The urinary system is comprised of the kidneys, bladder, ureters, and urethra. The kidneys filter blood to produce urine, which is then transferred to the bladder via the ureters and exits the body through the urethra. The kidneys also have homeostatic roles in regulating blood pressure, acid-base balances and electrolytes.
Cancers of the urinary system are a significant concern in Australia. Kidney cancer is estimated to be the seventh most common cancer in Australia,1 with 4,771 people diagnosed, and 966 deaths in 2024.2,3 The proportion of people surviving for at least five years after diagnosis with kidney cancer is 82%, based on data from the period 2016–2020.4 In Australia, 3,319 people were diagnosed with bladder cancer, and 1,121 deaths occurred from this disease in 2024.2,3 People with bladder cancer have a 57% chance of survival for at least five years.4 For cancers in other urinary organs, 191 people diagnosed with ureteral cancer, and 45 with urethral cancer in 2024.2
Kidney and bladder cancer make life very difficult for people with these conditions. Difficult side effects come from treatments such as radiotherapy, chemotherapy and surgery to remove the bladder. Early menopause and difficulty having sex may also occur.5,6
3.5.4.1 Risk associated with smoking
Smoking causes cancer of the kidney, bladder and renal pelvis (region where the ureter joins the kidney).7-11 The IARC has estimated that 66% of bladder cancers in men and 30% in women are due to smoking.7 In Australia, an estimated 35% of bladder cancers in men and 29% in women are caused by smoking.12 Further Australian data also shows that, for people aged 45 and over, the risk of bladder cancer is over 3-fold higher among those who currently smoke compared to those who do not.13
Several meta-analyses have strengthened these findings.9-11 For example, a meta-analysis published in 2016 found that people who currently smoke had approximately a 3-fold greater risk of developing bladder cancer compared to those who had never smoked.10 Moreover, a meta-analysis investigating the relationship between smoking and kidney cancer estimated that people who smoke had a 1.39-fold greater risk of developing kidney cancer compared to people who had never smoked.9
3.5.4.2 How tobacco smoke causes kidney, bladder and ureter cancers
Aromatic amines, including 2-naphthylamine and 4-aminobiphenyl, are known bladder carcinogens found in cigarette smoke. These compounds are believed to form DNA adducts which have the potential to cause mutations and subsequently cancer in the bladder.7,14
3.5.4.3 Factors affecting risk
Intensity and duration and smoking
A 2005 meta-analysis of 24 studies concluded that the risk of renal cell carcinoma increases with smoking intensity and declines after quitting.15 A later meta-analysis showed that the risk of kidney cancer rose non-linearly with smoking intensity; even smoking only a few cigarettes per day significantly increased the risk.9
The risk of bladder, renal pelvis, and ureter cancers increases with the amount of tobacco consumed and the duration of smoking. For bladder cancer there appears to be a levelling off of risk at high daily consumption levels, possibly due to under-reporting of consumption by heavy smokers.7,16 A 2022 meta-analysis also found that the risk of bladder cancer increased with the number of cigarettes smoked per day, but when smoking intensity reached 20 cigarettes smoked per day, the risk of bladder cancer plateaued. This plateau was not observed with pack-years of smoking or duration of smoking.16 A pooled analysis of 15 case–control studies showed that for a fixed number of pack-years, smoking for a longer duration at a lower intensity was more deleterious for bladder cancer risk than smoking more cigarettes per day for a shorter duration.17
Gender differences
Smoking appears to be more strongly associated with the risk of bladder cancer in women than in men. The reasons for this may be differences in metabolism, smoking behaviours, exposure patterns and DNA repair mechanisms between the genders.18
Family history
Emerging evidence from a large cohort study suggests that the combination of smoking and a family history of bladder cancer may have a synergistic effect on risk.19
Smoking cessation
Smoking cessation reduces the risk of bladder and kidney cancers.20 The risk of bladder cancer declines after smoking cessation, rapidly in the first one to four years. However, even after 25 years the risk is not as low as among people who never smoke.7
3.5.4.4 Impact of smoking on prognosis
A 2022 meta-analysis assessing the impact of smoking on non-muscle invasive bladder cancer outcomes, found that people who smoke had a greater risk of disease progression and recurrence compared to those who had never smoked.21
People with bladder cancer who smoke have a lower chance, compared to those who do not smoke, of their chemotherapy treatment working well, which is a strong predictor of survival.22,23 Additionally, people with bladder cancer who smoke have been found to have a 1.87-fold higher risk of major complications after bladder removal surgery, compared to patients who did not smoke.24
A meta-analysis of 14 studies showed that active smoking was associated with poorer outcomes for people with renal cell carcinoma.25 A Japanese study of 963 people with renal cell carcinoma showed that smoking 20 or more cigarettes per day at diagnosis was associated with poorer overall and cancer-specific survival.26
Related reading
Test your knowledge
References
1.Australian Institute of Health and Welfare. Cancer data in Australia. Canberra: AIHW. 2024. Available from: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia.
