Upper and Lower Tract Urothelial Cancers: Relationship & Risks of Recurrence

Urothelial cancers refer to a cancer of the lining of the urinary system.  They can occur in the upper urinary tract (kidney and ureter) or the lower urinary tract (bladder, and prostate in men).  While cancers of the upper urinary tract (UTUC) have some similarities with bladder cancers, they can also have very different origins and clinical behavior patterns (click here to read the prior blog entry on UTUC).  For instance, urothelial cancer of the bladder is much more common, accounting for nearly 95% of all urothelial cancers.[1]  However, they do share certain characteristics and risk factors (i.e. smoking), therefore patients with bladder cancer are at risk for UTUC and patients with UTUC are at risk for subsequent bladder cancer.

In this blog we review the risks of subsequent urothelial cancer after a diagnosis of UTUC or bladder cancer.

UTUC after known Bladder Cancer

Considering that approximately 300,000 patients have bladder cancer each year in the US, it is estimated that only 2-4% of bladder cancer patients will develop UTUC.  However, the relative risk of developing UTUC is approximately 65-75% and highest in the first two years following a diagnosis of bladder cancer.  That relative risk decreases to 40-50% but remains stable for more than 10 years following an initial diagnosis.[2]

The risk of developing UTUC does vary with bladder cancer pathology and is highest in patients with:

• carcinoma in situ (CIS) of the bladder [3-5] 
• patients with CIS have a higher risk of UTUC than patients with non-invasive cancers 
• in patients undergoing radical cystectomy, patients with CIS have a higher risk of UTUC than patients with invasive cancers.
• these cancers are more likely to occur in the distal ureter
• recurrence is more likely if the patient was BCG-refractory
• high-grade tumors
• T1 versus Ta disease
• multifocal tumors
• the presence of ureteral reflux
• tumors located at the trigone or abutting the ureteral orifices [6,7] 

Bladder Cancer after UTUC

The risk of bladder cancer after UTUC is believed to be much higher than the risk of UTUC after bladder cancer, although the actual rates vary from 15-75% in a number of studies.[8-10]  The increased risk of bladder cancer is believed due to: (1) seeding of the bladder from upstream UTUC, (2) longer exposure of the bladder urothelium to carcinogens during urine storage, as opposed to the constant stream of urine through the upper tract; and (3) the larger number of urothelial cells (surface area) in the bladder.  Interestingly, while UTUC and bladder cancers often have different genetic and embryologic origins, bladder cancers that develop after UTUC will share specific genetic alterations with the primary UTUC supporting the theories above.[11,12]  

SUmmary

• UTUC and bladder cancer are related.
• It is more likely for bladder cancer to develop after UTUC than UTUC to develop after bladder cancer.
• For patients with bladder cancer, cis, grade, stage and tumor location(s) increase the risk of recurrence.
• Routine bladder surveillance (cystoscopy and cytology) is recommended for any patient with UTUC due to the high risk of recurrence in the bladder.

[1] Melamed MR, Reuter VE: Pathology and staging of urothelial tumors of the kidney and ureter. Urol Clin North Am 1993; 20: 333

[2] Rabbani F, Perrotti M, Russo P,et al: Upper-tract tumors after an initial diagnosis of bladder cancer: argument for long-term surveillance. J Clin Oncol 2001; 19: 94-100

[3] Solsona E, Iborra I, Ricos JV,et al: Upper urinary tract involvement in patients with bladder carcinoma in situ (CIS): its impact on management. Urology 1997; 49: 347-352
[4] Premoli J: Risk factors for upper tract recurrence in patients undergoing long-term surveillance for stage Ta bladder cancer. J Urol 2006; 175: 74-77
[5] Slaton JW, Swanson DA, Grossman HB,et al: A stage specific approach to tumor surveillance after radial cystectomy for transitional cell carcinoma of the bladder. J Urol 1999; 162: 710-714
[6] Wright JL, Hotaling J, Porter MP,et al: Predictors of upper tract urothelial cell carcinoma after primary bladder cancer: a population based analysis. J Urol 2009; 181: 1035-1039
[7] Zincke H, Garbeff PJ, Beahrs JR,et al: Upper urinary tract transitional cell cancer after radical cystectomy for bladder cancer. J Urol 1984; 131: 50-52
[8] Hisataki T, Miyao N, Masumori N,et al: Risk factors for the development of bladder cancer after upper tract urothelial cancer. Urology 2000; 55: 663-667
[9] Kang CH, Yu TJ, Hsieh HH,et al: The development of bladder tumors and contralateral upper urinary tract tumors after primary transitional cell carcinoma of the upper urinary tract. Cancer 2003; 98: 1620-1626
[10] Miyake H, Hara I, Arakawa S,et al: A clinical pathological study of bladder cancer associated with upper urinary tract cancer. BJU Int 2000; 85: 37
[11] Habuchi T, Takahashi R, Yamada H,et al: Metachronous multifocal development of urothelial cancers by intraluminal seeding. Lancet 1993; 342: 1087
[12] Takahashi T, Mitsumori K, Kakehi Y,et al: Distinct microsatellite alterations between upper urinary tract tumors and subsequent bladder tumors. J Urol 2000; 163: 549A