Renal cell carcinoma

Kidney cancer remains one of the most common cancers in the world, accounting for over 179,000 deaths worldwide in 2020,1 with renal cell carcinoma (RCC) accounting for approximately 90% of all cases.2

RCC occurs when abnormal cells develop in the tissue of the kidneys, specifically in the small tubes (also known as tubules) where our blood is filtered.3 Typically, RCC is a single tumour in one kidney but, in rare cases, there can be multiple tumours, which can occur in one or both kidneys.2

Despite recent progress in the field of kidney cancer, treatment options remain limited in their effectiveness for people with the disease.

There are a number of risk factors associated with the development of RCC. These can be broken down into two groups:4,5

Non-modifiable:

• Incidence increases with age (until around 70 years old)

• Sex (men are more likely to develop RCC than women)

• Presence of other genetic diseases that affect the kidneys

• Modifiable:

• Smoking

• Obesity

• Presence of other medical conditions, such as increased blood pressure

• Occupational exposure to chemicals such as TCE (trichloroethylene), which is used as a metal degreaser and chemical additive

The degree to which a tumour has grown and spread determines the stage classified at diagnosis. Generally, RCC tumours can be categorised as localised, locally advanced or metastatic.3,6

Localised RCC presents a unique challenge as many patients do not experience symptoms at this stage of the disease.3 Nevertheless, early detection rates are acceptable,7 as the disease is often picked up when patients are having abdominal scans for other reasons.8

Whilst the majority of people do not experience any clear symptoms during the earlier stages of the disease, as the tumour grows, the most common symptoms tend to be localised near to the kidneys. The symptoms of RCC may include, but are not limited to:3

• Blood in urine

• Pain in the side

• Abdominal mass

• Fatigue and loss of appetite

• Weight loss

Like all forms of cancer, the stage at which an RCC diagnosis is made has a strong influence on the prognosis.

“If RCC is diagnosed at the localised stage, when the cancer hasn’t yet spread from the kidneys, 93% of people will still be alive after 5 years. However, if diagnosed in the metastatic stage, where over one in ten patients will receive diagnosis, only around 13% survive beyond 5 years,”6 says Dr Constanze Kaiser, Group Global Scientific Director at Roche. “Although, recently, targeted therapies have improved outcomes for patients with metastatic disease, this huge gap in survival rates emphasises the importance of early diagnosis and treatment.”

Various options are available for the treatment of RCC. In the early stages, where the cancer is localised to the kidney, surgery is effective. For people with advanced disease, treatment options can include chemotherapy, targeted therapies and cancer immunotherapies.9

• Surgery: for localised disease, surgery can be curative in up to 90% of patients 10

• Chemotherapy: in patients with a particular type of the disease, sarcomatoid RCC, chemotherapy can be used11

• Immunotherapy: boosts the ability of a person's own immune system to fight, recognise and kill cancerous cells more effectively.12 There are different types of immunotherapies:

  • Checkpoint inhibitors: These therapies remove the ‘brakes’ off the immune system, helping it recognise and attack cancer cells. Checkpoint inhibitors could be used together with other therapies such as tyrosine-kinase inhibitors (TKIs) (please see below) to increase the response against tumours12

  • Cytokine therapy: a type of immunotherapy, cytokine therapy can offer long-term responses in some patients12

• Angiogenesis inhibitors: a targeted therapy that interferes with the formulation of blood vessels which are used by cancerous tumours to grow13

• TKIs: a type of targeted therapy that has become the standard of care for advanced RCC14

“In the metastatic stage, although immune checkpoint inhibitors have improved outcomes for patients, we continue to see cases where patients’ tumours either have primary resistance (they do not initially respond to treatment) or become resistant to treatment after an initial response,”15,16 says Dr Kaiser.

Hence, for people with localised and advanced forms of RCC, it is clear that a need for progress and better treatment options remains.

References

1. World Health Organization. GLOBOCAN 2020 – Kidney fact sheet [Internet; cited 2021 Feb 10]. Available from:.

2. American Cancer Society. What is kidney cancer? [Internet; cited 2021 Feb 10]. Available from:.

3. Cancer.gov. Renal cell cancer treatment (PDQ®) – Patient version [Internet; cited 2021 Feb 10]. Available from:.

4. Ridge CA, et al. Epidemiology and staging of renal cell carcinoma. Semin Intervent Radiol. 2014;31(1):3-8.

5. Chow WH, et al. Epidemiology and risk factors for kidney cancer. Nat Rev Urol. 2010;7(5):245–257.

6. SEER. Stat fact sheets: Kidney and renal pelvis cancer [Internet; cited 2021 Feb 10]. Available from:.

7. King SC, et al. Continued increase in incidence of renal cell carcinoma, especially in young patients and high grade disease: United States 2001 to 2010. J Urol. 2014;191(6):1665–1670.

8. American Cancer Society. Tests for kidney cancer [Internet; cited 2021 Feb 10]. Available from:.

9. American Cancer Society. Treatment of kidney cancer by stage [Internet; cited 2021 Feb 10]. Available from:.

10. BMJ Best Practice. Renal cell carcinoma [Internet; cited 2021 Feb 10]. Available from:.

11. NCCN. NCCN guidelines version 2.2017 kidney cancer [Internet; cited 2021 Feb 10]. Available from:.

12. American Cancer Society. Immunotherapy for kidney cancer [Internet; cited 2021 Feb 10]. Available from:.

13. Cancer.gov. Angiogenesis inhibitors [Internet; cited 2021 Feb 10]. Available from:.

14. American Cancer Society. Targeted therapy for kidney cancer [Internet; cited 2021 Feb 10]. Available from:.

15. Fares CM, et al. Mechanisms of resistance to immune checkpoint blockade: Why does checkpoint inhibitor immunotherapy not work for all patients? Am Soc Clin Oncol Educ Book. 2019;39:147-164.

16. Moreira M, et al. Resistance to cancer immunotherapy in metastatic renal cell carcinoma. Cancer Drug Resist. 2020;3:454-471.