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  • Review Article
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Management of patients with muscle-invasive bladder cancer with clinical evidence of pelvic lymph node metastases

Nature Reviews Urology (2024)Cite this article

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Abstract

Identification of clinically positive pelvic lymph node metastases (cN+) in patients with muscle-invasive bladder cancer is currently challenging, as the diagnostic accuracy of available imaging modalities is limited. Conventional CT is still considered the gold-standard approach to diagnose lymph node metastases in these patients. The development of innovative diagnostic methods including radiomics, artificial intelligence-based models and molecular biomarkers might offer new perspectives for the diagnosis of cN+ disease. With regard to the treatment of these patients, multimodal strategies are likely to provide the best oncological outcomes, especially using induction chemotherapy followed by radical cystectomy and pelvic lymph node dissection in responders to chemotherapy. Additionally, the use of adjuvant nivolumab has been shown to decrease the risk of recurrence in patients who still harbour ypT2–T4a and/or ypN+ disease after surgery. Alternatively, the use of avelumab maintenance therapy can be offered to patients with unresectable cN+ tumours who have at least stable disease after induction chemotherapy alone. Lastly, patients with cN+ tumours who are not responding to induction chemotherapy are potential candidates for receiving second-line treatment with pembrolizumab.

Key points

  • Muscle-invasive bladder cancer (MIBC) with clinically positive pelvic lymph-nodes (PLNs) is a particular situation at the interface between localized and metastatic disease.

  • The use of conventional CT is currently recommended for the clinical diagnosis of PLN metastases in patients with MIBC.

  • The development of innovative diagnostic methods including radiomics, AI-based models and genetics might offer new perspectives for the diagnosis of PLN-positive MIBC.

  • Multimodal treatment strategies, especially using induction chemotherapy (ICT) followed by radical cystectomy and pelvic lymph node dissection, provide the best oncological outcomes in patients with cN+ cM0 MIBC.

  • Adjuvant immunotherapy can be offered to patients who still harbour PLN metastases at the final pathology analysis after ICT followed by radical cystectomy (restricted to patients harbouring PDL1 expression ≥1% in Europe).

  • Maintenance therapy with avelumab can be offered to patients with unresectable cN+ MIBC — especially patients with cN2–N3 disease — who achieved at least stable disease after ICT alone, whereas non-responders to ICT are potential candidates to receive second-line pembrolizumab.

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Fig. 1: Treatment algorithm for patients with muscle-invasive bladder cancer and clinical evidence of pelvic lymph node metastases.

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References

  1. Witjes, J. A. et al. European Association of Urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2020 guidelines. Eur. Urol. 79, 82–104 (2021).

    Article  CAS  PubMed  Google Scholar 

  2. Mitra, A. P. et al. Management trends and outcomes of patients undergoing radical cystectomy for urothelial carcinoma of the bladder: evolution of the university of Southern California experience over 3,347 cases. J. Urol. 207, 302–313 (2022).

    Article  PubMed  Google Scholar 

  3. Bellmunt, J. & Petrylak, D. P. New therapeutic challenges in advanced bladder cancer. Semin. Oncol. 39, 598–607 (2012).

    Article  CAS  PubMed  Google Scholar 

  4. Stein, J. P. et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J. Clin. Oncol. 19, 666–675 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Hautmann, R. E., de Petriconi, R. C., Pfeiffer, C. & Volkmer, B. G. Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients. Eur. Urol. 61, 1039–1047 (2012).

    Article  PubMed  Google Scholar 

  6. Horn, T. et al. Clinical prognosticators of survival in patients with urothelial carcinoma of the bladder and lymph node metastases after cystectomy with curative intent. World J. Urol. 33, 813–819 (2015).

    Article  PubMed  Google Scholar 

  7. Swinnen, G. et al. FDG-PET/CT for the preoperative lymph node staging of invasive bladder cancer. Eur. Urol. 57, 641–647 (2010).

