Can Recurrent UTI Symptoms Be a Sign of Cancer?

Urinary tract infections (UTIs) are much more common in women than in men, and the symptoms, e.g. blood in urine, can be similar to bladder cancer, reinforcing the importance of an accurate diagnosis. Here we give an overview of UTIs and discuss why it is important to rule out bladder cancer if you are experiencing recurring UTI symptoms.

• What Causes UTIs
• Common UTI Symptoms
• How Are UTIs Treated
• Why UTIs Keep Coming Back
• What Can Mimic a UTI
• Bladder Cancer Signs and Symptoms in Women
• What Causes Bladder Cancer
• Bladder Cancer Risk Factors
• Can UTIs Increase the Risk of Bladder Cancer
• The Problem of Misdiagnosis in Women With Bladder Cancer
• If You Are Concerned About Bladder Cancer, Speak To Your Doctor About Cxbladder

What Causes UTIs?

UTIs usually occur when bacteria enter the urethra (the duct through which urine leaves the bladder) and multiply, travelling up the urinary tract. Infection most commonly develops in the urethra and bladder (the ‘lower urinary tract’), though in some instances the infecting bacteria may spread further upwards to the ureter (the duct through which urine enters the bladder) and kidney. Note that a lower urinary tract infection is often referred to simply as a ‘bladder infection’ or cystitis. 

UTIs are considerably more common in women than men because of their differing anatomy:

• Women have a shorter distance between the urethral opening and the perianal area, which increases their vulnerability to the spread of gastrointestinal bacteria such as E. coli.
• The length of the urethra in women is relatively short compared with men, making it easier for bacteria to reach the bladder.

Common UTI Symptoms

Most UTIs occur in the bladder and urethra and are associated with signs and symptoms that may include a frequent need to urinate, a painful or burning sensation when passing urine, strong smelling urine, urine with a cloudy appearance, blood in the urine (hematuria), and pain in the pelvic area.

Less commonly, UTIs reach the ureters and kidneys where they may cause symptoms such as upper back and side pain, fever/chills, nausea, and vomiting. Kidney infections may lead to life-threatening complications and/or permanent kidney damage, so it is essential to seek medical treatment immediately if experiencing these symptoms.

How Are UTIs Treated?

UTIs are usually treated with antibiotics. To help avoid the recurrence of a UTI, it is important to ensure that the full antibiotic course is completed.

Can UTI symptoms linger after antibiotic treatment?

If antibiotic treatment has been effective, UTI symptoms should be fully resolved. When symptoms persist at completion of the prescribed antibiotic course, further tests and treatment will be necessary. This may involve culturing a urine sample to determine which antibiotic types are effective against the infecting bacteria, and the use of diagnostic imaging (e.g., an ultrasound scan) to check the urinary tract.

How long can a UTI go untreated?

If you ever see blood in your urine or are concerned about other UTI signs and symptoms, contact your doctor. Seeking treatment promptly not only decreases the chance of UTI-related complications, but also helps to avoid extended periods of misdiagnosis if your symptoms are not being caused by a UTI.

If symptoms such as back pain, fever, and nausea/vomiting are present always seek urgent treatment, because of the risk of permanent kidney damage and/or life-threatening complications.

Why UTIs Keep Coming Back

It is estimated that 50% of women who encounter a UTI go on to experience a recurrence of infection within a year³.  Some individuals have multiple UTI episodes throughout their life, and a few suffer from chronic UTIs. Factors that may increase the chance of UTI recurrence include:

• Sexual intercourse
• Certain types of birth control, particularly diaphragms and spermicidal agents
• Inherent predisposition: some women have urinary tracts that are more prone to bacterial invasion
• Anatomical abnormalities or blockages (e.g., due to kidney stones) in the urinary tract
• Immune suppression caused by diseases such as diabetes
• Post-menopausal changes in the vaginal lining and in the ability of the bladder to contract

What Can Mimic a UTI?

So, if it's not a UTI, what else could it be? Several other infectious and non-infectious disease processes can cause symptoms that mimic a UTI. These include conditions such as vaginitis, overactive bladder, and kidney stones; some sexually transmitted infections (STIs); and diseases such as bladder cancer.  Due to the potentially serious consequences of many of these alternate diagnoses, it is important that recurrent UTI-like symptoms are thoroughly investigated.

Bladder Cancer Signs and Symptoms in Women

 Blood in the urine (hematuria)

• Blood in the urine is the most common sign of bladder cancer and is also often the first sign noticed. This is because early bladder cancer frequently causes bleeding without pain or other symptoms.
• Depending on the amount of blood present, the urine may appear pink, red, or brownish in color. When blood is present at levels not visible to the naked eye it is referred to as ‘microhematuria’. Microhematuria is detected by laboratory urine tests.
• It is important to note that hematuria also occurs commonly in people who do not have bladder cancer. In one study, only about 10% of people with visible hematuria were diagnosed with bladder cancer.⁷

A change in urination habits and/or symptoms of irritation, such as:

• Increased frequency (e.g., needing to urinate several times during the night)
• Pain or a burning sensation during urination
• Increased urgency
• Difficulty passing urine

Bladder cancer that has grown in size or spread to other areas of the body may cause a variety of symptoms including an inability to pass urine, lower back pain on one side of the body, pain in the pelvic region, appetite/weight loss, general weakness, swollen feet, or bone pain.

