Impact of Histological Variants on Clinical Outcomes of Patients with Upper Urinary Tract Urothelial Carcinoma
We investigated the clinical and prognostic impact of variant histologies on upper tract urothelial carcinoma outcomes after radical nephroureterectomy.
Materials and Methods:
Data on 1,648 patients with upper tract urothelial carcinoma treated with radical nephroureterectomy without preoperative chemotherapy or radiotherapy were reviewed for histological differentiation and variants. We analyzed differences between pure upper tract urothelial carcinoma and upper tract urothelial carcinoma with variant histology, and differences in the histological variants using different stratifications.
A total of 398 patients (24.2%) had histological upper tract urothelial carcinoma variants. The most common variants were squamous cell and glandular differentiation in 9.9% and 4.4% of cases, respectively. Histological variants were associated with advanced tumor stage, tumor multifocality, sessile tumor architecture, tumor necrosis, lymphovascular invasion and lymph node metastasis compared to pure upper tract urothelial carcinoma (p ≤0.031). On univariable analysis variant histology was associated with disease recurrence (p = 0.002) and cancer specific mortality (p = 0.003). In 174 patients treated with adjuvant chemotherapy there was no difference in disease recurrence or survival between variant histology and pure upper tract urothelial carcinoma (p = 0.42 and 0.59, respectively). On multivariable analysis adjusted for the effects of standard clinicopathological characteristics variant histology was not associated with either end point.
Almost 25% of patients with upper tract urothelial carcinoma treated with radical nephroureterectomy harbored histological variants. Variant histology was associated with features of biologically aggressive upper tract urothelial carcinoma. While variant histology is associated with worse outcomes on univariable analysis but this effect did not remain significant on multivariable analysis.
- 1 : Prognostic factors for upper urinary tract urothelial carcinoma. Nat Rev Urol2011; 8: 440. Google Scholar
- 2 : Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin2011; 61: 212. Google Scholar
- 3 : Upper urinary tract tumors with nontransitional histology: a single-center experience. Urology2006; 67: 518. Google Scholar
- 4 : High-grade urothelial carcinoma of the renal pelvis: clinicopathologic study of 108 cases with emphasis on unusual morphologic variants. Mod Pathol2006; 19: 494. Google Scholar
- 5 : The impact of variant histology on the outcome of bladder cancer treated with curative intent. Urol Oncol2009; 27: 3. Google Scholar
- 6 : Comparative outcomes of pure squamous cell carcinoma and urothelial carcinoma with squamous differentiation in patients treated with radical cystectomy. J Urol2012; 187: 74. Link, Google Scholar
- 7 : Variant forms of bladder cancer: basic considerations on treatment approaches. Curr Oncol Rep2011; 13: 216. Google Scholar
- 8 : Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder. J Urol2006; 175: 2048. Link, Google Scholar
- 9 : Reply from authors re: Mark S. Soloway, Michael Garcia-Roig, Michael A. Gorin and Rajinikanth Ayyathurai: How can we improve outcomes for upper tract urothelial carcinoma?. Eur Urol2012; 61: 254. Google Scholar
- 10 : Squamous cell carcinoma of the renal pelvis and ureter: incidence, symptoms, treatment and outcome. J Urol2007; 178: 51. Link, Google Scholar
- 11 : The impact of tumor multifocality on outcomes in patients treated with radical nephroureterectomy. Eur Urol2012; 61: 245. Google Scholar
- 12 : AJCC Staging Manual. New York: Springer2010. Google Scholar
- 13 : Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs: World Health Organization Classification of Tumours. Lyon: IARCC Press2004. Google Scholar
- 14 : Tumour architecture is an independent predictor of outcomes after nephroureterectomy: a multi-institutional analysis of 1363 patients. BJU Int2009; 103: 307. Google Scholar
- 15 : Lymphovascular invasion predicts clinical outcomes in patients with node-negative upper tract urothelial carcinoma. J Clin Oncol2009; 27: 612. Google Scholar
- 16 : Prognostic role of lymphovascular invasion in patients with urothelial carcinoma of the upper urinary tract: an international validation study. Eur Urol2010; 57: 1064. Google Scholar
- 17 : Tumour necrosis is an indicator of aggressive biology in patients with urothelial carcinoma of the upper urinary tract. Eur Urol2010; 57: 575. Google Scholar
- 18 : Stage-specific impact of tumor location on oncologic outcomes in patients with upper and lower tract urothelial carcinoma following radical surgery. Eur UrolFebruary 15, 2012; . Epub ahead of print. Google Scholar
- 19 : Death certificates are valid for the determination of cause of death in patients with upper and lower tract urothelial carcinoma. Eur Urol2012; 61: 854. Google Scholar
- 20 : Micropapillary carcinoma of the renal pelvis and ureter. J Urol2006; 175: 463. Link, Google Scholar
- 21 : Micropapillary urothelial carcinoma of the upper urinary tract: clinicopathologic study of five cases. Am J Clin Pathol2006; 126: 86. Google Scholar
- 22 : Sarcomatoid carcinoma of the upper urinary tract: clinical outcome and molecular characterization. Hum Pathol2009; 40: 211. Google Scholar
- 23 : 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 Int2011; 108: 693. Google Scholar
- 24 : Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma. Cancer2010; 116: 3127. Google Scholar
- 25 : Changes in renal function following nephroureterectomy may affect the use of perioperative chemotherapy. Eur Urol2010; 58: 581. Google Scholar