oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Synonyms: RCC, hypernephroma, Grawitz' tumour
Renal cell carcinoma (RCC) is the most common of the tumours of the kidney in adults, accounting for 86% of neoplasms arising from the kidney. In children, Wilms' tumour is the most common. Benign tumours of the kidney are rare. RCC originates from the proximal renal tubular epithelium. Renal cancer occurs in hereditary and non-hereditary forms, both of which are associated with structural alterations of the short arm of chromosome 3 (3p). RCC can be further subdivided into:
- Clear cell (80-90%)
- Papillary (10-15%)
- Chromophobe (4-5%)
- Collecting duct carcinoma (1%)
- Renal cancers account for approximately 2-3% of all malignancies, with the highest incidence in Western countries.
- Males are more likely to be affected than females, with a ratio of 1.5:1.
- The incidence of kidney cancer begins to rise after the age of 40 and is highest in people aged between 60 and 70 years.
- Several risk factors have been identified, including smoking, obesity, hypertension, long-term dialysis and von Hippel-Lindau disease.
- Hereditary renal cancers tend to be multiple, bilateral and occur at an earlier age than others.
- 2% of sporadic cases have bilateral tumours.
- In the UK there has been an increase of 22% over 10 years while in the USA there has been an increase of 50% in 30 years. There appear to be a number of factors and some are preventable, especially obesity.
- Risk factors include lifestyle, smoking, obesity and hypertension.
- Other risk factors include long-term renal dialysis, tuberous sclerosis, renal transplant recipients, acquired renal cystic disease and von Hippel-Lindau disease.
The use of ultrasound and CT scans has increased the detection of asymptomatic RCC. More than 50% of adult renal tumours are detected when using ultrasound to investigate nonspecific features.
- The classic triad of haematuria, loin pain and loin mass is not often seen now.
- Other presentations include fatigue, weight loss, macroscopic haematuria, palpable mass, varicocele, bilateral ankle oedema, pyrexia of unknown origin and hypertension.
- There is often no abnormality on examination.
- 25-30% of patients present with symptoms of metastatic disease - eg, haemoptysis, bone pain or pathological fracture.
- Paraneoplastic symptoms (eg, neuromyopathy, anaemia, polycythaemia, amyloidosis, elevated ESR, hypercalcaemia and abnormal LFTs) are found in approximately 30% of patients.
The differential diagnosis will depend upon the presentation. There are separate articles Abdominal Masses, Loin Pain and Haematuria that discuss the various causes. There are other histological types of renal tumours and this has influence on prognosis: The other histological types of renal tumours include:
- Transitional cell carcinoma.
- Renal oncocytoma.
- Wilms' tumour.
- Angiomyolipoma - commonly seen in patients with tuberous sclerosis.
- Adenoma - frequently found as an incidental finding at postmortem; if diagnosed during life, it is treated with partial nephrectomy due to histological similarity to adenocarcinoma.
- Urinalysis, cytology, culture and sensitivity should be performed to exclude urinary tract infection.
- Renal function tests; however, if one kidney is functioning well the renal function should be normal.
- FBC may detect iron-deficiency anaemia (from haematuria) or polycythaemia (some renal tumours produce erythropoietin and increase haematocrit).
- LFTs may be abnormal.
- CT renal scanning before and after intravenous contrast is the best initial investigation. MRI or ultrasound scanning may be used if the results are equivocal.
- Enhancements such as multidetector CT 3-dimensional mapping and diffusion-weighted MRI imaging may be helpful to confirm the morphology and identify venous involvement, respectively.
- Intravenous urogram (IVU) may be needed, especially to show any obstruction to flow. IVU is not a good way to search for a clear cell carcinoma.
- Cystoscopy can exclude bladder tumours as a cause of haematuria.
- Renal angiography may possibly be required to assess the blood supply.
- CXR - classical cannon ball secondaries may be seen in the lung. They are discrete circular metastases. Chest CT scan is more sensitive.
- Skeletal survey or bone scan may be required for bone metastases.
- A brain CT scan may also be indicated, depending on symptoms.
- Renal biopsy may be indicated - eg, in patients being treated with surveillance or systemic therapy without previous histopathology.
- Spread is into adjacent structures of the adrenal glands, liver, spleen, colon or pancreas. Local lymph nodes are often involved.
- It may extend into the renal vein and then into the inferior vena cava.
- The lungs are the most common site of metastases. The classical picture of cannon ball secondaries is almost diagnostic.