If you have noticed any of these symptoms and are concerned, visit your doctor and ask about testing options, including Cxbladder. Cxbladder is a non-invasive genomic urine test that can quickly and accurately rule out urothelial bladder cancer in patients presenting with hematuria, reducing the need for further invasive procedures.
Learn more about Cxbladder

What Causes Bladder Cancer? 

Bladder cancer occurs when cells making up the bladder begin to grow and spread in an uncontrolled way, leading to the formation of a malignant tumor. This abnormal cell growth is caused by mutations in the genes that control cell replication, repair, and programmed death: genes that help cells to grow and divide may be switched on, whereas genes that regulate cell division, repair, and programmed death may be switched off.

Most of the gene mutations associated with bladder cancer are ‘acquired’, meaning that they develop during a person’s life rather than being present at birth (‘inherited’). Some of the acquired gene mutations are caused by exposure to toxins or chemicals that are recognized risk factors for developing bladder cancer, such as tobacco smoke.

Bladder Cancer Risk Factors 

Factors associated with an increased chance of developing bladder cancer include: 

• Sex: Men are 4 times more likely than women to be diagnosed with bladder cancer.
• Age: Bladder cancer mostly affects people >55 years of age. In the United States, the average age of individuals diagnosed with bladder cancer is 73 years.
• Race: White Americans are approximately 2 times more likely to to have bladder cancer detected compared with African Americans and people of Hispanic ethnicity, while Asian Americans and Native Americans have the lowest rates.
• Smoking: Cigarette smoking is the most important risk factor for bladder cancer, causing around half of all cases. Smokers are at least 3 times as likely to get bladder cancer compared with non-smokers.
• Exposure to certain chemicals in the workplace: Aromatic amines used in the dye industry and organic chemicals used in the production of rubber, leather, paint and textiles may contribute to a higher bladder cancer rates in workers. Painters, printers, hairdressers, and truck drivers are also at increased risk due to workplace exposures.
• Arsenic in drinking water: The likelihood of potentially harmful levels of arsenic in drinking water depends on the water source being used.
• Some medicines: The use of some medicines and certain chemotherapy drugs may be associated with increased bladder cancer risk.
• Previous bladder cancer: People who have had bladder cancer are prone to recurrence.

Can UTIs Increase the Risk of Bladder Cancer?

Several studies have investigated whether UTIs may be a risk factor for bladder cancer.

• Epidemiological studies that have examined evidence of an association between UTIs and urothelial carcinoma (a cancer which begins in urothelial cells of the urinary tract and accounts for approximately 90% of bladder cancer cases) have to date produced varying results.^3,13,14 Some data indicates there may be an increased risk in individuals who experience previous UTIs,^3,14 whereas other findings suggest that previous UTIs could have a protective effect against bladder cancer, possibly due to an anti-cancer effect of the antibiotics used in their treatment.^3,13,14
• Colibactin, a bacterial toxin that can damage DNA, is suspected to play a role in some types of cancer. Researchers have recently detected colibactin production in E. coli isolated from the urine of patients with UTIs.¹⁵ Furthermore, in the urinary tracts of mice infected with colibactin-producing E. coli, DNA damage in bladder cells was observed (which included damage to urothelial cells involved in regenerating the lining of the bladder).
• Preliminary data appears to support a link between recurrent UTIs and increased risk of squamous cell carcinoma of the bladder.¹⁶ However, as squamous cell carcinoma is a rare type of bladder cancer (<5% of cases), the overall impact of this potential association would be relatively minor.

It may be concluded that the extent of any direct relationship between UTIs and bladder cancer is yet to be fully determined. However, it is clear that a major bladder cancer risk associated with recurrent UTIs in women is that of delayed diagnosis, caused by the extensive overlap in symptoms between the two conditions.

The Problem of Misdiagnosis in Women With Bladder Cancer 

While bladder cancer is more common in men than in women, women often present with more advanced tumors and their overall survival rate is lower.¹⁷ 

A major reason for women presenting with more advanced tumors is the delay that can occur before receiving a bladder cancer diagnosis. Reasons for this delay may include:

• Blood in the urine, the most common symptom of bladder cancer, may be discounted by women as being related to menstruation or post-menopausal bleeding.
  
• When blood in the urine and urinary irritation are reported to a doctor they may be initially misdiagnosed as a UTI. Additionally, if a woman subsequently presents after treatment failure for a misdiagnosed UTI, further antibiotics may be prescribed rather than carrying out a complete urological evaluation.
  