    Article  PubMed  Google Scholar 

  8. Hugen, C. M., Duddalwar, V. & Daneshmand, S. Preoperative imaging for clinical staging prior to radical cystectomy. Curr. Urol. Rep. 17, 62 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hautmann, R. E., de Petriconi, R. C. & Volkmer, B. G. Lessons learned from 1,000 neobladders: the 90-day complication rate. J. Urol. 184, 990–994 (2010).

    Article  PubMed  Google Scholar 

  10. Paik, M. L., Scolieri, M. J., Brown, S. L., Spirnak, J. P. & Resnick, M. I. Limitations of computerized tomography in staging invasive bladder cancer before radical cystectomy. J. Urol. 163, 1693–1696 (2000).

    Article  CAS  PubMed  Google Scholar 

  11. Drieskens, O. et al. FDG-PET for preoperative staging of bladder cancer. Eur. J. Nucl. Med. Mol. Imaging 32, 1412–1417 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. Tritschler, S. et al. Staging of muscle-invasive bladder cancer: can computerized tomography help us to decide on local treatment? World J. Urol. 30, 827–831 (2012).

    Article  PubMed  Google Scholar 

  13. Frączek, M. et al. Evaluation of lymph node status in patients with urothelial carcinoma — still in search of the perfect imaging modality: a systematic review. Transl. Androl. Urol. 7, 78303–78803 (2018).

    Article  Google Scholar 

  14. Horn, T. et al. Evaluation of computed tomography for lymph node staging in bladder cancer prior to radical cystectomy. Urol. Int. 96, 51–56 (2016).

    Article  CAS  PubMed  Google Scholar 

  15. Dorfman, R. E., Alpern, M. B., Gross, B. H. & Sandler, M. A. Upper abdominal lymph nodes: criteria for normal size determined with CT. Radiology 180, 319–322 (1991).

    Article  CAS  PubMed  Google Scholar 

  16. Li, Y. et al. Computed tomography and magnetic resonance imaging evaluation of pelvic lymph node metastasis in bladder cancer. Chin. J. Cancer 37, 3 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Crozier, J. et al. Comparative sensitivity and specificity of imaging modalities in staging bladder cancer prior to radical cystectomy: a systematic review and meta-analysis. World J. Urol. 37, 667–690 (2019).

    Article  PubMed  Google Scholar 

  18. Schmid, S. C. et al. Prognostic value of computed tomography before radical cystectomy in patients with invasive bladder cancer: imaging predicts survival. World J. Urol. 34, 569–576 (2016).

    Article  PubMed  Google Scholar 

  19. Moschini, M. et al. Clinical lymphadenopathy in urothelial cancer: a transatlantic collaboration on performance of cross-sectional imaging and oncologic outcomes in patients treated with radical cystectomy without neoadjuvant chemotherapy. Eur. Urol. Focus 4, 245–251 (2018).

    Article  PubMed  Google Scholar 

  20. Panebianco, V. et al. Improving staging in bladder cancer: the increasing role of multiparametric magnetic resonance imaging. Eur. Urol. Focus 2, 113–121 (2016).

    Article  PubMed  Google Scholar 

  21. Woo, S., Suh, C. H., Kim, S. Y., Cho, J. Y. & Kim, S. H. The diagnostic performance of MRI for detection of lymph node metastasis in bladder and prostate cancer: an updated systematic review and diagnostic meta-analysis. AJR Am. J. Roentgenol. 210, W95–W109 (2018).

    Article  PubMed  Google Scholar 

  22. Panebianco, V. et al. Multiparametric magnetic resonance imaging for bladder cancer: development of VI-RADS (Vesical Imaging-Reporting And Data System). Eur. Urol. 74, 294–306 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Green, D. A. et al. Role of magnetic resonance imaging in bladder cancer: current status and emerging techniques. BJU Int. 110, 1463–1470 (2012).

    Article  PubMed  Google Scholar 

  24. Papalia, R. et al. Diffusion-weighted magnetic resonance imaging in patients selected for radical cystectomy: detection rate of pelvic lymph node metastases. BJU Int. 109, 1031–1036 (2012).

