In developed countries, 90% of bladder cancers are metastatic cell carcinomas and the remainder are basically squamous carcinomas. In areas where schistosomiasis is endemic, squamous bladder cancer can account for 70% of cases. Twenty percent of bladder cancers are muscle-infiltrating lesions, and this often predicts a worse prognosis. The main risk factor for bladder cancer is smoking, but chronic infections, radiation and industrial dyes are also associated with its development.
Why is there a delay in diagnosis?
Because bladder cancer is more common in men, women are more likely to be delayed in their diagnosis. In the UK, oncology diagnosis data from 2009 to 2010 showed that 435 more women than men were delayed in diagnosis that year, but there is no data to explain why.
In the absence of a validated screening tool, diagnosis of bladder cancer is often made initially by clinical symptoms, such as hematuria (likelihood ratio 59.95% with a confidence interval of 51-57).
The likelihood ratio is the ratio of the probability of a screening test result in those with disease to the probability in those without disease, with a value greater than 10 (less than 0.1) meaning that the symptom confirms (excludes) the diagnosis of bladder cancer.
An outpatient data from the United States supports this conclusion: of the 7649 patients over 65 years of age presenting with hematuria (male to female ratio 2.43:1), women tended to be more likely to have a delayed diagnosis.
The average time to diagnosis was 85.5 days for women compared to 73.6 days for men. This difference persisted, with 26% of women delaying diagnosis by 3 months; 16% by 6 months; and 23% by 9 months.
Compared to men, women had more routine urine tests (1.39:1.19), urine cultures (0.83:0.53), were more often diagnosed with urinary tract infections and treated with antibiotics (40.1%:35.4%), and less often underwent cystography during the diagnosis process.
Clinical manifestations of bladder cancer also include urinary disturbances and abdominal pain. However, data from Europe in 2013 showed that women were more likely to be treated empirically without further diagnosis when they presented to the hospital with this complaint (women: men 47%: 19%). This means that it is more difficult for women to be diagnosed through repeated consultations over time with constant testing and treatment of urinary tract infections.
Why is this important?
While differences in tumor biology such as gender, bladder anatomy, environment, and hormone exposure are strongly associated with prognosis, there is also evidence that timely diagnosis is closely related to prognosis.
A prospective study of 1537 bladder cancers from the UK showed that delayed diagnosis after presentation of associated symptoms or at GP referral increased the incidence of muscle-infiltrating carcinoma by 5% (staging pT2-4).
A significant decrease in five-year survival was observed in women after the presentation of myxoid invasive carcinoma. Although the report did not distinguish between patient delays and GP delays, prolonged delays (less than 14 days: more than 14 days) would result in a higher risk of death and lower five-year survival rates. Delays caused by patients in the referral process lead to more disease progression and a worse prognosis.
How is it diagnosed?
1. Clinical features
The UK National Postgraduate Health Service (NPS) strongly recommends referral to a urologist as soon as possible for people who do not have a urinary tract infection but have carnal haematuria; who are older than 40 years with recurrent or persistent urinary tract infections; who are older than 50 years with unexplained microscopic haematuria; who are found to have an abdominal mass of bladder origin; and who are younger than 50 years with unexplained microscopic haematuria without elevated creatinine or urine protein (excluding nephritis).
Most primary care hospitals have now begun to focus on hematuria, although there are other clinical signs associated with bladder and urethral cancers based on past medical records. Most patients with bladder cancer present with simple painless hematuria or hematuria in combination with other clinical symptoms.
1.1 Hematuria
A case-control study in the UK showed that painless carnal haematuria in primary care was the strongest predictor of bladder cancer. National Audit Office data show that 2/3 of patients present to primary care with haematuria as their chief complaint, although secondary care data show that 90% of patients actually referred have haematuria (the degree of haematuria does not correlate with disease severity) and 25% of these are eventually found to have migratory cell carcinoma of the bladder.
1.2 Other specific symptoms
The case-control study described above also showed that some symptoms such as painful urination, abdominal pain, and constipation, and urinary tract infections are also associated with bladder cancer, but their predictive value is much lower than that of hematuria.
Patients with progressive bladder cancer often present with pelvic pain or urethral obstruction, but these patients usually have a visible abdominal mass. Importantly, persistent recurrence of these symptoms can increase the risk of tumor.
2.Tests and laboratory tests
2.1 Laboratory tests
Urinalysis can accurately detect hematuria, proteinuria, nitrite or leukocyte esterase values, followed by microscopy and culture to clarify the infection. Although elevated leukocytes, CRP and creatinine are associated with bladder cancer, one of these alone cannot be used as a basis for diagnosis of bladder cancer. Urine cytology is mainly used for follow-up of patients with carcinoma in situ and not for tumor diagnosis. No effective test for bladder cancer has been reported in primary care hospitals, but given that the sensitivity of the test in secondary care hospitals is only 38%, it is certainly even lower in primary care hospitals.
2.2 Tests
Cystoscopy is currently the predominant modality for the diagnosis of bladder cancer. It allows the physician to visualize the inside of the bladder and remove tissue for biopsy. However, it is not yet possible to use cystoscopy for treatment.
It is difficult to determine bladder and kidney cancer with color Doppler ultrasound of the renal tract. Staging of patients with bladder cancer can be done with CT and ECT and, in addition, Pet-CT is increasingly being used in the clinic.
How is it treated?
Initial treatment depends on the stage of the disease. Early stage tumors are often treated with transurethral resection of the bladder tumor. If the stage is early, routine cystoscopic review is sufficient; if there is a risk of recurrence or poor tumor type, bladder chemotherapy or immunotherapy will be required. For intermediate to advanced bladder cancer, neoadjuvant chemotherapy followed by cystectomy or radical radiotherapy may be indicated depending on the circumstances.
Summary
1. Women with bladder cancer are more likely to have muscle-infiltrating cancer, partly due to delayed diagnosis.
2.Hematuria is the most highly predictive factor of bladder cancer, and patients with hematuria should be promptly examined and referred.
3.If a female patient is judged to have a urinary tract infection, it must be confirmed that all her clinical symptoms have been completely resolved after the use of antibiotics.
4. Elderly women over 50 years old with clinical symptoms such as hematuria, if the infection cannot be confirmed by urinalysis, microscopy and culture, further tests are needed to clarify the diagnosis.