- It is one of the carcinomas to metastasise to bone where it produces osteolytic lesions.
The current consensus is to use the tumour, node and metastasis (TNM) 2010 system, as recommended by the European Guidelines.
- T: primary tumour.
- TX: primary tumour cannot be assessed.
- T0: no evidence of primary tumour.
- T1: tumour <7 cm in greatest dimension, limited to the kidney.
- T1a: tumour <4 cm in greatest dimension, limited to the kidney.
- T1b: tumour >4 cm but not more than 7 cm in greatest dimension.
- T2: tumour >7 cm in greatest dimension, limited to the kidney.
- T2a: tumour >7 cm in greatest dimension but not more than 10 cm.
- T2b: tumours >10 cm limited to the kidney.
- T3: tumour extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota's fascia
- T3a: tumour grossly extends into the renal vein or its segmental (muscle-containing) branches, or tumour invades the perirenal and/or renal sinus (peripelvic) fat but not beyond Gerota's fascia.
- T3b: tumour grossly extends into the vena cava below the diaphragm.
- T3c: tumour grossly extends into vena cava or its wall above the diaphragm or invades the wall of the vena cava.
- T4: tumour invades beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland).
- N: regional lymph nodes.
- NX: regional lymph nodes cannot be assessed.
- N0: no regional lymph node metastasis.
- N1: metastasis in a single regional lymph node.
- N2: metastasis in more than one regional lymph node.
- M: distant metastasis.
- M0: no distant metastasis.
- M1: distant metastasis.
- Surgery is the basis of treatment, with or without radiotherapy and/or chemotherapy, depending on the stage of the tumour. Radical nephrectomy is no longer the gold standard curative therapy for patients with localised RCC.
- Nephron-sparing surgery should be considered first-line (whenever possible) for patients with a localised tumour less than 4 cm in diameter, an anatomical or functional solitary kidney and patients with a contralateral kidney affected by a condition that might impair renal function in the future. It involves partial nephrectomy with preservation of as much functioning kidney tissue as possible.
- Laparoscopic surgery may be involved and the National Institute for Health and Clinical Excellence (NICE) has reported on both laparoscopic nephrectomy and laparoscopic partial nephrectomy. These should be limited to centres with appropriate expertise. Laparoscopic radical nephrectomy has a lower morbidity compared with open surgery.
- Minimally invasive surgery (eg, image-guided percutaneous radiofrequency (RF) ablation, cryoablation, microwave ablation, laser ablation and high-intensity focused ultrasound ablation) may be an option for patients not suitable for open or laparoscopic surgery with smaller peripheral tumours. NICE has recommended that percutaneous RF ablation, laparoscopic cryotherapy, percutaneous cryotherapy and irreversible electroporation may be used as options in the treatment of kidney cancer. 
- Renal artery embolisation may be used for pre-RF ablation infarction of renal tumours, palliation of unresectable renal malignancy and for renal haemorrhage.
- The adrenal gland can usually be spared, except in the case of a large upper pole tumour in which there is a high risk of adrenal invasion.
- In older patients, the risks of treatment must be weighed against survival rates for the disease. Decision-supporting nomograms have been developed to assist in this respect.
- Tumour nephrectomy is recommended in otherwise fit patients with metastatic disease, combined with interferon-alfa (IFN-alfa).
- Standard chemotherapy is considered ineffective in patients with RCC.
- Immunotherapy - IFN-alfa or interleukin 2 (ILN-2) can be considered in selected patients with a clear cell subtype histology. Aldesleukin (recombinant interleukin-2) is licensed for metastatic RCC, but not for patients with poor performance status and more than one organ with metastatic disease sites, and a period of less than 24 months between initial diagnosis of a primary tumour and date of evaluation of treatment.
- Molecular therapy:
- Some drugs with specific molecular targets have shown benefits in the treatment of advanced RCC.
- Sunitinib (a tyrosine kinase inhibitor) is recommended by NICE as first-line treatment for advanced or metastatic RCC in patients who are suitable for immunotherapy (eg, IFN-alfa-2a), are mobile and are fit enough for light work. Sunitinib inhibits the growth of cancer cells by blocking a group of closely related tyrosine kinase receptors.
- Pazopanib (a tyrosine kinase inhibitor) is recommended by NICE as a first-line treatment option for people with advanced RCC who have not received prior cytokine therapy.
- Everolimus (a protein kinase inhibitor) is not recommended by NICE for the second-line treatment of advanced RCC.