    Article  PubMed  Google Scholar 

  25. Wollin, D. A., Deng, F.-M., Huang, W. C., Babb, J. S. & Rosenkrantz, A. B. Conventional and diffusion-weighted MRI features in diagnosis of metastatic lymphadenopathy in bladder cancer. Can. J. Urol. 21, 7454–7459 (2014).

    PubMed  Google Scholar 

  26. Mir, N., Sohaib, S. A., Collins, D. & Koh, D. M. Fusion of high b-value diffusion-weighted and T2-weighted MR images improves identification of lymph nodes in the pelvis. J. Med. Imaging Radiat. Oncol. 54, 358–364 (2010).

    Article  CAS  PubMed  Google Scholar 

  27. Daneshmand, S., Ahmadi, H., Huynh, L. N. & Dobos, N. Preoperative staging of invasive bladder cancer with dynamic gadolinium-enhanced magnetic resonance imaging: results from a prospective study. Urology 80, 1313–1318 (2012).

    Article  PubMed  Google Scholar 

  28. Soubra, A. et al. The diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography and computed tomography in staging bladder cancer: a single-institution study and a systematic review with meta-analysis. World J. Urol. 34, 1229–1237 (2016).

    Article  PubMed  Google Scholar 

  29. Lodde, M. et al. Evaluation of fluorodeoxyglucose positron-emission tomography with computed tomography for staging of urothelial carcinoma. BJU Int. 106, 658–663 (2010).

    Article  PubMed  Google Scholar 

  30. Chakraborty, D. et al. Role of fluorodeoxyglucose positron emission tomography/computed tomography in diagnostic evaluation of carcinoma urinary bladder: comparison with computed tomography. World J. Nucl. Med. 13, 34–39 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Girard, A. et al. Integrated analysis of 18F-FDG PET/CT improves preoperative lymph node staging for patients with invasive bladder cancer. Eur. Radiol. 29, 4286–4293 (2019).

    Article  PubMed  Google Scholar 

  32. Rouanne, M. et al. Potential impact of 18F-FDG PET/CT on patients selection for neoadjuvant chemotherapy before radical cystectomy. Eur. J. Surg. Oncol. 40, 1724–1730 (2014).

    Article  CAS  PubMed  Google Scholar 

  33. Vind-Kezunovic, S. et al. Detection of lymph node metastasis in patients with bladder cancer using maximum standardised uptake value and 18F-fluorodeoxyglucose positron emission tomography/computed tomography: results from a high-volume centre including long-term follow-up. Eur. Urol. Focus 5, 90–96 (2019).

    Article  PubMed  Google Scholar 

  34. Kibel, A. S. et al. Prospective study of [18F]fluorodeoxyglucose positron emission tomography/computed tomography for staging of muscle-invasive bladder carcinoma. J. Clin. Oncol. 27, 4314–4320 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Apolo, A. B. et al. Clinical value of fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in bladder cancer. J. Clin. Oncol. 28, 3973–3978 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Voskuilen, C. S. et al. Staging 18F-fluorodeoxyglucose positron emission tomography/computed tomography changes treatment recommendation in invasive bladder cancer. Eur. Urol. Oncol. 5, 366–369 (2022).

    Article  PubMed  Google Scholar 

  37. Hitier-Berthault, M. et al. 18F-fluorodeoxyglucose positron emission tomography-computed tomography for preoperative lymph node staging in patients undergoing radical cystectomy for bladder cancer: a prospective study. Int J. Urol. 20, 788–796 (2013).

    Article  CAS  PubMed  Google Scholar 

  38. Dason, S. et al. Utility of routine preoperative 18F-fluorodeoxyglucose positron emission tomography/computerized tomography in identifying pathological lymph node metastases at radical cystectomy. J. Urol. 204, 254–259 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Aljabery, F. et al. PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer. BMC Urol. 15, 87 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Pichler, R. et al. Pelvic lymph node staging by combined 18F-FDG-PET/CT imaging in bladder cancer prior to radical cystectomy. Clin. Genitourin. Cancer 15, e387–e395 (2017).

    Article  PubMed  Google Scholar 

  41. Goodfellow, H. et al. Role of fluorodeoxyglucose positron emission tomography (FDG PET)-computed tomography (CT) in the staging of bladder cancer. BJU Int. 114, 389–395 (2014).

