Abstract
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.
Key points
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Pelvic lymph node dissection (PLND) during radical cystectomy for bladder cancer seems to provide oncological benefit.
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PLND also provides useful prognostic information, such as tumour burden, lymph node density, and extracapsular extension of metastatic lymph nodes, which can guide management.
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Extended PLND templates seem to provide optimal recurrence-free and cancer-specific survival, whereas the use of super-extended PLND provides no added benefit.
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Increased nodal yield improves oncological outcomes in patients with node-negative or node-positive disease.
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Despite the current evidence, recommendations for optimal PLND techniques during radical cystectomy for muscle-invasive bladder cancer are limited.
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References
Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin. https://doi.org/10.3322/caac.21442 (2018).
Witjes, J. A. et al. EAU guidelines on muscle-invasive and metastatic bladder cancer. European Association of Urology https://uroweb.org/wp-content/uploads/EAU-Guidelines-Muscle-invasive-and-Metastatic-Bladder-Cancer-Guidelines-2016.pdf (2016).
Australian Institute of Health Welfare. Cancer survival and prevalence in Australia: period estimates from 1982 to 2010. Asia Pac. J. Clin. Oncol. 9, 29–39 (2013).
Ku, J. H. et al. Lymph node density as a prognostic variable in node-positive bladder cancer: a meta-analysis. BMC Cancer 15, 447–457 (2015).
Kassouf, W. et al. Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder. Urol. Oncol. 31, 480–486 (2013).
Vieweg, J., Gschwend, J. E., Herr, H. W. & Fair, W. R. The impact of primary stage on survival in patients with lymph node positive bladder cancer. J. Urol. 161, 72–76 (1999).
Bruins, H. M. et al. Clinical outcomes and recurrence predictors of lymph node positive urothelial cancer after cystectomy. J. Urol. 182, 2182–2187 (2009).
Herr, H. W. Superiority of ratio based lymph node staging for bladder cancer. J. Urol. 169, 943–945 (2003).
Karl, A. et al. The impact of lymphadenectomy and lymph node metastasis on the outcomes of radical cystectomy for bladder cancer. Eur. Urol. 55, 826–835 (2009).
Konety, B. R., Joslyn, S. A. & O’Donnell, M. A. Extent of pelvic lymphadenectomy and its impact on outcome in patients diagnosed with bladder cancer: analysis of data from the Surveillance, Epidemiology and End Results Program data base. J. Urol. 169, 946–950 (2003).
Stein, J. P., Cai, J., Groshen, S. & Skinner, D. G. Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: concept of lymph node density. J. Urol. 170, 35–41 (2003).
Crozier, J., Papa, N., Sengupta, S., Bolton, D. M. & Lawrentschuk, N. Changing practice of pelvic lymph node dissection in management of primary bladder cancer. Minerva Urol. Nefrol 68, 106–111 (2015).
Leissner, J. et al. Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study. J. Urol. 171, 139–144 (2004).
Bi, L. et al. Extended versus non-extended pelvic lymph node dissection and their influence on recurrence-free survival in patients undergoing radical cystectomy for bladder cancer: a systematic review and meta-analysis of comparative studies. BJU Int. 113, E39–E48 (2014).
Jensen, J. B., Ulhoi, B. P. & Jensen, K. M. Extended versus limited lymph node dissection in radical cystectomy: impact on recurrence pattern and survival. Int. J. Urol. 19, 39–47 (2012).
Herr, H., Lee, C., Chang, S. & Lerner, S. Bladder Cancer Collaborative Group. Standardization of radical cystectomy and pelvic lymph node dissection for bladder cancer: a collaborative group report. J. Urol. 171, 1823–1828 (2004).
Weisbach, L. et al. Lymph node dissection during radical cystectomy for bladder cancer treatment: considerations on relevance and extent. Int. Urol. Nephrol. 45, 1561–1567 (2013).
Dorin, R. P. et al. Lymph node dissection technique is more important than lymph node count in identifying nodal metastases in radical cystectomy patients: a comparative mapping study. Eur. Urol. 60, 946–952 (2011).
Kitamura, H. Editorial comment to stage-specific impact of extended versus standard pelvic lymph node dissection in radical cystectomy. Int. J. Urol. 20, 398 (2013).
Abol-Enein, H., El-Baz, M., Abd El-Hameed, M. A., Abdel-Latif, M. & Ghoneim, M. A. Lymph node involvement in patients with bladder cancer treated with radical cystectomy: a patho-anatomical study — a single center experience. J. Urol. 172, 1818–1821 (2004).