• UTIs and bladder cancer can occur at the same time, in which case the UTI will be the logical first diagnosis.
  

Because of this diagnostic confusion, a definitive diagnosis of bladder cancer may be delayed in some women. Of particular concern in this case is the risk that bladder cancer has reached a more advanced stage that may be more difficult to treat.

If You Are Concerned About Bladder Cancer, Speak To Your Doctor About Cxbladder

Early detection saves lives and is a crucial factor when it comes to the treatment of bladder cancer. If you're concerned, speak to your doctor.

Cxbladder is a clinically proven cutting-edge genomic urine test that quickly and accurately rules out urothelial bladder cancer in patients presenting with blood in the urine. The test works at a molecular level, measuring five biomarker genes to help rule out the disease, reducing the need for further invasive procedures.

Cxbladder gives you peace of mind and will help your doctor make informed treatment decisions. Speak to your general practitioner or urologist to learn more about Cxbladder and which test might be right for you. You can also contact our Customer Service Team directly.
Learn more about Cxbladder     Contact Us for more information

References

¹ Urinary Tract Infections in Adults. Urology Care Foundation. www.urologyhealth.org/urologic-conditions/urinary-tract-infections-in-adults#Treatment. Published April 2019.

² Urinary tract infection (UTI). Mayo Clinic. www.mayoclinic.org/diseases-conditions/urinary-tract-infection/symptoms-causes/syc-20353447. Published January 30, 2019.

³ Vermeulen SH, Hanum N, et al. Recurrent urinary tract infection and risk of bladder cancer in the Nijmegen bladder cancer study. Br J Cancer. 2015; 112(3), 594-600. Available from: www.ncbi.nlm.nih.gov/pmc/articles/PMC4453642/.

⁴ Adult Urinary Tract Infections. Department of Urology, University of Wisconsin School of Medicine and Public Health. http://urology.wisc.edu/wp-content/uploads/2018/10/Module_2_Adult_UTI.pdf Published July 2016.

⁵ Bladder Cancer: Symptoms and Signs. ASCO Cancer.Net. www.cancer.net/cancer-types/bladder-cancer/symptoms-and-signs. Published May 2019.

⁶ Bladder Cancer Signs and Symptoms. American Cancer Society. www.cancer.org/cancer/bladder-cancer/detection-diagnosis-staging/signs-and-symptoms.html Published. January 30, 2019.

⁷ Patient Education: Bladder Cancer Diagnosis and Staging (Beyond the Basics). UpToDate. www.uptodate.com/contents/bladder-cancer-diagnosis-and-staging-beyond-the-basics. Published April 9, 2019.

⁸ What Causes Bladder Cancer? American Cancer Society. www.cancer.org/cancer/bladder-cancer/causes-risks-prevention/what-causes.html. Published January 30, 2019.

⁹ Bladder Cancer: Risk Factors. ASCO Cancer.Net. www.cancer.net/cancer-types/bladder-cancer/risk-factors. Published May 2019.

¹⁰ Bladder Cancer Risk Factors. American Cancer Society. www.cancer.org/cancer/bladder-cancer/causes-risks-prevention/risk-factors.html. Published January 30, 2019.

¹¹ Key Statistics for Bladder Cancer. American Cancer Society. www.cancer.org/cancer/bladder-cancer/about/key-statistics.html. Published January 8, 2020.

¹² Bladder Cancer: Introduction. ASCO Cancer.Net. www.cancer.net/cancer-types/bladder-cancer/introduction. Published May 2019.

¹³ Jiang X, Castelao JE, et al. Urinary tract infections and reduced risk of bladder cancer in Los Angeles. Br J Cancer. 2009; 100(5), 834-9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653778/.

¹⁴ Bayne CE, Farah D, Herbst KW, Hsieh MH. Role of urinary tract infection in bladder cancer: a systematic review and meta-analysis. World J Urol. 2018;36(8):1181-1190.

¹⁵ Chagneau CV, Massip C, et al. Uropathogenic E. coli induces DNA damage in the bladder. PLoS Pathog. 2021; 17(2): e1009310. Available from: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009310

¹⁶ Pottegård A, Kristensen KB, et al. Urinary tract infections and risk of squamous cell carcinoma bladder cancer: A Danish nationwide case-control study. Int J Cancer. 2020;146(7):1930-1936.

¹⁷ Women & Bladder Cancer. Bladder Cancer Advocacy Network (BCAN). http://bcan.org/women-bladder-cancer/. Publication date not stated.

¹⁸ Bladder Cancer Survival Differences for Women. Bladder Cancer Advocacy Network (BCAN) Webinar. http://bcan.org/wp-content/uploads/2020/01/Survival-Differences-for-Women-with-Bladder-Cancer.pdf. Published 2020.

¹⁹ Survival Rates for Bladder Cancer. American Cancer Society. www.cancer.org/cancer/bladder-cancer/detection-diagnosis-staging/survival-rates.html. Published January 8, 2020.