    Article  CAS  PubMed  Google Scholar 

  42. Jeong, I. G. et al. FDG PET-CT for lymph node staging of bladder cancer: a prospective study of patients with extended pelvic lymphadenectomy. Ann. Surg. Oncol. 22, 3150–3156 (2015).

    Article  PubMed  Google Scholar 

  43. Ha, H. K., Koo, P. J. & Kim, S.-J. Diagnostic accuracy of F-18 FDG PET/CT for preoperative lymph node staging in newly diagnosed bladder cancer patients: a systematic review and meta-analysis. Oncology 95, 31–38 (2018).

    Article  CAS  PubMed  Google Scholar 

  44. Lambin, P. et al. Radiomics: the bridge between medical imaging and personalized medicine. Nat. Rev. Clin. Oncol. 14, 749–762 (2017).

    Article  PubMed  Google Scholar 

  45. Wu, S. et al. Development and validation of an MRI-based radiomics signature for the preoperative prediction of lymph node metastasis in bladder cancer. EBioMedicine 34, 76–84 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Gresser, E. et al. Radiomics signature using manual versus automated segmentation for lymph node staging of bladder cancer. Eur. Urol. Focus S2405-4569, 00204–00208 (2022).

    Google Scholar 

  47. Harmon, S. A. et al. Multiresolution application of artificial intelligence in digital pathology for prediction of positive lymph nodes from primary tumors in bladder cancer. JCO Clin. Cancer Inform. 4, 367–382 (2020).

  48. Seiler, R. et al. Prediction of lymph node metastasis in patients with bladder cancer using whole transcriptome gene expression signatures. J. Urol. 196, 1036–1041 (2016).

    Article  PubMed  Google Scholar 

  49. Novruzov, E. et al. Head-to-head intra-individual comparison of [68Ga]-FAPI and [18F]-FDG PET/CT in patients with bladder cancer. Mol. Imaging Biol. 24, 651–658 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zhang-Yin, J. et al. PET imaging in bladder cancer: an update and future direction. Pharm. Basel Switz. 16, 606 (2023).

    CAS  Google Scholar 

  51. Powles, T. et al. Bladder cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann. Oncol. 33, 244–258 (2022).

    Article  CAS  PubMed  Google Scholar 

  52. Chang, S. S. et al. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline. J. Urol. 198, 552–559 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Bladder cancer: diagnosis and management of bladder cancer: © NICE (2015) Bladder cancer: diagnosis and management of bladder cancer. BJU Int. 120:755–765 (2017).

  54. Flaig, T. W. et al. Bladder cancer, version 3.2020, NCCN clinical practice guidelines in oncology. J. Natl Compr. Cancer Netw. 18, 329–354 (2020).

    Article  Google Scholar 

  55. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur. Urol. 48, 202–205 (2005). discussion 205–206.

    Article  Google Scholar 

  56. Fahmy, O. et al. A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer. Urol. Oncol. 36, 43–53 (2018).

    Article  PubMed  Google Scholar 

  57. Grossman, H. B. et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N. Engl. J. Med. 349, 859–866 (2003).

    Article  CAS  PubMed  Google Scholar 

  58. Pfister, C. et al. Randomized phase III trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin, or gemcitabine and cisplatin as perioperative chemotherapy for patients with muscle-invasive bladder cancer. analysis of the GETUG/AFU V05 VESPER trial secondary endpoints: chemotherapy toxicity and pathological responses. Eur. Urol. 79, 214–221 (2021).

    Article  CAS  PubMed  Google Scholar 

  59. Iyer, G. et al. Neoadjuvant gemcitabine-cisplatin plus radical cystectomy-pelvic lymph node dissection for muscle-invasive bladder cancer: a 12-year experience. Clin. Genitourin. Cancer 18, 387–394 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Rosenblatt, R. et al. Pathologic downstaging is a surrogate marker for efficacy and increased survival following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive urothelial bladder cancer. Eur. Urol. 61, 1229–1238 (2012).