Roth, B. et al. A new multimodality technique accurately maps the primary lymphatic landing sites of the bladder. Eur. Urol. 57, 205–211 (2010).
Roth, B. et al. Is bilateral extended pelvic lymphadenectomy necessary for strictly unilateral invasive bladder cancer? J. Urol. 187, 1577–1582 (2012).
Roth, B. et al. Does the lymphatic drainage pattern of the lateral bladder wall make a bilateral pelvic lymphadenectomy (PLND) unnecessary in strictly laterally localized invasive bladder cancer? Results of a multimodality mapping study. J. Urol. 185, e562 (2011).
Vazina, A. et al. Stage specific lymph node metastasis mapping in radical cystectomy specimens. J. Urol. 171, 1830–1834 (2004).
Park, W. K. & Kim, Y. S. Pattern of lymph node metastasis correlates with tumor location in bladder cancer. Kor. J. Urol. 53, 14–17 (2012).
Seiler, R., Von Gunten, M., Thalmann, G. N. & Fleischmann, A. Pelvic lymph nodes: distribution and nodal tumour burden of urothelial bladder cancer. J. Clin. Pathol. 63, 504–507 (2010).
Mattei, A. et al. The template of the primary lymphatic landing sites of the prostate should be revisited: results of a multimodality mapping study. Eur. Urol. 53, 118–125 (2008).
Simone, G. et al. Stage-specific impact of extended versus standard pelvic lymph node dissection in radical cystectomy. Int. J. Urol. 20, 390–397 (2013).
Larcher, A. et al. Differential effect on survival of pelvic lymph node dissection at radical cystectomy for muscle invasive bladder cancer. Eur. J. Surg. Oncol. 41, 353–360 (2015).
Bruins, H. M. et al. The impact of the extent of lymphadenectomy on oncologic outcomes in patients undergoing radical cystectomy for bladder cancer: a systematic review. Eur. Urol. 66, 1065–1077 (2014).
Brossner, C., Pycha, A., Toth, A., Mian, C. & Kuber, W. Does extended lymphadenectomy increase the morbidity of radical cystectomy? BJU Int. 93, 64–66 (2004).
Morgan, T. M. et al. Lymph node yield at radical cystectomy predicts mortality in node-negative and not node-positive patients. Urology 80, 632–640 (2012).
May, M. et al. Association between the number of dissected lymph nodes during pelvic lymphadenectomy and cancer-specific survival in patients with lymph node-negative urothelial carcinoma of the bladder undergoing radical cystectomy. Ann. Surg. Oncol. 18, 2018–2025 (2011).
Buscarini, M., Josephson, D. Y. & Stein, J. P. Lymphadenectomy in bladder cancer: a review. Urol. Int. 79, 191–199 (2007).
Sharir, S. & Fleshner, N. E. Lymph node assessment and lymphadenectomy in bladder cancer. J. Surg. Oncol. 99, 225–231 (2009).
Dhar, N. B. et al. Outcome after radical cystectomy with limited or extended pelvic lymph node dissection. J. Urol. 179, 873–878; discussion 878 (2008).
Holmer, M. et al. Extended lymph node dissection in patients with urothelial cell carcinoma of the bladder: can it make a difference? World J. Urol. 27, 521–526 (2009).
Poulsen, A. L., Horn, T. & Steven, K. Radical cystectomy: extending the limits of pelvic lymph node dissection improves survival for patients with bladder cancer confined to the bladder wall. J. Urol. 160, 2015–2019 (1998).
Stein, J. P. Lymphadenectomy in bladder cancer: how high is “high enough”? Urol. Oncol. 24, 349–355 (2006).
Zehnder, P. et al. Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study. J. Urol. 186, 1261–1268 (2011).
Moller, M. K., Hoyer, S. & Jensen, J. B. Extended versus superextended lymph-node dissection in radical cystectomy: subgroup analysis of possible recurrence-free survival benefit. Scand. J. Urol. 50, 175–180 (2016).
Roth, B. & Burkhard, F. C. The role of lymphadenectomy in radical cystectomy. Eur. Urol. Supplements 9, 19–24 (2010).
Youssef, R. F. & Raj, G. V. Lymphadenectomy in management of invasive bladder cancer. Int. J. Surg. Oncol. 2011, 758189 (2011).
