Bladder Cancer
Bladder cancer is usually transitional cell
(urothelial) carcinoma. Patients usually present with hematuria (most commonly)
or irritative voiding symptoms such as frequency and/or urgency; later, urinary
obstruction can cause pain. Diagnosis is by cystoscopy and biopsy. Treatment is
with fulguration, transurethral resection, intravesical instillations, radical
surgery, chemotherapy, external beam radiation, or a combination.- (see also urinary tract infections)
Risk factors include the following:
·
Smoking (the most common risk
factor, causing ≥ 50% of new cases)
·
Excess phenacetin use
(analgesic abuse)
·
Long-term cyclophosphamide use
·
Chronic irritation (eg, in
schistosomiasis, by chronic catheterization, or by bladder calculi)
·
Exposure to hydrocarbons,
tryptophan metabolites, or industrial chemicals, notably aromatic amines
(aniline dyes, such as naphthylamine used in the dye industry) and chemicals
used in the rubber, electric, cable, paint, and textile industries
Types of bladder cancer include
Transitional
cell carcinomas (urothelial carcinoma), which
account for > 90% of bladder cancers. Most are papillary carcinomas, which
tend to be superficial and well-differentiated and to grow outward; sessile
tumors are more insidious, tending to invade early and metastasize.
Squamous
cell carcinomas, which are less common and usually
occur in patients with parasitic bladder infestation or chronic mucosal
irritation.
Adenocarcinomas, which may occur as primary tumors or rarely reflect metastasis
from intestinal carcinoma. Metastasis should be ruled out.
In > 40% of patients, tumors recur at
the same or another site in the bladder, particularly if tumors are large or
poorly differentiated or if several tumors are present. Bladder cancer tends to
metastasize to the lymph nodes, lungs, liver, and bone. Expression of mutations
in tumor gene p53 may be associated with both progression and resistance to chemotherapy.
In the bladder, carcinoma in situ is high
grade but noninvasive and usually multifocal; it tends to recur.
Symptoms and Signs of Bladder Cancer
Most patients present with unexplained
hematuria (gross or microscopic). Some patients present with anemia, and
hematuria is detected during evaluation. Irritative voiding symptoms ( dysuria,
burning, frequency) and pyuria are also common at presentation. Pelvic pain
occurs with advanced cancer, when a pelvic mass may be palpable.
Diagnosis of Bladder Cancer
Cystoscopy with biopsy
Urine cytology
Bladder cancer is suspected clinically. If
patients present with hematuria, workup is risk-stratified and involves a
combination of diagnostic cystoscopy and imaging (CT urogram or renal
ultrasound [ 1]). Urine cytology, which can detect malignant cells, should also
be done. Cystoscopy and biopsy of abnormal areas or resection of tumors are
required for diagnosis and clinical staging. Urinary antigen tests are
available but are not routinely recommended for use in diagnosis. They are used
sometimes if cancer is suspected but cytology results are negative.
Cystoscopy with blue light after
intravesical instillation of hexyl-aminolevulinate can improve initial
detection of bladder cancer as well as recurrence-free survival. Higher
detection rates are expected to improve clinical outcomes by reducing future
recurrences and by facilitating earlier recognition that certain tumors are
unresponsive to therapy (thus, sparing some patients unnecessary treatments).
Metastatic and recurrent cancers
Metastases require chemotherapy, generally
cisplatin based, which is frequently effective but rarely curative unless
metastases are confined to lymph nodes. This can be followed by maintenance
immunotherapy with avelumab. Combination chemotherapy may prolong life in
patients with metastatic disease. For patients who are cisplatin ineligible or
have progressed after receiving cisplatin-based regimens, newer immunotherapies
using PD-1 and PD-L1 inhibitors are available, such as pembrolizumab and
atezolizumab. The first targeted therapy, erdafitinib, is now available for use
in patients with FGFR3 and FGFR2 mutations who have failed treatment with
chemotherapy.
Treatment of recurrent cancer depends on clinical
stage and site of recurrence and previous treatment. Recurrence after
transurethral resection of superficial tumors is usually treated with a 2nd
resection or fulguration. Early cystectomy is recommended for recurrent
high-grade superficial bladder cancers.
Key Points
Risk of bladder cancer increases with
smoking, phenacetin or cyclophosphamide use, chronic irritation, or exposure to
certain chemicals.
Transitional (urothelial) cell carcinoma is
> 90% of bladder cancers.
Suspect bladder cancer in patients with
unexplained hematuria or other urinary symptoms (particularly in middle-aged or
older men).
Diagnose bladder cancer via cystoscopic
biopsy and, if there is muscle invasion, do imaging studies for staging.
Remove superficial cancers by transurethral
resection or fulguration, followed by repeated bladder instillations of drugs.
If cancer penetrates the muscle, treat with
neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy with
urinary diversion or, less frequently, radiation plus chemotherapy.