    Article  PubMed  Google Scholar 

  61. Meijer, R. P. et al. Induction chemotherapy followed by surgery in node positive bladder cancer. Urology 83, 134–139 (2014).

    Article  PubMed  Google Scholar 

  62. Ho, P. L. et al. Outcome of patients with clinically node-positive bladder cancer undergoing consolidative surgery after preoperative chemotherapy: the M.D. Anderson Cancer Center Experience. Urol. Oncol. 34, 59.e1–8 (2016).

    Article  PubMed  Google Scholar 

  63. Urakami, S. et al. Clinical response to induction chemotherapy predicts improved survival outcome in urothelial carcinoma with clinical lymph nodal metastasis treated by consolidative surgery. Int. J. Clin. Oncol. 20, 1171–1178 (2015).

    Article  CAS  PubMed  Google Scholar 

  64. Stanik, M. et al. Clinically node-positive bladder cancer: oncological results of induction chemotherapy and consolidative surgery. Neoplasma 65, 287–291 (2018).

    Article  CAS  PubMed  Google Scholar 

  65. Abrahamsson, J. et al. Complete metabolic response with [18F]fluorodeoxyglucose-positron emission tomography/computed tomography predicts survival following induction chemotherapy and radical cystectomy in clinically lymph node positive bladder cancer. BJU Int. 129, 174–181 (2022).

    Article  PubMed  Google Scholar 

  66. Zargar-Shoshtari, K. et al. A multi-institutional analysis of outcomes of patients with clinically node positive urothelial bladder cancer treated with induction chemotherapy and radical cystectomy. J. Urol. 195, 53–59 (2016).

    Article  PubMed  Google Scholar 

  67. Al-Alao, O. et al. Clinically node-positive (cN+) urothelial carcinoma of the bladder treated with chemotherapy and radical cystectomy: clinical outcomes and development of a postoperative risk stratification model. Urol. Oncol. 38, 76.e19–76.e28 (2020).

    Article  PubMed  Google Scholar 

  68. von Deimling, M. et al. Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node‐positive bladder cancer. BJU International https://doi.org/10.1111/bju.16210 (2023).

  69. Tan, M. P. et al. The intensity-modulated pelvic node and bladder radiotherapy (IMPART) trial: a phase II single-centre prospective study. Clin. Oncol. 32, 93–100 (2020).

    Article  CAS  Google Scholar 

  70. Azuma, H. et al. The novel bladder preservation therapy BOAI-CDDP-radiation (OMC-regimen): a new treatment option for invasive bladder cancer patients with lymph node metastasis. Int. J. Oncol. 44, 1895–1903 (2014).

    Article  CAS  PubMed  Google Scholar 

  71. Bajorin, D. F. et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N. Engl. J. Med. 384, 2102–2114 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Bellmunt, J. et al. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 22, 525–537 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Powles, T. et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N. Engl. J. Med. 383, 1218–1230 (2020).

    Article  CAS  PubMed  Google Scholar 

  74. Bellmunt, J. et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N. Engl. J. Med. 376, 1015–1026 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Lee, C. T. et al. Cystectomy delay more than 3 months from initial bladder cancer diagnosis results in decreased disease specific and overall survival. J. Urol. 175, 1262–1267 (2006).

    Article  PubMed  Google Scholar 

  76. Lucca, I. et al. Adjuvant cisplatin-based combined chemotherapy for lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a retrospective international study of >1500 patients. BJU Int. 115, 722–727 (2015).

    Article  CAS  PubMed  Google Scholar 

  77. Donat, S. M. et al. Potential impact of postoperative early complications on the timing of adjuvant chemotherapy in patients undergoing radical cystectomy: a high-volume tertiary cancer center experience. Eur. Urol. 55, 177–185 (2009).

    Article  PubMed  Google Scholar 

  78. Arora, S. et al. Defining a “High Volume” radical cystectomy hospital: where do we draw the line? Eur. Urol. Focus 6, 975–981 (2020).

    Article  PubMed  Google Scholar 

  79. Advanced Bladder Cancer (ABC) Meta-analysis Collaborators Group. Adjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and meta-analysis of individual participant data from randomised controlled trials. Eur. Urol. 81, 50–61 (2022).

