Current Perspectives in Bladder Cancer Management
Current Perspectives in Bladder Cancer Management
Numerous risk factors for TCC have been identified. Smoking is implicated in approximately two-thirds of bladder cancers in men and up to one-third in women. There is a fourfold increased incidence in current smokers relative to never-smokers, and bladder cancer risk is correlated with the number of cigarettes smoked, duration of smoking and age at smoking initiation. Those who stop smoking reduce their bladder cancer risk by 10–40% within 4 years, although former smokers retain a twofold higher incidence than never-smokers.
Data from Western Europe suggest that around 4–7% of bladder cancers in men are attributable to a known occupational carcinogen; the latent period between exposure and the development of cancer is about 20 years. Exposure to aniline dyes, aromatic amines (used in the manufacture of textiles, paints, plastics and rubber industries) and polycyclic aromatic amines are the primary toxins. Continuous arsenic exposure and ingestion has been reported to increase the risk of bladder cancer by as much as one thousand times.
Carcinogen-metabolising enzymes are in part controlled by genetic polymorphism. Slow acetylation of N-acetyltransferase-2, rapid cytochrome P1A2 activity and glutathione S-transferase M1 null genotype are associated with an increased risk of TCC. Approximately 20% of Europeans affected by bladder cancer are homozygous for a non-coding single nucleotide polymorphism (8q24.21) located close to the c-Myc oncogene.
Older studies have shown that pelvic radiotherapy for cervical cancer was associated with a twofold to fourfold increased risk of secondary bladder cancer. However, with contemporary radiotherapy, this risk has been reduced to a minimal level. In men with prostate cancer who received external beam radiotherapy and/or brachytherapy between 1973 and 1999, at 5 years, after the initial diagnosis of the primary cancer, 1–1.5% had developed a secondary bladder malignancy. However, it is estimated that with modern radiotherapy techniques, men with prostate cancer now have < 1% risk of a secondary malignancy.
It has been reported that treatment with cyclophosphamide for primary malignancies and autoimmune disease increases the risk of bladder cancer by fourfold to ninefold, and is higher with greater cumulative doses and longer duration of exposure. Mesna (2-mercaptoethanesulfonic acid) is commonly co-administered with cyclophosphamide to decrease the development of cyclophosphamide-induced bladder cancer. It is speculated that Mesna, which is almost exclusively excreted by the kidneys counteracts the toxic effects of acrolein, an inactive metabolite of cyclophosphamide. Historically, it has been reported that chronic abusers of the analgesic phenacetin had a four times higher risk of bladder malignancy relative to non-users. The major metabolite of phenacetin is acetaminophen (paracetamol), which is often present in modern analgesics. However, heavy use of acetaminophen-containing analgesics did not increase bladder cancer risk in a number of studies.
The oral antidiabetic drug pioglitazone is currently under post marketing pharmacovigilance, as a small excess of bladder cancer cases was shown in two studies evaluating its role in the management of diabetes. The risk was associated with drug exposure in excess of 2 years. However, the benefits of pioglitazone are considered to outweigh this small risk for those who respond to treatment and in whom there is no history or other risk of bladder cancer. As a general principle, people with diabetes and non-visible haematuria (NVH) should be considered for further investigation in the same way as any other individuals with NVH.
There are also reported associations between increased risk of urothelial cancers and Aristolochia fangchi (a Chinese herb found in some over-the-counter diet pills).
Risk Factors for Bladder Cancer
Numerous risk factors for TCC have been identified. Smoking is implicated in approximately two-thirds of bladder cancers in men and up to one-third in women. There is a fourfold increased incidence in current smokers relative to never-smokers, and bladder cancer risk is correlated with the number of cigarettes smoked, duration of smoking and age at smoking initiation. Those who stop smoking reduce their bladder cancer risk by 10–40% within 4 years, although former smokers retain a twofold higher incidence than never-smokers.
Data from Western Europe suggest that around 4–7% of bladder cancers in men are attributable to a known occupational carcinogen; the latent period between exposure and the development of cancer is about 20 years. Exposure to aniline dyes, aromatic amines (used in the manufacture of textiles, paints, plastics and rubber industries) and polycyclic aromatic amines are the primary toxins. Continuous arsenic exposure and ingestion has been reported to increase the risk of bladder cancer by as much as one thousand times.
Carcinogen-metabolising enzymes are in part controlled by genetic polymorphism. Slow acetylation of N-acetyltransferase-2, rapid cytochrome P1A2 activity and glutathione S-transferase M1 null genotype are associated with an increased risk of TCC. Approximately 20% of Europeans affected by bladder cancer are homozygous for a non-coding single nucleotide polymorphism (8q24.21) located close to the c-Myc oncogene.
Older studies have shown that pelvic radiotherapy for cervical cancer was associated with a twofold to fourfold increased risk of secondary bladder cancer. However, with contemporary radiotherapy, this risk has been reduced to a minimal level. In men with prostate cancer who received external beam radiotherapy and/or brachytherapy between 1973 and 1999, at 5 years, after the initial diagnosis of the primary cancer, 1–1.5% had developed a secondary bladder malignancy. However, it is estimated that with modern radiotherapy techniques, men with prostate cancer now have < 1% risk of a secondary malignancy.
It has been reported that treatment with cyclophosphamide for primary malignancies and autoimmune disease increases the risk of bladder cancer by fourfold to ninefold, and is higher with greater cumulative doses and longer duration of exposure. Mesna (2-mercaptoethanesulfonic acid) is commonly co-administered with cyclophosphamide to decrease the development of cyclophosphamide-induced bladder cancer. It is speculated that Mesna, which is almost exclusively excreted by the kidneys counteracts the toxic effects of acrolein, an inactive metabolite of cyclophosphamide. Historically, it has been reported that chronic abusers of the analgesic phenacetin had a four times higher risk of bladder malignancy relative to non-users. The major metabolite of phenacetin is acetaminophen (paracetamol), which is often present in modern analgesics. However, heavy use of acetaminophen-containing analgesics did not increase bladder cancer risk in a number of studies.
The oral antidiabetic drug pioglitazone is currently under post marketing pharmacovigilance, as a small excess of bladder cancer cases was shown in two studies evaluating its role in the management of diabetes. The risk was associated with drug exposure in excess of 2 years. However, the benefits of pioglitazone are considered to outweigh this small risk for those who respond to treatment and in whom there is no history or other risk of bladder cancer. As a general principle, people with diabetes and non-visible haematuria (NVH) should be considered for further investigation in the same way as any other individuals with NVH.
There are also reported associations between increased risk of urothelial cancers and Aristolochia fangchi (a Chinese herb found in some over-the-counter diet pills).