Non–muscle invasive bladder cancer (Ta, T1, and CIS), describes malignant urothelial tumors that have not invaded the detrusor.
- Approximately 70% of malignant bladder tumors are non–muscle invasive at presentation. (70% present as stage Ta, 20% as T1, and 10% as CIS).
Signs and Symptoms Bladder Tumors
- The common symptoms of localized disease (hematuria, dysuria).
- Microscopic hematuria is associated with a 0.5% to 10.5% rate of bladder cancer.
- Patients with macroscopic (gross) hematuria have reported rates of bladder cancer of 13% to 34.5%.
- The presence of irritative voiding symptoms may double the risk, especially for CIS (5% vs. 10.5%).
- About 15% of patients are asymptomatic at presentation and are diagnosed when an incidental lesion is found on radiologic evaluation.
- Cystoscopy and upper tract imaging are indicated in patients with hematuria and/or unexplained irritative symptoms.
- Low-grade Ta lesions are low risk, whereas all high-grade lesions (including CIS) have a high risk of progressing.
- Patients may also present with symptoms of advanced disease, including flank or abdominal mass, weight loss, anorexia, and bone pain.
Consideration in the Diagnosis of Bladder Cancer
- Recurrence is common in all patients with non–muscle-invasive urothelial cancer but can often be controlled successfully with transurethral surgery, intravesical therapy, or a combination.
- In contrast to recurrence, patients can be divided into low or high risk for progression, which is the true concern.
- Low-grade Ta lesions are low risk, whereas all high-grade lesions (including CIS) have a high risk of progressing.
- Low-grade Ta lesions recur at a rate of 50% to 70% and progress in approximately 5% of cases.
- In contrast, high-grade T1 lesions recur in more than 80% of cases and progress in 50% of patients within 3 years.
- This behavior is primarily grade, rather than stage, dependent, because patients with high-grade tumors progressed with similar frequency regardless of whether they were invasive (T1) or noninvasive (Ta).
- Prognosis also correlates with tumor size, multiplicity, papillary versus sessile configuration, presence or absence of lymphovascular invasion, and status of the remaining urothelium.
- The variance in biologic behavior for low-grade versus high-grade lesions correlates with the known dual molecular lines of genetic development for these two pathways and supports the concept that high-grade and low-grade cancers may be considered as essentially different diseases.
- Chromosomal alterations caused by oxidative DNA damage create two separate genetic pathways to the development of UC.
- The first and more common (low grade) leads to noninvasive, papillary tumors.
- These usually follow an indolent course unless they convert to or are associated with a tumor of the second pathway.
- The second pathway leads to the development of high-grade cancer including CIS, T1, and, ultimately, muscle-invasive carcinoma.
- High-grade tumors tend to have numerous and greatly variable chromosomal gains and losses.
- In addition to their relatively predictable aneuploidy, high-grade tumors can also lose all or part of chromosome 9.
- Because of these differing genetic imprints, it has been suggested that papillary pTa tumors could almost be considered benign and might be a completely separate disease entity in contrast to high-grade tumors.
- High-grade and low-grade lesions are known to coexist.
- UC is traditionally considered a field change disease, with tumors arising at different times and sites.
- Rarely, patients who initially have low-grade tumors will subsequently develop high-grade tumor.
- Long-term surveillance is usually reasonable.
Detection of Urothelial Bladder Tumors
- Painless gross hematuria occurs in 85% of patients with bladder cancer and requires a complete evaluation that includes cystoscopy, urine cytology, CT scan, and a PSA blood test.
- Patients with microscopic hematuria require a full evaluation, but low-risk patients do not require repeat evaluations. High-risk individuals primarily are those with a smoking history and should be evaluated every 6 months.
- White light cystoscopy with random bladder biopsies is the gold standard for tumor detection.
- White light cystoscopy has an excellent sensitivity and specificity for papillary tumors but is relatively poor for CIS.
- Cystoscopy with blue light may be more sensitive in the detection of CIS.
- Porphyrin-induced fluorescence cystoscopy uses photoactive porphyrins, such as hexaminolevulinate, that accumulate preferentially in neoplastic tissue and emit red fluorescence under blue-wavelength light.
- This may improve the detection of small papillary lesions and CIS.
