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Neoadjuvant chemotherapy for muscle-invasive bladder cancer: does variant histology matter?

  • Urology - Original Paper
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Abstract

Purpose

The most frequent histology of bladder tumors is urothelial carcinoma. Most are pure urothelial carcinomas (PUC) but up to one-third of the cases present variant histological (VH) features. The aim of this study was to evaluate the role of variant histology in neoadjuvant chemotherapy (NAC) response in patients with urothelial muscle-invasive bladder cancer.

Methods

We retrospectively analyzed data from 77 patients with bladder cancer who performed neoadjuvant chemotherapy at two institutions.

Results

Complete pathological response (ypT0) was higher in patients with PUC (38.5%), comparing with VH (12%). Logistic regression analysis demonstrated that variant histology is associated with an 89% lesser likelihood of tumor downstaging, with advanced clinical T stages and positive smoking history as independent predictors. The estimated mean cancer-specific survival was 68.91 months for PUC patients and 50.23 months for VH patients (log rank test, P = 0.024). Multivariate Cox regression analysis demonstrated that VH and clinical T stage were independent predictors of cancer-specific survival, indicating a worse outcome for patients with VH and advanced clinical T stages.

Conclusions

There are only a few retrospective studies evaluating the clinical impact of variant histology tumors, which are mainly managed as PUC. Our results demonstrate that VH is associated with a worse likelihood of tumor downstaging after NAC and a worse cancer-specific survival in bladder cancer patients. There is a need for further studies and genetic analysis to identify the patients most likely to achieve ypT0 status and downstaging after NAC.

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References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer statistics, 2021. CA Cancer J Clin 71(1):7–33

    Article  PubMed  Google Scholar 

  2. Witjes JA, Bruins HM, Cathomas R, Compérat EM, Cowan NC, Gakis G, Hernández V, Linares Espinós E, Lorch A, Neuzillet Y, Rouanne M, Thalmann GN, Veskimäe E, Ribal MJ, van der Heijden AG (2021) European association of urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2020 guidelines. Eur Urol 79(1):82–104

    Article  CAS  PubMed  Google Scholar 

  3. Moschini M, Dell’Oglio P, Luciano R, Gandaglia G, Soria F, Mattei A, Klatte T, Damiano R, Shariat SF, Salonia A, Montorsi F, Briganti A, Colombo R, Gallina A (2017) Incidence and effect of variant histology on oncological outcomes in patients with bladder cancer treated with radical cystectomy. Urol Oncol 35(6):335–341

    Article  PubMed  Google Scholar 

  4. Lobo N, Shariat SF, Guo CC, Fernandez MI, Kassouf W, Choudhury A, Gao J, Williams SB, Galsky MD, Taylor JA 3rd, Roupret M, Kamat AM (2020) What is the significance of variant histology in urothelial carcinoma? Eur Urol Focus 6(4):653–663

    Article  PubMed  Google Scholar 

  5. Epaillard N, Parent P, Loriot Y, Lavaud P, Vera-Cea EB, Martinez-Chanza N, Rodriguez-Vida A, Dumont C, Lozano R, Llacer C, Ratta R, Oudard S, Thibault C, Auclin E (2021) Treatments outcomes in histological variants and non-urothelial bladder cancer: results of a multicenter retrospective study. Front Oncol 11:671969

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lopez-Beltran A, Henriques V, Montironi R, Cimadamore A, Raspollini MR, Cheng L (2019) Variants and new entities of bladder cancer. Histopathology 74(1):77–96

    Article  PubMed  Google Scholar 

  7. Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: prostate and bladder tumours. Eur Urol 70(1):106–119

    Article  PubMed  Google Scholar 

  8. Hajiran A, Azizi M, Aydin AM, Zemp L, Peyton CC, Dhillon J, Nealon S, Reich RR, Cao B, Li R, Manley BJ, Sexton WJ, Gilbert SM (2021) Pathological and survival outcomes associated with variant histology bladder cancers managed by cystectomy with or without neoadjuvant chemotherapy. J Urol 205(1):100–108

    Article  PubMed  Google Scholar 

  9. Minato A, Fujimoto N, Kubo T (2017) Squamous differentiation predicts poor response to cisplatin-based chemotherapy and unfavorable prognosis in urothelial carcinoma of the urinary bladder. Clin Genitourin Cancer 15(6):e1063–e1067

    Article  PubMed  Google Scholar 

  10. Leite KRM, Borges LL, Filho LR, Chade D, Coelho RF, Cordeiro M, Srougi M, Nahas WC (2021) Histological variants of urothelial carcinoma predict no response to neoadjuvant chemotherapy. Clin Genitourin Cancer 20(1):E1–E6

