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Development and Validation of a Model for Predicting Intravesical Recurrence in Organ-confined Upper Urinary Tract Urothelial Carcinoma Patients after Radical Nephroureterectomy: a Retrospective Study in One Center with Long-term Follow-up

  • Original Article
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Pathology & Oncology Research

Abstract

Although radical nephroureterectomy is the standard treatment method for upper urinary tract urothelial carcinoma, it is associated with a high risk of intravesical recurrence. There are no models for predicting IVR after RNU in patients with organ-confined UTUC. Therefore, we developed and validated a model for postoperative prediction of IVR after RNU. The development cohort consisted of 416 patients who underwent RNU with bladder cuff excision at our center between 1 January 2007 and 31 December 2015. Patient clinicopathologic data were recorded. Multivariate Cox proportional hazard ratio regression was used to build a predictive model with regression coefficients, backward step-wise selection was applied, and the likelihood ratio test with Akaike’s information criterion was used as the stopping rule. An independent cohort consisting of 152 consecutive patients from 1 January 2016 and 31 December 2017 was used for validation. The performance of this predictive model was assessed with respect to discrimination, calibration, and clinical usefulness. The predictors in this model included tumor stage, tumor diameter, tumor location, and tumor grade. In the validation cohort, the model showed good discrimination, with a concordance index of 0.689 (95% CI, 0.629 to 0.748) and good calibration. Decision curve analysis demonstrated that the model was also clinically useful. This study presents a good model that may facilitate individualized postoperative prediction of IVR after RNU in patients with organ-confined UTUC, and thus, may help improve postoperative strategies and facilitate treatment outcomes.

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References

  1. Munoz JJ, Ellison LM (2000) Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J Urol 164(5):1523–1525

    CAS  PubMed  Google Scholar 

  2. Roupret M, Colin P, Yates DR (2014) A new proposal to risk stratify urothelial carcinomas of the upper urinary tract (UTUCs) in a predefinitive treatment setting: low-risk versus high-risk UTUCs. Eur Urol 66(2):181–183

    PubMed  Google Scholar 

  3. Soria F, Shariat SF, Lerner SP, Fritsche HM, Rink M, Kassouf W, Spiess PE, Lotan Y, Ye D, Fernández MI, Kikuchi E, Chade DC, Babjuk M, Grollman AP, Thalmann GN (2017) Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC). World J Urol 35(3):379–387

    PubMed  Google Scholar 

  4. Abouassaly R, Alibhai SM, Shah N, Timilshina N, Fleshner N, Finelli A (2010) Troubling outcomes from population-level analysis of surgery for upper tract urothelial carcinoma. Urology 76(4):895–901

    PubMed  Google Scholar 

  5. Jeldres C, Sun M, Isbarn H, Lughezzani G, Budäus L, Alasker A, Shariat SF, Lattouf JB, Widmer H, Pharand D, Arjane P, Graefen M, Montorsi F, Perrotte P, Karakiewicz PI (2010) A population-based assessment of perioperative mortality after nephroureterectomy for upper-tract urothelial carcinoma. Urology 75(2):315–320

    PubMed  Google Scholar 

  6. Lughezzani G, Burger M, Margulis V, Matin SF, Novara G, Roupret M, Shariat SF, Wood CG, Zigeuner R (2012) Prognostic factors in upper urinary tract urothelial carcinomas: a comprehensive review of the current literature. Eur Urol 62(1):100–114

    PubMed  Google Scholar 

  7. Xylinas E, Kluth L, Passoni N, Trinh QD, Rieken M, Lee RK, Fajkovic H, Novara G, Margulis V, Raman JD, Lotan Y, Rouprêt M, Aziz A, Fritsche HM, Weizer A, Martinez-Salamanca JI, Matsumoto K, Seitz C, Remzi M, Walton T, Karakiewicz PI, Montorsi F, Zerbib M, Scherr DS, Shariat SF, UTUC Collaboration (2014) Prediction of intravesical recurrence after radical nephroureterectomy: development of a clinical decision-making tool. Eur Urol 65(3):650–658