    Article  Google Scholar 

  80. Moschini, M. et al. Surgical treatment for clinical node-positive bladder cancer patients treated with radical cystectomy without neoadjuvant chemotherapy. World J. Urol. 36, 639–644 (2018).

    Article  PubMed  Google Scholar 

  81. Afferi, L. et al. Selecting the best candidates for cisplatin-based adjuvant chemotherapy after radical cystectomy among patients with pN+ bladder cancer. Eur. Urol. Oncol. S2588-9311, 00062–1 (2022).

    Google Scholar 

  82. Hermans, T. J. N. et al. Pathological downstaging and survival after induction chemotherapy and radical cystectomy for clinically node-positive bladder cancer — results of a nationwide population-based study. Eur. J. Cancer 69, 1–8 (2016).

    Article  PubMed  Google Scholar 

  83. Pak, S. et al. Induction chemotherapy followed by surgery versus upfront radical cystectomy in patients with clinically node-positive muscle-invasive bladder cancer. Clin. Genitourin. Cancer 17, e420–e428 (2019).

    Article  PubMed  Google Scholar 

  84. Ghodoussipour, S. et al. Preoperative chemotherapy in clinically node positive muscle invasive bladder cancer: radiologic variables can predict response. Urol. Oncol. 39, 133.e1–133.e8 (2021).

    Article  PubMed  Google Scholar 

  85. Afferi, L. et al. The impact of treatment modality on survival in patients with clinical node-positive bladder cancer: results from a multicenter collaboration. World J. Urol. 39, 443–451 (2021).

    Article  CAS  PubMed  Google Scholar 

  86. von Deimling, M. et al. Carboplatin induction chemotherapy in clinically lymph node–positive bladder cancer. Eur. Urol. Open Sci. 51, 39–46 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Necchi, A. et al. Lack of effectiveness of postchemotherapy lymphadenectomy in bladder cancer patients with clinical evidence of metastatic pelvic or retroperitoneal lymph nodes only: a propensity score-based analysis. Eur. Urol. Focus 5, 242–249 (2019).

    Article  PubMed  Google Scholar 

  88. Haque, W., Verma, V., Butler, E. B. & Teh, B. S. Chemotherapy versus chemoradiation for node-positive bladder cancer: practice patterns and outcomes from the national cancer data base. Bladder Cancer 3, 283–291 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Swinton, M. et al. Bladder-sparing treatment with radical dose radiotherapy is an effective alternative to radical cystectomy in patients with clinically node-positive nonmetastatic bladder cancer. J. Clin. Oncol. 2023:JCO2300725.

  90. Seisen, T. et al. Efficacy of high-intensity local treatment for metastatic urothelial carcinoma of the bladder: a propensity score-weighted analysis from the national cancer data base. J. Clin. Oncol. 34, 3529–3536 (2016).

    Article  PubMed  Google Scholar 

  91. Seisen, T., Rouprêt, M., Trinh, Q.-D. & Bellmunt, J. Re: Martin Swinton, Neethu Billy Graham Mariam, Jean Ling Tan, et al. Bladder-sparing treatment with radical dose radiotherapy is an effective alternative to radical cystectomy in patients with clinically node-positive nonmetastatic bladder cancer. J Clin Oncol. In press. Eur. Urol. S0302-2838, 03163–03169 (2023).

    Google Scholar 

  92. Galsky, M. D. et al. Comparative effectiveness of treatment strategies for bladder cancer with clinical evidence of regional lymph node involvement. J. Clin. Oncol. 34, 2627–2635 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Darwish, C., Sparks, A., Amdur, R., Reddy, A. & Whalen, M. Trends in treatment strategies and comparison of outcomes in lymph node positive bladder cancer: an analysis of the national cancer database. Urology 146, 168–176 (2020).

    Article  PubMed  Google Scholar 

  94. Staník, M. et al. Comparison of different treatment modalities outcomes in clinically node-positive bladder cancer: analysis of a population-based cancer registry. Clin. Genitourin. Cancer 17, e759–e767 (2019).