    Article  PubMed  Google Scholar 

  11. Pokuri VK, Syed JR, Yang Z, Field EP, Cyriac S, Pili R, Levine EG, Azabdaftari G, Trump DL, Guru K, George S (2016) Predictors of complete pathologic response (pT0) to neoadjuvant chemotherapy in muscle-invasive bladder carcinoma. Clin Genitourin Cancer 14(1):e59-65

    Article  PubMed  Google Scholar 

  12. Scosyrev E, Ely BW, Messing EM, Speights VO, Grossman HB, Wood DP, de Vere White RW, Vogelzang NJ, Trump DL, Natale RB, Tangen CM, Crawford ED, Thompson IM (2011) Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest oncology group-directed intergroup study (S8710). BJU Int 108(5):693–699

    Article  CAS  PubMed  Google Scholar 

  13. Veskimae E, Espinos EL, Bruins HM, Yuan Y, Sylvester R, Kamat AM, Shariat SF, Witjes JA, Comperat EM (2019) What is the prognostic and clinical importance of urothelial and nonurothelial histological variants of bladder cancer in predicting oncological outcomes in patients with muscle-invasive and metastatic bladder cancer? A European association of urology muscle invasive and metastatic bladder cancer guidelines panel systematic review. Eur Urol Oncol 2(6):625–642

    Article  PubMed  Google Scholar 

  14. Minato A, Noguchi H, Tomisaki I, Fukuda A, Kubo T, Nakayama T, Fujimoto N (2018) Clinical significance of squamous differentiation in urothelial carcinoma of the bladder. Cancer Control 25(1):1073274818800269

    Article  PubMed  PubMed Central  Google Scholar 

  15. Liu Y, Bui MM, Xu B (2017) Urothelial carcinoma with squamous differentiation is associated with high tumor stage and pelvic lymph-node metastasis. Cancer Control 24(1):78–82

    Article  PubMed  Google Scholar 

  16. Zargar-Shoshtari K, Sverrisson EF, Sharma P, Gupta S, Poch MA, Pow-Sang JM, Spiess PE, Sexton WJ (2016) Clinical outcomes after neoadjuvant chemotherapy and radical cystectomy in the presence of urothelial carcinoma of the bladder with squamous or glandular differentiation. Clin Genitourin Cancer 14(1):82–88

    Article  PubMed  Google Scholar 

  17. Mitra AP, Fairey AS, Skinner EC, Boorjian SA, Frank I, Schoenberg MP, Bivalacqua TJ, Hyndman ME, Reese AC, Steinberg GD, Large MC, van de Hulsbergen- Kaa CA, Bruins HM, Daneshmand S (2019) Implications of micropapillary urothelial carcinoma variant on prognosis following radical cystectomy: a multi-institutional investigation. Urol Oncol 37(1):48–56

    Article  PubMed  Google Scholar 

  18. Sui W, Matulay JT, James MB, Onyeji IC, Theofanides MC, RoyChoudhury A, DeCastro GJ, Wenske S (2016) Micropapillary bladder cancer: insights from the national cancer database. Bladder Cancer 2(4):415–423

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kamat AM, Dinney CP, Gee JR, Grossman HB, Siefker-Radtke AO, Tamboli P, Detry MA, Robinson TL, Pisters LL (2007) Micropapillary bladder cancer: a review of the University of Texas M. D. Anderson cancer center experience with 100 consecutive patients. Cancer 110(1):62–67

    Article  PubMed  Google Scholar 

  20. Abufaraj M, Foerster B, Schernhammer E, Moschini M, Kimura S, Hassler MR, Preston MA, Karakiewicz PI, Remzi M, Shariat SF (2019) Micropapillary urothelial carcinoma of the bladder: a systematic review and meta-analysis of disease characteristics and treatment outcomes. Eur Urol 75(4):649–658

    Article  PubMed  Google Scholar 

  21. Li Q, Assel M, Benfante NE, Pietzak EJ, Herr HW, Donat M, Cha EK, Donahue TF, Bochner BH, Dalbagni G (2019) The impact of plasmacytoid variant histology on the survival of patients with urothelial carcinoma of bladder after radical cystectomy. Eur Urol Focus 5(1):104–108

    Article  PubMed  Google Scholar 

  22. Diamantopoulos LN, Khaki AR, Vakar-Lopez F, Tretiakova MS, Gore JL, Schade GR, Psutka SP, Hsieh AC, Lee JK, Yezefski T, Schweizer MT, Cheng HH, Yu EY, Grivas P, Montgomery RB, Wright JL (2019) Patient (pt) characteristics, treatment patterns, outcomes and prognostic factors in plasmacytoid urothelial carcinoma (PUC). J Clin Oncol 37:e16007–e16007