    PubMed  Google Scholar 

  8. Geneva (1997) Guidelines for controlling and monitoring the tobacco epidemic. World Health Organization, Geneva

  9. Hoang ML, Chen CH, Sidorenko VS, He J, Dickman KG, Yun BH, Moriya M, Niknafs N, Douville C, Karchin R, Turesky RJ, Pu YS, Vogelstein B, Papadopoulos N, Grollman AP, Kinzler KW, Rosenquist TA (2013) Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing. Sci Transl Med 5(197): 197ra102

  10. Colin P, Ouzzane A, Pignot G, Ravier E, Crouzet S, Ariane MM, Audouin M, Neuzillet Y, Albouy B, Hurel S, Saint F, Guillotreau J, Guy L, Bigot P, De La Taille A, Arroua F, Marchand C, Matte A, Fais PO, Rouprêt M, French Collaborative National Database on U.U.T.-U.C (2012) Comparison of oncological outcomes after segmental ureterectomy or radical nephroureterectomy in urothelial carcinomas of the upper urinary tract: results from a large French multicentre study. BJU Int 110(8):1134–1141

    PubMed  Google Scholar 

  11. Siegel RL, Miller KD, Jemal A (2017) Cancer Statistics, 2017. CA Cancer J Clin 67(1):7–30

    Google Scholar 

  12. Lughezzani G, Jeldres C, Isbarn H, Sun M, Shariat SF, Alasker A, Pharand D, Widmer H, Arjane P, Graefen M, Montorsi F, Perrotte P, Karakiewicz PI (2009) Nephroureterectomy and segmental ureterectomy in the treatment of invasive upper tract urothelial carcinoma: a population-based study of 2299 patients. Eur J Cancer 45(18):3291–3297

    PubMed  Google Scholar 

  13. von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M (2005) Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23(21):4602–4608

    PubMed  Google Scholar 

  14. Collins GS, Reitsma JB, Altman DG, Moons KG (2015) Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. BMJ 350:g7594

    PubMed  Google Scholar 

  15. Sauerbrei W, Boulesteix AL, Binder H (2011) Stability investigations of multivariable regression models derived from low- and high-dimensional data. J Biopharm Stat 21(6):1206–1231

    PubMed  Google Scholar 

  16. Raman JD, Ng CK, Boorjian SA, Vaughan ED Jr, Sosa RE, Scherr DS (2005) Bladder cancer after managing upper urinary tract transitional cell carcinoma: predictive factors and pathology. BJU Int 96(7):1031–1035

    PubMed  Google Scholar 

  17. Zigeuner RE, Hutterer G, Chromecki T, Rehak P, Langner C (2006) Bladder tumour development after urothelial carcinoma of the upper urinary tract is related to primary tumour location. BJU Int 98(6):1181–1186

    PubMed  Google Scholar 

  18. Novara G, De Marco V, Dalpiaz O, Gottardo F, Bouygues V, Galfano A, Martignoni G, Patard JJ, Artibani W, Ficarra V (2008) Independent predictors of metachronous bladder transitional cell carcinoma (TCC) after nephroureterectomy for TCC of the upper urinary tract. BJU Int 101(11):1368–1374

    PubMed  Google Scholar 

  19. Seisen T, Granger B, Colin P, Léon P, Utard G, Renard-Penna R, Compérat E, Mozer P, Cussenot O, Shariat SF, Rouprêt M (2015) A Systematic Review and Meta-analysis of Clinicopathologic Factors Linked to Intravesical Recurrence After Radical Nephroureterectomy to Treat Upper Tract Urothelial Carcinoma. Eur Urol 67(6):1122–1133

    PubMed  Google Scholar 

  20. Terakawa T, Miyake H, Muramaki M, Takenaka A, Hara I, Fujisawa M (2008) Risk factors for intravesical recurrence after surgical management of transitional cell carcinoma of the upper urinary tract. Urology 71(1):123–127

    PubMed  Google Scholar 

  21. Hisataki T, Miyao N, Masumori N, Takahashi A, Sasai M, Yanase M, Itoh N, Tsukamoto T (2000) Risk factors for the development of bladder cancer after upper tract urothelial cancer. Urology 55(5):663–667

