Noninvasive Bladder Cancer: Diagnosis and Management

Urothelial carcinoma does not have a strong inherited disease association. It is felt, however, that there are 2 separate molecular pathways that may lead to the development of bladder cancer [14]. Mutation of the p53 gene has been shown to be associated with carcinoma in situ and invasive disease, whereas mutation of FGFR3 is seen more frequently with Ta disease [15]. Accumulation of p53 in cell nuclei is an independent predictor of tumor recurrence and overall poor prognosis [16]. The identification of molecular markers of tumor progression is an active field of research in bladder cancer [17].

Case Patient 1

Initial Presentation and Evaluation

A 63-year-old man with a 60 pack-year history of smoking presents to a urologist with a urinalysis from his primary care physician showing 20 to 50 red blood cells per high-power field (RBCs/HPF). He denies any urgency, frequency, or recent urinary tract infections. A urine culture from his primary care doctor is negative.

• What are the common presenting features of bladder cancer?

Hematuria is the most common presenting feature of bladder cancer. It is present as the initial symptom in up to 90% of patients with urothelial carcinoma [18]. Other symptoms include irritative voiding symptoms such as urgency, frequency, and dysuria. Irritative voiding symptoms tend to occur more commonly with carcinoma in situ [19].

• What are the next steps in the workup of this patient?

Initial Evaluation

American Urological Association (AUA) guidelines for the evaluation and management of asymptomatic microhematuria were updated in 2011 [20]. They recommend that every patient who presents with microscopic hematuria (> 3 RBCs/HPF) undergo a thorough history and physical exam, including rectal exam and bimanual evaluation in females to assess for any masses or pelvic fixation. Once benign sources of hematuria (eg, infection, menstruation, vigorous exercise, medical renal disease, viral illness, trauma, or recent urological procedures) have been ruled out, further testing will include a renal function panel, upper tract imaging, as well as cystoscopy in high-risk patients and those older than age 35 years. Urine cytology may be utilized in high-risk patients, but it is no longer generally recommended for routine workup.

Imaging

The imaging modality of choice during the hematuria workup is the computed tomography urogram (CTU), a multiphasic CT scan that images the urinary tract before and after contrast administration and includes excretory stage imaging [21]. Sadow et al found that CTU had a negative predictive value (NPV) of 95% for the detection of bladder cancer, while cystoscopy had an NPV of 99% [22]. In addition to radiographic evaluation of the urinary system, CT offers useful staging information regarding metastatic disease. In patients with renal failure or other contraindications to CTU, magnetic resonance urography (MRU) has become an acceptable alternative for hematuria evaluation. MRU allows for improved characterization of tissue and does not utilize ionizing radiation. During MRU, the high T2 signal intensity of urine is utilized to provide contrast in the images in static phase MRU and after gadolinium administration for excretory-phase MRU [21]. The bladder is typically best evaluated in T1-weighted images a few minutes after gadolinium administration, before the contrast reaches the bladder; it may also be evaluated during the late excretory phase when signal enhancement from gadolinium is greatest. The effectiveness of MRU in collecting system evaluation is still evolving, and therefore, in appropriately selected patients who would benefit from further collecting system evaluation, MRU should be utilized in conjunction with retrograde pyelograms [20]. Though previously considered the gold standard in imaging, intravenous pyelography is no longer a recommended imaging modality for hematuria evaluation.