcation of common iliac artery to the level of the inferior mesenteric artery. • The standard template PLND was continued along the external iliac vessels, internal iliac vessels and obturator nerve. The bladder was then removed laparoscopically and urinary diversion was performed. • All procedures were performed successfully and no open conversion occurred. The duration of the procedure for extended PLND was 90-185 min (mean 125 min) and total duration was 280-470 min (mean 329 min). • Intra-operative blood loss was 200-1500 mL (mean 325 mL) and eight cases received transfusion. Pathological study identified transitional cell carcinoma and a negative margin in all cases. A range of 19-53 lymph nodes were dissected in the patients with a mean of 31.3. • In total, 17 positive nodes were confirmed in 11 cases. Postoperative complications included two cases of bowel obstruction, two cases of mild urine leakage and 17 cases of lymphatic leakage. • Laparoscopic radical cystectomy with extended pelvic lymphadenectomy is indicated in selected patients with bladder cancer. • It is safe, minimally invasive and more lymph nodes can be retrieved with a higher success rate by extended pelvic lymphadenectomy.