    CAS  PubMed  Google Scholar 

  22. Rouprêt M, Babjuk M, Compérat E, Zigeuner R, Sylvester RJ, Burger M, Cowan NC, Böhle A, Van Rhijn BW, Kaasinen E, Palou J, Shariat SF (2015) European Association of Urology Guidelines on Upper Urinary Tract Urothelial Cell Carcinoma: 2015 Update. Eur Urol 68(5):868–879

    PubMed  Google Scholar 

  23. Espiritu PN, Sverrisson EF, Sexton WJ, Pow-Sang JM, Poch MA, Dhillon J, Spiess PE (2014) Effect of tumor size on recurrence-free survival of upper tract urothelial carcinoma following surgical resection. Urol Oncol 32(5):619–624

    PubMed  Google Scholar 

  24. Cho YH, Seo YH, Chung SJ, Hwang I, Yu HS, Kim SO, Jung SI, Kang TW, Kwon DD, Park K, Hwang JE, Heo SH, Kim GS, Hwang EC (2014) Predictors of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma: an inflammation-based prognostic score. Korean J Urol 55(7):453–459

    PubMed  PubMed Central  Google Scholar 

  25. Narukawa T, Hara T, Arai E, Komiyama M, Kawahara T, Kanai Y, Fujimoto H (2015) Tumour multifocality and grade predict intravesical recurrence after nephroureterectomy in patients with upper urinary tract urothelial carcinoma without a history of bladder cancer. Jpn J Clin Oncol 45(5):488–493

    PubMed  Google Scholar 

  26. Harris AL, Neal DE (1992) Bladder cancer--field versus clonal origin. N Engl J Med 326(11):759–761

    CAS  PubMed  Google Scholar 

  27. Hinotsu S, Akaza H, Ohashi Y, Kotake T (1999) Intravesical chemotherapy for maximum prophylaxis of new early phase superficial bladder carcinoma treated by transurethral resection: a combined analysis of trials by the Japanese Urological Cancer Research Group using smoothed hazard function. Cancer 86(9):1818–1826

    CAS  PubMed  Google Scholar 

  28. Elawdy MM, Osman Y, Taha DE, Zahran MH, El-Halwagy S, Garba ME, Harraz AM (2017) Risk factors and prognosis of intravesical recurrence after surgical management of upper tract urothelial carcinoma: A 30-year single centre experience. Arab J Urol 15(3):216–222

    PubMed  PubMed Central  Google Scholar 

  29. Li WM, Wu WJ, Li CC, Ke HL, Wei YC, Yeh HC, Chou YH, Huang CH, Huang CN (2013) The effect of tumor location on prognosis in patients with primary ureteral urothelial carcinoma. Urol Oncol 31(8):1670–1675

    PubMed  Google Scholar 

  30. Novara G, De Marco V, Gottardo F, Dalpiaz O, Bouygues V, Galfano A, Martignoni G, Patard JJ, Artibani W, Ficarra V (2007) Independent predictors of cancer-specific survival in transitional cell carcinoma of the upper urinary tract: multi-institutional dataset from 3 European centers. Cancer 110(8):1715–1722

    PubMed  Google Scholar 

  31. Boorjian S, Ugras S, Mongan NP, Gudas LJ, You X, Tickoo SK, Scherr DS (2004) Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer. Urology 64(2):383–388

    PubMed  Google Scholar 

  32. Shen SS, Smith CL, Hsieh JT, Yu J, Kim IY, Jian W, Sonpavde G, Ayala GE, Younes M, Lerner SP (2006) Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer 106(12):2610–2616

    CAS  PubMed  Google Scholar 

  33. Kluth LA, Rieken M, Xylinas E, Kent M, Rink M, Rouprêt M, Sharifi N, Jamzadeh A, Kassouf W, Kaushik D, Boorjian SA, Roghmann F, Noldus J, Masson-Lecomte A, Vordos D, Ikeda M, Matsumoto K, Hagiwara M, Kikuchi E, Fradet Y, Izawa J, Rendon R, Fairey A, Lotan Y, Bachmann A, Zerbib M, Fisch M, Scherr DS, Vickers A, Shariat SF (2014) Gender-specific differences in clinicopathologic outcomes following radical cystectomy: an international multi-institutional study of more than 8000 patients. Eur Urol 66(5):913–919