- There are various urine markers that evaluate secreted proteins or shed cells in the hope of noninvasively detecting bladder cancer.
- None of these markers to date have a high enough sensitivity or specificity to replace office cystoscopy.
- NMP-22 is commonly used along with cystoscopy in approximately 10% of patients.
References
- Epstein JI, Amin MB, Reuter VR, Mostofi FK: The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Bladder Consensus Conference Committee. Am J Surg Pathol 1998; 22:1435-1448.
- Golin AL, Howard RS: Asymptomatic microscopic hematuria. J Urol 1980; 124:389-391.
- Grossfeld GD, Wolf Jr JS, Litwan MS, et al: Asymptomatic microscopic hematuria in adults: summary of the AUA best practice policy recommendations. Am Fam Physician 2001; 63:1145-1154.
- Grossman HB, Soloway M, Messing E, et al: Surveillance for recurrent bladder cancer using a point-of-care proteomic assay. JAMA 2006; 295(3):299-305.
- Harnden P: A critical appraisal of the classification of urothelial tumours: time for a review of the evidence and a radical change?. BJU Int 2007; 99(4):723-725.
- Herr HW: Tumor progression and survival of patients with high grade, noninvasive papillary (TaG3) bladder tumors: 15-year outcome. J Urol 2000; 163:60-61.discussion 61–62.
- Herr HW, Donat SM: A comparison of white-light cystoscopy and narrow-band imaging cystoscopy to detect bladder tumour recurrences. BJU Int 2008; 102(9):1111-1114.
- Khadra MH, Pickard RS, Charlton M, et al: A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice. J Urol 2000; 163:524-527.
- Kiemeney LA, Witjes JA, Verbeek AL, et al: The clinical epidemiology of superficial bladder cancer. Dutch South-East Cooperative Urological Group. Br J Cancer 1993; 67:806-812.
- Kunju LP, You L, Zhang Y, et al: Lymphovascular invasion of urothelial cancer in matched transurethral bladder tumor resection and radical cystectomy specimens. J Urol 2008; 180(5):1928-1932.
- Lee LW, Davis Jr E: Gross urinary hemorrhage: a symptom, not a disease. JAMA 1953; 153:782-784.
- Lotan Y, Gupta A, Shariat SF, et al: Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy. J Clin Oncol 2005; 23:6533-6539.
- Mohr DN, Offord KP, Owen RA, et al: Asymptomatic microhematuria and urologic disease: a population-based study. JAMA 1986; 256:224-229.
- Murphy WM, Crabtree WN, Jukkola AF, Soloway MS: The diagnostic value of urine versus bladder washing in patients with bladder cancer. J Urol 1981; 126(3):320-322.
- Richter J, Jiang F, Gorog JP, et al: Marked genetic differences between stage pTa and stage pT1 papillary bladder cancer detected by comparative genomic hybridization. Cancer Res 1997; 57:2860-2864.
- Ro JY, Staerkel GA, Ayala AG: Cytologic and histologic features of superficial bladder cancer. Urol Clin North Am 1992; 19:435-453.
- Sauter G, Mihatsch MJ: Pussycats and baby tigers: non-invasive (pTa) and minimally invasive (pT1) bladder carcinomas are not the same!. J Pathol 1998; 185:339-341.
- Smith Jr JA, Labasky RF, Cockett AT, et al: Bladder cancer clinical guidelines panel summary report on the management of non–muscle-invasive bladder cancer (stages Ta, T1 and TIS). The American Urological Association. J Urol 1999; 162:1697-1701.
- Soloway MS, Briggman V, Carpinito GA, et al: Use of a new tumor marker, urinary NMP22, in the detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment. J Urol 1996; 156:363-367.
- Sultana SR, Goodman CM, Byrne DJ, et al: Microscopic hematuria: urological investigation using a standard protocol. Br J Urol 1996; 78:691-698.
- Tissot WD, Diokno AC, Peters KM: A referral center's experience with transitional cell carcinoma misdiagnosed as interstitial cystitis. J Urol 2004; 172:478-480.
- Varkarakis MJ, Gaeta J, Moore RH, et al: Superficial bladder tumor: aspects of clinical progression. Urology 1974; 4:414-420.