Differentials
Benign prostatic hyperplasia (BPH)
SIGNS / SYMPTOMS
Can cause hematuria and occurs in the same age and sex group as bladder cancer.
BPH is associated with reduced force of stream, frequency, urgency, and nocturia, as well as enlargement of the prostate on digital rectal exam. However, BPH is so common that these signs and symptoms provide essentially no aid in clinical differentiation.
INVESTIGATIONS
Urine cytology should be normal with BPH, but it is also often normal with low-grade bladder tumors.
Cystoscopy with biopsy of suspicious lesions: BPH and low-grade tumors are visible; carcinoma in situ and high-grade solid tumors, which may not be visible, should have positive cytology.
Imaging studies may show an inferior bladder mass.
Hemorrhagic cystitis
SIGNS / SYMPTOMS
Acute onset of severe frequency and dysuria in a young woman, particularly if associated with low back pain and malaise, suggests hemorrhagic cystitis. However, it can be difficult to distinguish from bladder cancer by clinical features alone.
INVESTIGATIONS
Resolution of hematuria is not an indication of benign disease. Cystoscopy is indicated for hematuria in the absence of a bacterial source, even when cytology is normal.
Prostatitis
SIGNS / SYMPTOMS
Typically occurs in men <55 years old. Prostatitis tends to be more relenting than malignant causes of dysuria and pelvic pain.
INVESTIGATIONS
Cytology is key to differentiating prostatitis and carcinoma of the bladder or prostate.
Cystoscopy and biopsy may also be required.
Urinary tract infection (UTI)
SIGNS / SYMPTOMS
Repeated UTI is a risk factor for bladder cancer. Symptoms of urgency, frequency, dysuria, and hematuria are shared by both UTI and bladder cancer and do not aid clinical differentiation. Back pain, fever, and chills are common with UTI, but rare with bladder cancer.
INVESTIGATIONS
Positive urine culture makes bladder cancer less likely, but does not exclude the diagnosis.
Nephrolithiasis
SIGNS / SYMPTOMS
A common cause of gross and microscopic hematuria, nephrolithiasis can be distinguished by typical symptoms of renal colic when present.
INVESTIGATIONS
Noncontrast CT scan will demonstrate stones, even uric acid stones. A plain x-ray can be diagnostic for radiopaque stones.
Inflammation from chronic foreign bodies and stones promotes urothelial carcinoma (UC); bladder and upper tract tumors may calcify, but imaging typically reveals the associated mass.
Renal cell carcinoma
SIGNS / SYMPTOMS
Ureteral casts can cause vermiform clots to signify upper tract hemorrhage. Bladder symptoms are infrequent. Rarely a renal mass may be palpable. Flank pain is uncommon, but may occur with clot obstruction, bleeding into the mass, or infiltration of perirenal structures.
INVESTIGATIONS
Abdominal and pelvic CT scan with and without contrast will typically identify renal cell carcinoma. Anemia and elevated sedimentation rate are common, and abnormal liver function tests, even in the absence of metastasis, occur not infrequently.
Upper tract urothelial carcinoma
SIGNS / SYMPTOMS
Renal pelvic and ureteral urothelial carcinomas have etiology and symptoms similar to urothelial carcinoma of the bladder: hematuria, and, much less frequently, dysuria. Flank pain, due to a clot or tumor tissue obstruction, occurs in up to a third of cases.[76]
Vermiform clots indicate upper tract bleeding.
INVESTIGATIONS
Cystoscopy and cross-sectional imaging of the upper tract with contrast including delayed images of the collecting system and ureter followed by ureteroscopy, and bladder and upper tract cytologic washing and biopsy can differentiate the site of malignancy.[77]
Gynecologic cancer or other pelvic cancers
SIGNS / SYMPTOMS
Symptoms of pelvic pain and mass are rare with bladder cancer, and somewhat more common with other tumors. Pelvic exam may reveal cervical, uterine, or pelvic mass in women. Digital rectal exam may detect rectal carcinoma or, in men, prostatic induration suggestive of prostate cancer.
INVESTIGATIONS
CT scan and, if needed, cystoscopy with cytology and biopsy can differentiate these cancers.
Radiation cystitis
SIGNS / SYMPTOMS
Signs and symptoms indistinguishable from bladder cancer. Requires history of radiation exposure.
INVESTIGATIONS
Cystoscopy shows increased vascularity with irregular, tortuous vessels and inflammation. Biopsy and cytology, sometimes repeated, are required to differentiate.
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