Differentials

Benign prostatic hyperplasia (BPH)

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SIGNS / SYMPTOMS

Can cause haematuria 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 examination. However, BPH is so common that these signs and symptoms provide essentially no aid in clinical differentiation.

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Urine cytology should be normal with BPH, but it is also often normal with low-grade bladder tumours.

Cystoscopy with biopsy of suspicious lesions: BPH and low-grade tumours are visible; carcinoma in situ and high-grade solid tumours, which may not be visible, should have positive cytology.

Imaging studies may show an inferior bladder mass.

Haemorrhagic cystitis

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Acute onset of severe frequency and dysuria in a young woman, particularly if associated with low back pain and malaise, suggests haemorrhagic cystitis. However, it can be difficult to distinguish from bladder cancer by clinical features alone.

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Resolution of haematuria is not an indication of benign disease. Cystoscopy is indicated for haematuria in the absence of a bacterial source, even when cytology is normal.

Prostatitis

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Typically occurs in men <55 years old. Prostatitis tends to be more relenting than malignant causes of dysuria and pelvic pain.

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Cytology is key to differentiating prostatitis and carcinoma of the bladder or prostate.

Cystoscopy and biopsy may also be required.

Urinary tract infection (UTI)

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Repeated UTI is a risk factor for bladder cancer. Symptoms of urgency, frequency, dysuria, and haematuria 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.

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Positive urine culture makes bladder cancer less likely, but does not exclude the diagnosis.

Nephrolithiasis

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A common cause of gross and microscopic haematuria, nephrolithiasis can be distinguished by typical symptoms of renal colic when present.

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Non-contrast 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 tumours may calcify, but imaging typically reveals the associated mass.

Renal cell carcinoma

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Ureteral casts can cause vermiform clots to signify upper tract haemorrhage. 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.

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Abdominal and pelvic CT scan with and without contrast will typically identify renal cell carcinoma. Anaemia and elevated sedimentation rate are common, and abnormal liver function tests, even in the absence of metastasis, occur not infrequently.

Upper tract urothelial carcinoma

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Renal pelvic and ureteral urothelial carcinomas have aetiology and symptoms similar to urothelial carcinoma of the bladder: haematuria and, much less frequently, dysuria. Flank pain, due to a clot or tumour tissue obstruction, occurs in up to a third of cases.[77]

Vermiform clots indicate upper tract bleeding.

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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.[78] 

Gynaecological cancer or other pelvic cancers

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Symptoms of pelvic pain and mass are rare with bladder cancer, and somewhat more common with other tumours. Pelvic examination may reveal cervical, uterine, or pelvic mass in women. Digital rectal examination may detect rectal carcinoma or, in men, prostatic induration suggestive of prostate cancer.

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CT scan and, if needed, cystoscopy with cytology and biopsy can differentiate these cancers.

Radiation cystitis

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Signs and symptoms indistinguishable from bladder cancer. Requires history of radiation exposure.

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Cystoscopy shows increased vascularity with irregular, tortuous vessels and inflammation. Biopsy and cytology, sometimes repeated, are required to differentiate.

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