2. Australian Institute of Health and Welfare. Cancer data in Australia. Data tables: CDIA 2024: Book 1a – Cancer incidence (age-standardised rates and 5-year age groups) Canberra: AIHW. 2024. Available from: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/data.
3. Australian Institute of Health and Welfare. Cancer data in Australia. Data tables: CDIA 2024: Book 2a – Cancer mortality (age-standardised rates and 5-year age groups) Canberra: AIHW. 2024. Available from: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/data.
4. Australian Institute of Health and Welfare. Cancer data in Australia. Data tables: CDIA 2024: Book 3a – Cancer survival summary (observed, relative and conditional estimates) Canberra: AIHW. 2024. Available from: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/data.
5. Cancer Council Australia. Understanding kidney cancer, 2022, Cancer Council Australia. Available from: https://www.cancer.org.au/assets/pdf/understanding-kidney-cancer-booklet.
6. Cancer Council Australia. Understanding bladder cancer, 2024, Cancer Council Australia: Sydney, Australia. Available from: https://www.cancer.org.au/assets/pdf/understanding-bladder-cancer-booklet.
7. International Agency for Research on Cancer Working Group on the Evaluation of Carcinogenic Risks to Humans. Tobacco smoke and involuntary smoking. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Volume 83. Lyon: International Agency for Research on Cancer. 2004. Available from: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Tobacco-Smoke-And-Involuntary-Smoking-2004.
8. US Department of Health and Human Services. The health consequences of smoking: a report of the Surgeon General. Atlanta, Georgia: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2004. Available from: https://archive.cdc.gov/www_cdc_gov/tobacco/sgr/2004/index.htm.
9. Liu X, Peveri G, Bosetti C, Bagnardi V, Specchia C, et al. Dose-response relationships between cigarette smoking and kidney cancer: A systematic review and meta-analysis. Critical Reviews in Oncology/Hematology, 2019; 142:86-93. Available from: https://www.ncbi.nlm.nih.gov/pubmed/31387065
10. van Osch FH, Jochems SH, van Schooten FJ, Bryan RT, and Zeegers MP. Quantified relations between exposure to tobacco smoking and bladder cancer risk: a meta-analysis of 89 observational studies. International Journal of Epidemiology, 2016; 45(3):857-70. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27097748
11. Cumberbatch MG, Rota M, Catto JW, and La Vecchia C. The Role of Tobacco Smoke in Bladder and Kidney Carcinogenesis: A Comparison of Exposures and Meta-analysis of Incidence and Mortality Risks. European Urology, 2015. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26149669
12. Pandeya N, Wilson LF, Bain CJ, Martin KL, Webb PM, et al. Cancers in Australia in 2010 attributable to tobacco smoke. Australian and New Zealand Journal of Public Health, 2015; 39(5):464-70. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26437733
13. Weber MF, Sarich PEA, Vaneckova P, Wade S, Egger S, et al. Cancer incidence and cancer death in relation to tobacco smoking in a population-based Australian cohort study. International Journal of Cancer, 2021; 149(5):1076-88. Available from: https://www.ncbi.nlm.nih.gov/pubmed/34015143
14. US Department of Health and Human Services. How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease. A report of the US Surgeon General Atlanta, Georgia: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2010. Available from: https://www.ncbi.nlm.nih.gov/books/NBK53017/.