    PubMed  Google Scholar 

  34. Pignot G, Colin P, Zerbib M, Audenet F, Soulié M, Hurel S, Delage F, Irani J, Descazeaud A, Droupy S, Rozet F, Phé V, Ruffion A, Long JA, Crouzet S, Houlgatte A, Bigot P, Guy L, Faïs PO, Rouprêt M French Collaborative National Database on UUT-UC (2014) Influence of previous or synchronous bladder cancer on oncologic outcomes after radical nephroureterectomy for upper urinary tract urothelial carcinoma. Urol Oncol 32(1):23 e1-e8

  35. Akdogan B, Dogan HS, Eskicorapci SY, Sahin A, Erkan I, Ozen H (2006) Prognostic significance of bladder tumor history and tumor location in upper tract transitional cell carcinoma. J Urol 176(1):48–52

    PubMed  Google Scholar 

  36. Sung HH, Jeon HG, Han DH, Jeong BC, Seo SI, Lee HM, Choi HY, Jeon SS (2015) Diagnostic Ureterorenoscopy Is Associated with Increased Intravesical Recurrence following Radical Nephroureterectomy in Upper Tract Urothelial Carcinoma. PLoS One 10(11):e0139976

    PubMed  PubMed Central  Google Scholar 

  37. Fradet V, Mauermann J, Kassouf W, Rendon R, Jacobsen N, Fairey A, Izawa J, Kapoor A, Black P, Tanguay S, Chin J, So A, Lattouf JB, Bell D, Saad F, Sheyegan B, Drachenberg D, Cagiannos I, Lacombe L (2014) Risk factors for bladder cancer recurrence after nephroureterectomy for upper tract urothelial tumors: results from the Canadian Upper Tract Collaboration. Urol Oncol 32(6):839–845

    PubMed  Google Scholar 

  38. Hagiwara M, Kikuchi E, Tanaka N, Matsumoto K, Ide H, Miyajima A, Masuda T, Nakamura S, Oya M (2013) Impact of smoking status on bladder tumor recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. J Urol 189(6):2062–2068

    PubMed  Google Scholar 

  39. Xylinas E, Kluth LA, Rieken M, Lee RK, Elghouayel M, Ficarra V, Margulis V, Lotan Y, Rouprêt M, Martinez-Salamanca JI, Matsumoto K, Seitz C, Karakiewicz PI, Zerbib M, Scherr DS, Shariat SF, UTUC Collaboration (2014) Impact of smoking status and cumulative exposure on intravesical recurrence of upper tract urothelial carcinoma after radical nephroureterectomy. BJU Int 114(1):56–61

    PubMed  Google Scholar 

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Acknowledgments

This study was financially supported (MC05) through the Shengjing Hospital Science and Technology Program. We give special thanks to all the teachers at the Department of Urology of Shengjing Hospital for their help and support.

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Song Bai had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Song Bai.

Acquisition of data, analysis and interpretation of data: Song Bai, Xuanyu Zhang .

Drafting of the manuscript and critical revision of the manuscript for important intellectual content: Xuanyu Zhang.

Statistical analysis: Xuanyu Zhang.

Obtaining funding and other (figures): Song Bai.

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Correspondence to Song Bai.

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Song Bai certifies that all conflicts of interest, including specific financial interests, relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending) are none.

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Zhang, X., Bu, R., Liu, Z. et al. Development and Validation of a Model for Predicting Intravesical Recurrence in Organ-confined Upper Urinary Tract Urothelial Carcinoma Patients after Radical Nephroureterectomy: a Retrospective Study in One Center with Long-term Follow-up. Pathol. Oncol. Res. 26, 1741–1748 (2020). https://doi.org/10.1007/s12253-019-00748-4

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  • DOI: https://doi.org/10.1007/s12253-019-00748-4

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