Hermans, T. J. et al. Variations in pelvic lymph node dissection in invasive bladder cancer: a Dutch nationwide population-based study during centralization of care. Urol Oncol. 34, 532.e7–532.e12 (2016).
Zaffuto, E. et al. Contemporary rates of adherence to international guidelines for pelvic lymph node dissection in radical cystectomy: a population-based study. World J. Urol. https://doi.org/10.1007/s00345-018-2306-7 (2018).
Leissner, J., Hohenfellner, R., Thuroff, J. W. & Wolf, H. K. Lymphadenectomy in patients with transitional cell carcinoma of the urinary bladder; significance for staging and prognosis. BJU Int. 85, 817–823 (2000).
Wright, J. L., Lin, D. W. & Porter, M. P. The association between extent of lymphadenectomy and survival among patients with lymph node metastases undergoing radical cystectomy. Cancer 112, 2401–2408 (2008).
Kurtz, G. A., McKinney, J. L., Law, C. H., Jewett, M. A. & Sharir, S. Toward quality measures in bladder cancer surgery: a population-based assessment of radical cystectomy in Ontario. J. Urol. 179, 581 (2008).
Koppie, T. M., Vickers, A. J., Vora, K., Dalbagni, G. & Bochner, B. H. Standardization of pelvic lymphadenectomy performed at radical cystectomy: can we establish a minimum number of lymph nodes that should be removed? Cancer 107, 2368–2374 (2006).
Abdel-Latif, M., Abol-Enein, H., El-Baz, M. & Ghoneim, M. A. Nodal involvement in bladder cancer cases treated with radical cystectomy: incidence and prognosis. J. Urol. 172, 85–89 (2004).
Herr, H. W. et al. Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. J. Urol. 167, 1295–1298 (2002).
Lerner, S. P. et al. The rationale for en bloc pelvic lymph node dissection for bladder cancer patients with nodal metastases: long-term results. J. Urol. 149, 758–755 (1993).
Fleischmann, A., Thalmann, G. N., Markwalder, R. & Studer, U. E. Extracapsular extension of pelvic lymph node metastases from urothelial carcinoma of the bladder is an independent prognostic factor. J. Clin. Oncol. 23, 2358–2365 (2005).
Kassouf, W. et al. Evaluation of the relevance of lymph node density in a contemporary series of patients undergoing radical cystectomy. J. Urol. 176, 53–57 (2006).
Kassouf, W. et al. Lymph node density is superior to TNM nodal status in predicting disease-specific survival after radical cystectomy for bladder cancer: analysis of pooled data from MDACC and MSKCC. J. Clin. Onc. 26, 121–126 (2008).
Ahn, T. S. et al. Extracapsular extension of pelvic lymph node metastasis is an independent prognostic factor in bladder cancer: a systematic review and meta-analysis. Ann. Surg. Oncol. 22, 3745–3750 (2015).
Shao, P. et al. Laparoscopic extended pelvic lymph node dissection during radical cystectomy: technique and clinical outcomes. BJU Int. 108, 124–128 (2011).
Yuan, J. B. et al. Laparoscopic pelvic lymph node dissection system based on preoperative primary tumour stage (T stage) by computed tomography in urothelial bladder cancer: results of a single-institution prospective study. BJU Int. 112, E87–E91 (2013).
US National Library of Medicine. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01224665 (2018).
US National Library of Medicine. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01215071 (2016).
Froehner, M. et al. Relationship of the number of removed lymph nodes to bladder cancer and competing mortality after radical cystectomy. Eur. Urol. 66, 987–990 (2014).
Clark, P. et al. Bladder Cancer. NCCN Clinical Practice Guidelines in Oncology. J. Natl Compr. Canc Netw. 14, 1213–1224 (2016).
Lobo, N. et al. Landmarks in the treatment of muscle-invasive bladder cancer. Nat. Rev. Urol. 14, 565–574 (2017).
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S.M. and J.C. researched data for the article; M.P. and D.B. made substantial contributions to discussions of content; M.P., S.M., S.S., and J.C. wrote the article; and M.P., S.S., D.B., and N.L. reviewed and edited the manuscript before submission.
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Perera, M., McGrath, S., Sengupta, S. et al. Pelvic lymph node dissection during radical cystectomy for muscle-invasive bladder cancer. Nat Rev Urol 15, 686–692 (2018). https://doi.org/10.1038/s41585-018-0066-1
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DOI: https://doi.org/10.1038/s41585-018-0066-1
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