15. Hunt JD, van der Hel OL, McMillan GP, Boffetta P, and Brennan P. Renal cell carcinoma in relation to cigarette smoking: meta-analysis of 24 studies. International Journal of Cancer, 2005; 114(1):101-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15523697
16. Zhao X, Wang Y, and Liang C. Cigarette smoking and risk of bladder cancer: a dose-response meta-analysis. International Urology and Nephrology, 2022; 54(6):1169-85. Available from: https://www.ncbi.nlm.nih.gov/pubmed/35332429
17. van Osch FHM, Vlaanderen J, Jochems SHJ, Bosetti C, Polesel J, et al. Modeling the complex exposure history of smoking in predicting bladder cancer: A pooled analysis of 15 case-control studies. Epidemiology, 2019; 30(3):458-65. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30601243
18. Janisch F, Shariat SF, Schernhammer E, Rink M, and Fajkovic H. The interaction of gender and smoking on bladder cancer risks. Current Opinion in Urology, 2019; 29(3):249-55. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30888973
19. Kim HJ, Kim KH, Lee SW, Swan H, Kazmi SZ, et al. Familial risk and interaction with smoking and alcohol consumption in bladder cancer: A population-based cohort study. World Journal of Oncology, 2023; 14(5):382-91. Available from: https://www.ncbi.nlm.nih.gov/pubmed/37869241
20. US Department of Health and Human Services. Smoking cessation. A report of the Surgeon General. Atlanta, GA U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Centre for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health 2020. Available from: https://www.cdc.gov/tobacco-surgeon-general-reports/reports/2020-smoking-cessation/.
21. Slusarczyk A, Zapala P, Zapala L, and Radziszewski P. The impact of smoking on recurrence and progression of non-muscle invasive bladder cancer: a systematic review and meta-analysis. Journal of Cancer Research and Clinical Oncology, 2023; 149(6):2673-91. Available from: https://www.ncbi.nlm.nih.gov/pubmed/36404390
22. Gild P, Vetterlein MW, Seiler R, Necchi A, Hendricksen K, et al. The association of cigarette smoking and pathological response to neoadjuvant platinum-based chemotherapy in patients undergoing treatment for urinary bladder cancer - A prospective European multicenter observational study of the EAU Young Academic Urologists (YAU) urothelial carcinoma working group. Surgical Oncology, 2020; 34:312-7. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32891350
23. He T, Hu J, Qiu D, Deng H, Hu J, et al. Smoking status and pathological response to neoadjuvant chemotherapy among patients with bladder cancer: a pooled analysis. Translational Andrology and Urology, 2021; 10(1):374-83. Available from: https://www.ncbi.nlm.nih.gov/pubmed/33532325
24. Tellini R, Mari A, Muto G, Cacciamani GE, Ferro M, et al. Impact of smoking habit on perioperative morbidity in patients treated with radical cystectomy for urothelial bladder cancer: A systematic review and meta-analysis. European Urology Oncology, 2021; 4(4):580-93. Available from: https://www.ncbi.nlm.nih.gov/pubmed/33160975
25. Xu Y, Qi Y, Zhang J, Lu Y, Song J, et al. The impact of smoking on survival in renal cell carcinoma: a systematic review and meta-analysis. Tumour Biology, 2014; 35(7):6633-40. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24699995
26. Hara T, Fujimoto H, Kondo T, Shinohara N, Obara W, et al. Active heavy cigarette smoking is associated with poor survival in Japanese patients with advanced renal cell carcinoma: sub-analysis of the multi-institutional national database of the Japanese Urological Association. Japanese Journal of Clinical Oncology, 2017; 47(12):1162-9. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29121328