Are there differences between de novo and secondary upper tract urothelial carcinoma tumors?

  • Hanan Goldberg Urology Division, Surgical Oncology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto http://orcid.org/0000-0002-5777-2138
  • Douglas C. Cheung Urology Division, Surgical Oncology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
  • Thenappan Chandrasekar Urology Division, Surgical Oncology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
  • Zachary Klaassen Urology Division, Surgical Oncology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
  • Christopher J.D. Wallis Urology Division, Surgical Oncology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
  • Girish S. Kulkarni Urology Division, Surgical Oncology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
  • Rashid Sayyid Urology Division, Surgical Oncology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
  • Andrew Evans Pathology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
  • Mehdi Masoomian Pathology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
  • Bharati Bapat Department of Laboratory Medicine and Pathobiology, University of Toronto; Lunenfeld Tanenbaum Research Institute, Sinai Health System
  • Theodorus van der Kwast Pathology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
  • Robert J. Hamilton Urology Division, Surgical Oncology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
  • Alexandre Zlotta Urology Division, Surgical Oncology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
  • Neil Fleshner Urology Division, Surgical Oncology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
Keywords: De-novo upper tract urothelial carcinoma, Secondary upper tract urothelial carcinoma, Carcinoma in situ, Recurrence, cancer specific survival

Abstract

Introduction: Upper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers. We aimed to ascertain the clinical differences between UTUC tumous presenting de novo (DnUTUC) and those presenting secondary (SUTUC) following a bladder cancer diagnosis.

Methods: Our institutional database was queried for all UTUC patients who were surgically treated with radical nephroureterectomy or ureterectomy between 2003 and 2017. Bladder recurrence and cancer-specific mortality were compared. To reduce the possible bias due to confounding variables obtained from a simple comparison of outcomes, DnUTUC patients were matched (for age, gender, tumor location, type of surgery, grade, TNM staging, presence of carcinoma in situ, and lymphovascular invasion) with propensity score to SUTUC patients. Bladder recurrence and cancer-specific mortality were assessed with Cox proportional hazards model.

Results: A total of 117 UTUC patients were identified: 80 with DnUTUC (68.4%) and 37 with SUTUC (31.6%). A greater proportion of males with SUTUC was demonstrated (89.2% vs. 68.8; p=0.02). In both groups, 67.5% of patients had high-grade disease but SUTUC demonstrated a higher carcinoma in situ rate (43.2% vs. 25%; p=0.047). Univariate analysis demonstrated that the fiveyear bladder recurrence rate was trending to be higher in SUTUC (65.3% vs. 20.5%; p=0.099). In the Cox model, however, it was associated with increased bladder recurrence (hazard ratio [HR] 3.69; 95% confidence interval [CI] 1.68–8.09; p=0.001). Although univariate analysis demonstrated that SUTUC patients were more likely to die of their disease (30.6% vs. 9%; p=0.009), the multivariable Cox model did not demonstrate this association. The limitations of this study include its retrospective, single-center design and relatively small cohort of patients.

Conclusions: In this hypothesis-generating study, some evidence suggests that further research is needed to delineate differences between SUTUC and DnUTUC.

Author Biography

Hanan Goldberg, Urology Division, Surgical Oncology Department, Princess Margaret Cancer Centre, University Health Network, University of Toronto
Uro-oncology fellow (SUO), Princess Margaret Cancer Centre, University Health Network, University of Toronto

References

References:

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer journal for clinicians 2016; 66(1): 7-30.

Munoz JJ, Ellison LM. Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. The Journal of urology 2000; 164(5): 1523-5.

Shariat SF, Favaretto RL, Gupta A, et al. Gender differences in radical nephroureterectomy for upper tract urothelial carcinoma. World journal of urology 2011; 29(4): 481-6.

Roupret M, Babjuk M, Comperat E, et al. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2017 Update. European urology 2018; 73(1): 111-22.

Margulis V, Shariat SF, Matin SF, et al. Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration. Cancer 2009; 115(6): 1224-33.

Babjuk M, Bohle A, Burger M, et al. EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. European urology 2017; 71(3): 447-61.

Li WM, Shen JT, Li CC, et al. Oncologic outcomes following three different approaches to the distal ureter and bladder cuff in nephroureterectomy for primary upper urinary tract urothelial carcinoma. European urology 2010; 57(6): 963-9.

Seisen T, Granger B, Colin P, et al. A Systematic Review and Meta-analysis of Clinicopathologic Factors Linked to Intravesical Recurrence After Radical Nephroureterectomy to Treat Upper Tract Urothelial Carcinoma. European urology 2015; 67(6): 1122-33.