    Article  Google Scholar 

  23. Ericson KJ, Thomas L, Lee BH (2019) Plasmacytoid variant urothelial carcinoma: Clinicopathologic outcomes and experience with neoadjuvant chemotherapy. J Clin Oncol 37:483–483

    Article  Google Scholar 

  24. Wright JL, Black PC, Brown GA, Porter MP, Kamat AM, Dinney CP, Lin DW (2007) Differences in survival among patients with sarcomatoid carcinoma, carcinosarcoma and urothelial carcinoma of the bladder. J Urol 178(6):2302–2306

    Article  PubMed  Google Scholar 

  25. Vetterlein MW, Wankowicz SAM, Seisen T, Lander R, Loppenberg B, Chun FK, Menon M, Sun M, Barletta JA, Choueiri TK, Bellmunt J, Trinh QD, Preston MA (2017) Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology. Cancer 123(22):4346–4355

    Article  CAS  PubMed  Google Scholar 

  26. Lopez Beltran A, Montironi R, Cheng L (2014) Microcystic urothelial carcinoma: morphology, immunohistochemistry and clinical behaviour. Histopathology 64(6):872–879

    Article  PubMed  Google Scholar 

  27. Linder BJ, Frank I, Cheville JC, Thompson RH, Thapa P, Tarrell RF, Boorjian SA (2013) Outcomes following radical cystectomy for nested variant of urothelial carcinoma: a matched cohort analysis. J Urol 189(5):1670–1675

    Article  PubMed  Google Scholar 

  28. Mai KT, Bateman J, Djordjevic B, Flood TA, Belanger EC (2017) Clear cell urothelial carcinoma. Int J Surg Pathol 25(1):18–25

    Article  PubMed  Google Scholar 

  29. Yang AW, Pooli A, Lele SM, Kim IW, Davies JD, LaGrange CA (2017) Lymphoepithelioma-like, a variant of urothelial carcinoma of the urinary bladder: a case report and systematic review for optimal treatment modality for disease-free survival. BMC Urol 17(1):34

    Article  PubMed  PubMed Central  Google Scholar 

  30. Bhindi B, Frank I, Mason RJ, Tarrell RF, Thapa P, Cheville JC, Costello BA, Pagliaro LC, Karnes RJ, Thompson RH, Tollefson MK, Boorjian SA (2017) Oncologic outcomes for patients with residual cancer at cystectomy following neoadjuvant chemotherapy: a pathologic stage-matched analysis. Eur Urol 72(5):660–664

    Article  PubMed  Google Scholar 

  31. Voskuilen CS, Oo HZ, Genitsch V, Smit LA, Vidal A, Meneses M, Necchi A, Colecchia M, Xylinas E, Fontugne J, Sibony M, Roupret M, Lenfant L, Cote JF, Buser L, Saba K, Furrer MA, van der Heijden MS, Daugaard M, Black PC, van Rhijn BWG, Hendricksen K, Poyet C, Seiler R (2019) Multicenter validation of histopathologic tumor regression grade after neoadjuvant chemotherapy in muscle-invasive bladder carcinoma. Am J Surg Pathol 43(12):1600–1610

    Article  PubMed  Google Scholar 

  32. Fleischmann A, Thalmann GN, Perren A, Seiler R (2014) Tumor regression grade of urothelial bladder cancer after neoadjuvant chemotherapy: a novel and successful strategy to predict survival. Am J Surg Pathol 38(3):325–332

    Article  PubMed  Google Scholar 

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Funding

The authors did not receive support from any organization for the submitted work.

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Authors and Affiliations

Authors

Contributions

Conceptualization: RC, LA, and RP; methodology: RC, LA, IB, and RF; data acquisition: DP and JP; analysis: RC, FL, MC, TC, and AC; investigation and data curation: SM, VS, and RP; writing—original draft preparation: RC, GC, and FCR; supervision: AM and RP; all authors read, revised and approved the final version of the manuscript.

Corresponding author

Correspondence to Raquel Catarino.

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The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

Ethical approval was waived by the local Ethics Committee of Pedro Hispano Hospital in view of the retrospective nature of the study and all the procedures being performed were part of the routine care.

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Catarino, R., Alves, L., Pereira, D. et al. Neoadjuvant chemotherapy for muscle-invasive bladder cancer: does variant histology matter?. Int Urol Nephrol 54, 3163–3169 (2022). https://doi.org/10.1007/s11255-022-03358-3

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  • DOI: https://doi.org/10.1007/s11255-022-03358-3

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