    Article  PubMed  Google Scholar 

  95. Bae, W. K. et al. Comparative effectiveness of palliative chemotherapy versus neoadjuvant chemotherapy followed by radical cystectomy versus cystectomy followed by adjuvant chemotherapy versus cystectomy for regional node-positive bladder cancer: a retrospective analysis: KCSG GU 17-03. Cancer Med. 8, 5431–5437 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Powles, T. et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat. Med. 25, 1706–1714 (2019).

    Article  CAS  PubMed  Google Scholar 

  97. Necchi, A. et al. Pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive urothelial bladder carcinoma (PURE-01): an open-label, single-arm, phase II study. J. Clin. Oncol. 36, 3353–3360 (2018).

    Article  CAS  PubMed  Google Scholar 

  98. Rose, T. L. et al. Phase II study of gemcitabine and split-dose cisplatin plus pembrolizumab as neoadjuvant therapy before radical cystectomy in patients with muscle-invasive bladder cancer. J. Clin. Oncol. 39, 3140–3148 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Funt, S. A. et al. Neoadjuvant atezolizumab with gemcitabine and cisplatin in patients with muscle-invasive bladder cancer: a multicenter, single-arm, phase II trial. J. Clin. Oncol. 40, 1312–1322 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. M.D. Anderson Cancer Center. Durvalumab and Standard Chemotherapy for the Treatment of Lymph Node Positive Bladder Cancer (2023). https://clinicaltrials.gov/study/NCT05137262 (accessed 1 January 2023).

  101. ClinicalTrials.gov. National Cancer Institute (NCI). Phase II Study of Bladder-SparIng ChemoradiatioN With Durvalumab in Clinical Stage III, Node PosItive BladdeR CancEr (INSPIRE) (2023). https://clinicaltrials.gov/study/NCT05137262 (accessed 1 January 2023).

  102. Woldu S. Checkpoint Inhibitor and Radiation Therapy in Bulky, Node-Positive Bladder Cancer (CIRTiN-BC): A Phase II, Single-Arm Trial (2023). https://clinicaltrials.gov/study/NCT04779489 (accessed 1 January 2023).

  103. ClinicalTrials.gov. Memorial Sloan Kettering Cancer Center. Enfortumab Vedotin in Combination With Pembrolizumab for Locally Advanced and/or Node Positive Urothelial Carcinoma Prior to Surgery (EV-ECLIPSE) (2023). https://clinicaltrials.gov/study/NCT05239624 (accessed 1 January 2023).

  104. Powles, T. et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N. Engl. J. Med. 384, 1125–1135 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Sorbonne University, GRC 5, Predictive Onco-Urology, APHP, Pitié-Salpêtrière Hospital, Urology, 75013, Paris, France

    Elisabeth Grobet-Jeandin, Louis Lenfant, Ugo Pinar, Jérôme Parra, Pierre Mozer, Morgan Rouprêt & Thomas Seisen

  2. Division of Urology, Geneva University Hospitals, Geneva, Switzerland

    Elisabeth Grobet-Jeandin

  3. Sorbonne University, GRC 5, Predictive Onco-Urology, APHP, Pitié-Salpêtrière Hospital, Radiology, 75013, Paris, France

    Raphaele Renard-Penna

  4. Department of medical oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, AP-HP centre, Paris, France

    Constance Thibault

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Contributions

T.S., E.G.-J., L.L. and U.P. researched data for the article. All authors contributed substantially to discussion of the content. T.S. and E.G.-J. wrote the article. T.S., E.G.-J. and M.R. reviewed and/or edited the manuscript before submission.

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Correspondence to Thomas Seisen.

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Nature Reviews Urology thanks M. Perera, W. Krajewski and M. Khan for their contribution to the peer review of this work.

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Grobet-Jeandin, E., Lenfant, L., Pinar, U. et al. Management of patients with muscle-invasive bladder cancer with clinical evidence of pelvic lymph node metastases. Nat Rev Urol (2024). https://doi.org/10.1038/s41585-023-00842-y

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