Kidney Cancer

What is Kidney Cancer?

Kidney cancer refers to cancer that starts in the kidney and cancer occurs when there is uncontrolled growth of cells. Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for 9 in 10 cases.

There are several subtypes of RCC such as clear cell RCC, non-clear cell RCC. Clear cell RCC is the commonest type of RCC accounting for 7 in 10. Non-clear cell RCC includes a group of less common types of RCC such as papillary, chromophobe and collecting duct for example.

Other types of kidney cancer include Transitional cell carcinoma (TCC) which can arise from cells that line the renal pelvis. Apart from RCC and TCC, there are also rare kidney cancers such as Wilms tumour in children and renal sarcoma. There are also benign (non-cancerous) kidney cancers including angiomyolipoma and oncocytoma.

This article will be focussing on clear cell RCC.

What are Risk Factors for RCC?

Gender: RCC is twice as common in men than women
Age: Peak incidence between 60-80
Chronic kidney disease / dialysis
Smoking
Occupational exposure to toxic compounds such as petrochemical by-products, cadmium or asbestos
Hypertension
Obesity
Analgesics use (Aspirin, non-steroidal anti-inflammatory, Acetaminophen)
Hereditary genetic predisposition: a small portion of RCC is due to rare underlying genetic condition such as Von Hippel-Lindau (VHL) disease, hereditary papillary renal cell carcinoma, tuberous sclerosis, Hereditary BAP-1
Hepatitis C

In many cases, the cause of RCC is not known. Things that can reduce your risk include maintaining a healthy lifestyle by not smoking, exercising, increasing dietary intake of fruits and vegetables and avoiding harmful exposure to toxic chemicals.

Screening and Symptoms of RCC

There is no cost-effective screening test for detection of kidney cancers for average-risk individuals. Many kidney cancers are found incidentally in the early stage during abdominal imaging for other causes. Small kidney cancers tend to cause no signs or symptoms. Sometimes kidney cancers are only found in advanced stages as they can grow to a relatively large size before causing pain or other symptoms. Signs and symptoms of advanced kidney cancers may include:

Blood in urine
Pain or swelling over loin
Fatigue due to low red cell count
Weight loss

Diagnosis and Staging: How to Screen for Kidney Cancer?

Detailed imaging tests allow visualisation of the kidney cancer and involvement of adjacent lymph nodes, blood vessels and distant spread. Computer tomography (CT) is cross-sectional imaging routinely performed to obtain such information. Occasionally, magnetic resonance imaging (MRI) is performed when more detailed visualisation of the extent of direct growth of cancer into adjacent large veins or other organs is desired. Bone scan and MRI brain may be done to exclude spread to bone or brain respectively. If needed, a needle biopsy may also be performed under CT guidance. In some cases, surgeons may proceed straight to surgery based on imaging findings alone.

How is The Stage of Kidney Cancer Determined?

Stage of kidney cancer is determined by size, extent of tumour growth into adjacent areas, spread into nearby lymph nodes and spread to distant sites. For stage 4 RCC, additional prognostication scores can be assigned based on laboratory results (neutrophil, platelet, haemoglobin, calcium) and patient factors (less than a year from time of diagnosis to need for drug treatment, patient’s fitness level).

Treatment

1. Surgery

Surgery for RCC can be done via an open or laparoscopic (keyhole) /robotic approach.

Partial nephrectomy: Only part of the kidney that contains the tumour is removed. This surgery is suitable for patients who are at risk of loss of significant renal function, with tumours that are less than 7cm in size and located away from the centre of the kidney without invasion into a large vein.
Radical nephrectomy: The whole kidney is removed together with adjacent fat. lymph nodes. Occasionally, the surrounding lymph nodes and/or adrenal gland above the kidney may also be removed.

Removal of the kidney may be considered even for patients with stage 4 RCC, usually in situations where there are local symptoms such as pain or bleeding. For stage 4 RCC patients with limited sites of spread, surgical removal or local ablation of all sites may be an appropriate consideration especially in patients with favourable prognostic scores.

2. Adjuvant Treatment

In resectable early stage RCC, the role of oral targeted therapy after surgery (adjuvant treatment) remains controversial based on data from many contemporary trials. KEYNOTE 5643 clinical trial presented in mid 2021 showed that 1 year of adjuvant Pembrolizumab (immunotherapy) in patients with resected kidney cancer significantly reduces relapse risk by 32%. This treatment offers a very good option for patients at higher risk of relapse.

3. Systemic Therapy

Systemic therapy refers to the use of drugs to treat RCC. Patients with stage 4 RCC are not amenable to curative intent surgery or local ablation will be candidates for systemic therapy. RCC tends to respond poorly to conventional chemotherapy. For almost a decade, targeted therapy blocking growth of new blood vessels (angiogenesis) and other important growth/survival proteins in cancer cells was the mainstay of treatment in RCC. Targeted therapy, which is mostly available in convenient oral formulation, was typically used in sequence one after another. Immunotherapy has transformed the treatment of RCC starting with the 2015 publication of Nivolumab in Checkmate 0251 trial in patients who have failed 1 prior targeted therapy. Since 2018, a flurry of impressive data of frontline combination treatment with dual immunotherapy2 or immunotherapy plus targeted therapy 4,5,6,7 completely changed the outlook of patients with stage 4 RCC. The benefit of upfront treatment with immunotherapy-based combination is most pronounced in the subgroup of patients with poorer prognostic features, who historically respond poorly to targeted therapy alone. When deciding on a treatment option, there are many factors that may impact treatment decision for RCC including:

Multiple tumours in one kidney or bilateral kidney tumours
Underlying genetic condition
Solitary kidney or compromised kidney function
Suspected involvement of lymph node
Extent of direct tumour invasion into large vein or adrenal gland
Extent of cancer spread
Patient’s fitness level and life expectancy

Close observation may be reasonable for small lesions lesser than 4cm in patients with limited life expectancy. Alternatively, other less invasive approaches with less impact on kidney function such as cryotherapy, radiofrequency ablation or surgical enucleation of tumour alone can be considered.

Conclusion

RCC is a very diverse cancer. Huge inroads into better understanding of the biology of RCC and treatment has been achieved over the years. When it comes to treatment decisions, they are highly complex and need to be individualised to each patient. Major advancement in new drugs for treatment of RCC in the past decade, has turned a disease that is historically chemotherapy refractory, to a condition that is very treatable.

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