Clinical vignette: The case of a 76-year-old woman with increased urination frequency, dysuria, and malodorous urine is presented. No bacteria have been identified in two urine cultures performed. In any case, empirical treatment with antibiotics has improved the symptoms. After 3 months, the patient had an episode of hematuria for which she was referred to a specialist and was diagnosed with transitional bladder carcinoma. |
What are the types of bladder cancer?
In developed countries, 90% of carcinomas are transitional and the rest are squamous.
In endemic areas, 70% of cases are squamous cell carcinomas related to schistosomiasis.
20% of the tumors invaded the muscle at the time of diagnosis, indicating a poor prognosis.
Risk factors are: smoking, chronic infection, radiotherapy, and (before being regulated) industrial dyes.
Why is your diagnosis delayed?
Bladder cancer is more common in men and in women it takes a long time to diagnose. The English National Audit of Cancer Diagnosis in Primary Care (2009-10) estimated that 435 women experienced a longer delay in cancer diagnosis than men. There is little information in primary care services in England to explain the reasons for this delay.
There is no effective tool to detect it. In general, the diagnosis is symptomatic, with hematuria being the most common symptom present in both sexes in primary care (probability ratio 59.95%, confidence interval 51 to 57).
The odds ratio summarizes how many times patients with bladder cancer will have a certain finding relative to patients without cancer. A probability (ratio) less than 10 (or less than 0.1) is considered a strong evidence factor to confirm (or rule out) the diagnosis.
A recurring finding that appears in a study of outpatients with hematuria is the delay in diagnosis after its onset in women. This study was conducted with a sample of 7,649 individuals over 65 years of age in the USA (female/male ratio 1:2.43).
The average time to diagnosis was 85.5 days in women (95% confidence interval 81.3 to 89.4) compared with 73.6 days (71.2 to 76.1) in men (P<0.001). This difference seems to persist over time, women had a delay in diagnosis of 26% at 3 months after the consultation, 16% at 6 months and 23% at 9 months.
During the investigations, women underwent more urinalysis (1.39 vs. 1.19, P<0.001) and urine cultures (0.83 vs. 0.53, P<0.001) and had more positive results for urinary tract infections (odds ratio 2.32, 95% confidence interval 2.07 to 2.59; P<0.001) in addition, they received more antibiotics (40.1% v 35.4%P <0.001), and underwent fewer imaging studies (odds ratio 0.80 , 0.71 to 0.89, P<0.001).
Bladder cancer is also associated with voiding disorders and abdominal pain. Information from the primary care system and gynecology services in Europe indicates that women with these symptoms are frequently treated empirically without a correct clinical evaluation in 47% of cases, compared to 19% in men, in the year prior to diagnosis (P<0.05).
Although this information does not come entirely from the primary care system, it appears that prolonged investigation and treatment for urinary infections in repeated consultations (without resolution of symptoms) is a problem that occurs more frequently in women.
Why is this important?
Despite the recognized sex differences that influence tumor biology, bladder anatomy, and environmental and hormonal exposure that contribute to different outcomes, there is evidence of a correlate between delay in primary care and a worse prognosis.
How common is bladder cancer in women?
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Prospective data from the United Kingdom collected from 1537 cases of bladder cancer (1340 in detailed stage and 633 in detailed stage + cause of death) showed an association indicating that the longer the time between the onset of symptoms and referral to the specialist increases the incidence of bladder cancer with invasion of muscle tissue by 5% (p=0.04).
Survival at 5 years was less in those women who had muscle invasion at the time of diagnosis. (P<0.001).
This study did not distinguish between delay in consultation and delay in referral to a specialist, the longer delay before referring the patient (>14 vs <14 days) resulted in an increased risk of death and a 5% lower survival. at 5 years old. (P=0.02). Patients with delayed referral to a specialist appear to have more advanced disease, with worse outcomes.
How is it diagnosed?
Clinical:
NICE recommends urgent referral to a urologist in people over 40 years of age with hematuria in the absence of urinary tract infection or in the presence of recurrent or persistent urinary infections.
The same applies to patients over 50 years of age with microscopic hematuria of unknown cause and the presence of an abnormal mass in the bladder area. Referral is not urgent in patients under 50 years of age with unexplained microscopic hematuria without increased creatinine or proteinuria.
Most studies conducted in primary care settings examined cases of hematuria alone. Except for two of these studies that used previous medical records and reported a large number of symptoms associated with bladder cancer per se along with urinary tract cancer. Most patients presented with hematuria without pain, fictional symptoms, or a combination of both.
Hematuria:
A case-control study conducted in the United Kingdom using computerized medical records showed that painless macroscopic hematuria is the strongest predictor of bladder cancer in primary care (odds ratio 34, 95% confidence interval 29 to 41) with a positive predictive value in patients over 60 years of age of 3.9% (3.5% to 4.6%).
A nationwide evaluation showed that two-thirds of patients have hematuria as their first symptom in primary care. A prospective secondary care study revealed that 90% of referred patients had hematuria (its severity did not correlate with the severity of the disease), 25% of these referred patients will have transitional bladder carcinoma.
Few specific symptoms:
This case-control study also showed that frequently appear:
-Symptoms of dysuria (odds ratio 4.1m 95% confidence interval 3.4 to 5.0),
-Abdominal pain (2.0, 1.6 to 2.4)
-constipation (1.5 , 1.2 to 1.9) -
Diagnosed urinary tract infection (2.2, 2.0 to 2.5)
These symptoms are associated with a lower predictive value for cancer. Patients with advanced disease may present with pelvic pain or urinary tract obstruction. In some of these patients a mass can be palpated. Persistent symptoms and repeated visits are associated with a higher risk of cancer.
Carrying out non-specific studies
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Urinalysis is appropriate to detect hematuria, proteinuria, nitrites, leukocytes. It is also necessary to perform a urine culture to confirm infection.
Although 3 blood tests with abnormal results (elevated white blood cells, elevated inflammatory markers, and increased creatinine) are associated with this cancer, they alone cannot be used for diagnosis.
The main rule in urinary cytology is the follow-up of patients with carcinoma in situ.
Studies carried out in primary care have not reported on these procedures in diagnosis, their sensitivity is 38% in secondary care and probably lower in primary care.
Definitive diagnosis
Flexible cytology is the main study to confirm the diagnosis. It allows direct visualization and the possibility of biopsying abnormalities of the bladder tissue. It is not useful for treatment.
In case of overlapping kidney and bladder symptoms, ultrasound is used.
To stage patients with bladder cancer, a computed tomography and isotope bone scan should be performed. Positron emission tomography is increasingly used in specialized centers.
How is it treated?
Initial treatment depends on the stage.
If the disease is not very advanced, it can be resected transurethral. Patients with low-risk disease can be followed with surveillance cystoscopy.
Recurrent low-risk or intermediate/high-risk disease may require chemotherapy or immunotherapy.
More advanced stages may require cystectomy, radical radiotherapy with or without neo-adjuvant chemotherapy.
Key points
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