Renal cell carcinoma (RCC) is a cancer of the kidneys. It is the most common type of kidney cancer (upto 85%) in the adult (other rare forms exist). It begins in the renal cortex. In children, Wilm’s tumor is the most common type of renal cancer.

Statistics show more than 60,000 new cases are diagnosed each year with nearly 15,000 deaths. It is slightly more common in men and the usual age of occurrence is between 50-70 years.

Causes/Risk factors of Renal Cell carcinoma (RCC)
The exact etiology of renal cell carcinoma is not clear although several factors have been associated with an increased risk of renal cell cancer that include the following.

• Increasing age
• Smoking
• High blood pressure (hypertension)
• Obesity and high body mass index (BMI)
• Family history of renal cancer
• Dialysis patients who develop cystic disease
• Phenacetin abuse
• Inherited syndromes – Hereditary papillary renal cell cancer, familial renal cancer, von Hippel-Lindau disease, Birt-Hogg-Dube syndrome, tuberous sclerosis complex,
• Occupational exposure to cadmium or certain chemicals

Clinical features of RCC
RCC is usually not symptomatic in the initial stages and is often not diagnosed until later when it becomes symptomatic. These include

• Blood in the urine (hematuria), which may appear dark brown or red in colour
• Persistent pain in the flank
• Hypertension in some cases
• Loss of appetite
• Unexplained weight loss
• Tiredness
• Unexplained fever, which usually comes and goes (intermittent)

About 20 percent of renal cancer patients develop paraneoplastic syndromes due to abnormal ectopic secretion of hormones by the tumor. These include polycythemia (erythropoietin secretion), hypercalcemia (common).

Diagnosis of Renal Cell Carcinoma
As mentioned earlier, renal cell cancer is asymptomatic in the initial stages and may be picked up incidentally during an abdominal CT or ultrasound done for other purposes.

• Renal Imaging
In symptomatic patients, if the history and physical examination raises suspicion about possible malignancy, it may be confirmed by abdominal CT with and without contrast or an MRI scan. A renal lesion that is enhanced by radiocontrast dye is strongly suggestive
of an RCC.

MRI scan provides further information regarding extension into the renal vein or the inferior vena cava (IVC). Nowadays CT and MRI have largely replaced abdominal ultrasound or intravenous urogram (IVU) to outline the characteristics of renal cancer.

• Renal Biopsy
Usually, specialized imaging studies such as CT and MRI scans can distinguish between benign and cancerous lesions of the kidney. However, in certain cases, a renal biopsy may be necessary to confirm the diagnosis

• Blood Tests
Renal function status is assessed by measuring serum creatinine, BUN, electrolytes and calcium. Liver function is also measured. If serum alkaline phosphatase levels are increased, a bone scan may be recommended to rule out bone secondaries.

• Chest x-ray
A chest x-ray will demonstrate any suspicious lung deposit and further information may be obtained by a chest CT.

Staging of Renal Cell Carcinoma
Clinical staging of RCC is important to plan management. The AJCC/TNM system is most often employed. The 4 stages of renal cancer are as follows

• Stage I – The tumor can be up to 7 centimeters in diameter and limited to the kidney.
• Stage II – Stage II kidney cancer is larger than a stage I tumor, but still confined to the kidney.
• Stage III – The tumor extends beyond the kidney to the adjacent tissues and regional lymph nodes may also be involved by tumor
• Stage IV – The cancer has spread outside the kidney, to multiple lymph nodes or to distant parts of the body including liver, bones and lungs

As per available statistics, nearly 25 percent of RCCs have spread to distant sites at the time of diagnosis.

Treatment of Renal Cell Carcinoma
Treatment of RCC depends on the type of RCC, the general condition of the patient and most importantly the disease stage.

Early kidney cancers are treated by curative surgery or non-surgical approach for small tumors. Advanced cancers are managed with palliative measures and newer experimental protocols.

Localised RCC – Curative treatments
Generally, radical nephrectomy (removal of kidney, adrenal gland, perirenal fat, and Gerota fascia) is standard treatment for localized RCC and provides a reasonable chance for cure. However, in smaller tumors less than 7 cms, nephron-sparing surgery (partial nephrectomy) is preferred and appropriate for many patients. Partial nephrectomy is gaining popularity because it results in a lower incidence of chronic kidney disease than radical nephrectomy.
Nonsurgical ablation of renal cancer by freezing (cryosurgery) or thermal energy (radiofrequency ablation) are not currently recommended as first line treatment. They are being done in highly select group of patients, but more data needs to be made available regarding safety, efficacy and patient selection.

As per latest guidelines, for localised RCC, surgery is usually sufficient with periodic followup.

Advanced RCC – Palliative measures
In most patients with metastatic disease, nephrectomy is palliative and systemic treatments may be necessary.

Surgical
Palliative surgery to reduce pressure symptoms can include nephrectomy, tumor embolization. Resection of metastases offers palliation and, if limited could prolong life in some patients, particularly those with a long interval between initial treatment (nephrectomy) and development of metastases.

Radiotherapy
Although metastatic RCC is typically considered to be radioresistant, radiotherapy can be palliative in bone or brain metastases of RCC. Radiation therapy employs high-powered energy beams, such as X-rays, to kill cancer cells

Biological therapy or immunotherapy
This modality involves the use of agents that boost the immune system to kill cancer cells. Biological agents include interferon and aldesleukin (Proleukin), which are synthetic versions of natural chemicals synthesized in the body. Nivolumab (Opdivo) is a biologic agent that has recently been used in the treatment of advanced RCC. Nivolumab which has been found to have a better overall survival than sunitinib. Results of trials are awaited

Targeted therapy
Targeted treatments block certain abnormal signals occurring in cancer cells that enable them to multiply and spread.
Many targeted therapies for advanced tumors including sunitinib (angiogenesis inhibitor), bevacizumab, sorafenib, pazopanib, cabozantinib, axitinib, and lenvatinib (tyrosine kinase inhibitors) and temsirolimus and everolimus, which inhibit the mammalian target of rapamycin (mTOR) have been found to be promising.

Experimental treatments:
Experimental treatments for RCC include angiogenesis inhibitors (thalidomide), stem cell transplantation and vaccine therapy.

With increasing information on the genetic subtypes of RCC, more specific treatment recommendations are being trialled.