Mathieu R, Bensalah K, Lucca I, Mbeutcha A, Roupret M, Shariat SF. Upper urinary tract disease: what we know today and unmet needs. Translational andrology and urology 2015; 4(3): 261-72.

Green DA, Rink M, Xylinas E, et al. Urothelial carcinoma of the bladder and the upper tract: disparate twins. The Journal of urology 2013; 189(4): 1214-21.

Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR. A simulation study of the number of events per variable in logistic regression analysis. Journal of clinical epidemiology 1996; 49(12): 1373-9.

Kiemeney LA, Witjes JA, Verbeek AL, Heijbroek RP, Debruyne FM. The clinical epidemiology of superficial bladder cancer. Dutch South-East Cooperative Urological Group. British journal of cancer 1993; 67(4): 806-12.

Wolf H, Hojgaard K. Urothelial dysplasia in random mucosal biopsies from patients with bladder tumours. Scandinavian journal of urology and nephrology 1980; 14(1): 37-41.

Wolf H, Hojgaard K. Urothelial dysplasia concomitant with bladder tumours as a determinant factor for future new occurrences. Lancet (London, England) 1983; 2(8342): 134-6.

Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 1953; 6(5): 963-8.

Sidransky D, Frost P, Von Eschenbach A, Oyasu R, Preisinger AC, Vogelstein B. Clonal origin of bladder cancer. The New England journal of medicine 1992; 326(11): 737-40.

Aben KK, Witjes JA, van Dijck JA, Schalken JA, Verbeek AL, Kiemeney LA. Lower incidence of urothelial cell carcinoma due to the concept of a clonal origin. European journal of cancer (Oxford, England : 1990) 2000; 36(18): 2385-9.

Weinstein JN AR, Broom BM, Wang W, et al. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 2014; 507(7492): 315-22.

Zhao YG, Shi BY, Qian YY, Bai HW, Xiao L, He XY. Dynamic expression changes between non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Tumori 2014; 100(6): e273-81.

Sfakianos JP, Cha EK, Iyer G, et al. Genomic Characterization of Upper Tract Urothelial Carcinoma. European urology 2015; 68(6): 970-7.

Moss TJ, Qi Y, Xi L, et al. Comprehensive Genomic Characterization of Upper Tract Urothelial Carcinoma. European urology 2017; 72(4): 641-9.

Cha EK, Shariat SF, Kormaksson M, et al. Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma. European urology 2012; 61(4): 818-25.

Cohen A, Kuchta K, Park S. Neoadjuvant and adjuvant chemotherapy use in upper tract urothelial carcinoma. Urologic oncology 2017; 35(6): 322-7.

Pearce SM, Pariser JJ, Patel SG, Steinberg GD, Shalhav AL, Smith ND. The effect of surgical approach on performance of lymphadenectomy and perioperative morbidity for radical nephroureterectomy. Urologic oncology 2016; 34(3): 121.e15-21.

Huang WW, Huang HY, Liao AC, et al. Primary urothelial carcinoma of the upper tract: important clinicopathological factors predicting bladder recurrence after surgical resection. Pathology international 2009; 59(9): 642-9.

Sanderson KM, Cai J, Miranda G, Skinner DG, Stein JP. Upper tract urothelial recurrence following radical cystectomy for transitional cell carcinoma of the bladder: an analysis of 1,069 patients with 10-year followup. The Journal of urology 2007; 177(6): 2088-94.

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

Park S, Hong B, Kim CS, Ahn H. The impact of tumor location on prognosis of transitional cell carcinoma of the upper urinary tract. The Journal of urology 2004; 171(2 Pt 1): 621-5.

Hall MC, Womack S, Sagalowsky AI, Carmody T, Erickstad MD, Roehrborn CG. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology 1998; 52(4): 594-601.

Raman JD, Ng CK, Scherr DS, et al. Impact of tumor location on prognosis for patients with upper tract urothelial carcinoma managed by radical nephroureterectomy. European urology 2010; 57(6): 1072-9.

Published
2018-12-13
How to Cite
Goldberg, H., Cheung, D. C., Chandrasekar, T., Klaassen, Z., Wallis, C. J., Kulkarni, G. S., Sayyid, R., Evans, A., Masoomian, M., Bapat, B., van der Kwast, T., Hamilton, R. J., Zlotta, A., & Fleshner, N. (2018). Are there differences between de novo and secondary upper tract urothelial carcinoma tumors?. Canadian Urological Association Journal, 13(9). https://doi.org/10.5489/cuaj.5595
Section
Original Research