- In August 2009, NICE issued guidance stating that bevacizumab (a monoclonal antibody that inhibits vascular endothelial growth factor), sorafenib and temsirolimus (a protein kinase inhibitor) should no longer be used as first-line treatment for metastatic or advanced disease but may be continued for patients already taking one of these drugs. Sorafenib (an inhibitor of multiple kinases) and sunitinib are not recommended as second-line drug treatments in this group of patients.
- Metastasectomy is recommended where disease is resectable in otherwise fit patients. It should also be performed in patients with residual and resectable metastatic lesions previously responding to immunotherapy and/or a limited (solitary) lesion.
- Radiotherapy for the treatment of brain metastases (whole brain irradiation or stereotactic approach) and osseous lesions may be helpful as palliative therapy in selected patients.
Paraneoplastic syndromes may develop:
- Polycythaemia due to erythropoietin production.
- Hypercalcaemia due to production of a parathormone-like hormone.
- The latest figures for kidney cancer patients in England and Wales report one-year relative survival to be 71.5% for men and 71.4% for women, five-year relative survival to be 53.% for men and 54.8% for women, and ten-year relative survival rates to be 43% for men and 44.4% for women.
- Patients with very early-stage kidney cancer have five-year survival rates in excess of 90%, while only around 10% of patients who present with distant metastases are alive five years later.
- There is a steady fall in survival with advancing age at diagnosis. Relative survival rates for kidney cancer patients aged under 50 are more than twice as high as for patients aged over 80.
- Indicators for a poorer prognosis for patients with metastatic RCC include low performance status, high serum lactate dehydrogenase (LDH), low haemoglobin, high serum calcium and absence of prior nephrectomy.
- If RCC recurs, it is usually within two years after surgery, with the lung being the most common site. Larger tumour diameter, T stage, stage group and nuclear grade are important factors for recurrence.
- Cigarette smoking remains the major culprit but the incidence of smoking is not rising in parallel with the number of cases of RCC.
- Obesity is increasing in Europe and the USA. Morbid obesity doubles the risk. People who are overweight but not obese are 35% more likely to develop RCC.
- Screening is currently confined to patients who have been identified as having one of the known genetic lineages linked with specific RCC subtypes.
Further reading & references
- Guidelines on Renal Cell Carcinoma; European Association of Urology (2015)
- Guidelines on Urothelial Carcinomas of the Upper Urinary Tract, European Association of Urology (2015)
- Macmillan Cancer Support
- Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up; European Society for Medical Oncology (2014)
- Guidelines on Primary Urethral Carcinoma, European Association of Urology (2015)
- UK kidney cancer statistics, Cancer Research UK
- Guidelines on Renal Cell Carcinoma, European Association of Urology (Mar 2013)
- Choyke PL, Glenn GM, Walther MM, et al; Hereditary renal cancers. Radiology. 2003 Jan;226(1):33-46.
- Cheville JC, Lohse CM, Zincke H, et al; Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol. 2003 May;27(5):612-24.
- Laparoscopic nephrectomy (including nephroureterectomy), NICE (2005)
- Laparoscopic partial nephrectomy, NICE (2006)
- Percutaneous radiofrequency ablation of renal cancer, NICE Interventional Procedure Guideline (July 2010)
- Laparoscopic cryotherapy for renal cancer, NICE Interventional Procedure Guideline (August 2011)
- Percutaneous cryotherapy for renal tumours, NICE Interventional Procedure Guideline (July 2011)
- Irreversible electroporation (IRE) for treating renal cancer, NICE Interventional procedure guideline (Feb 2013)
- Ginat DT, Saad WE, Turba UC; Transcatheter renal artery embolization: clinical applications and techniques. Tech Vasc Interv Radiol. 2009 Dec;12(4):224-39.
- Kutikov A, Egleston BL, Wong YN, et al; Evaluating overall survival and competing risks of death in patients with J Clin Oncol. 2010 Jan 10;28(2):311-7. Epub 2009 Nov 23.
- Coppin C, Le L, Porzsolt F, et al; Targeted therapy for advanced renal cell carcinoma. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006017.
- Rini BI, Campbell SC, Escudier B; Renal cell carcinoma. Lancet. 2009 Mar 28;373(9669):1119-32. Epub 2009 Mar 5.
- Sunitinib for the first-line treatment of advanced and/or metastatic renal cell carcinoma, NICE Technology Appraisal Guidance (March 2009)
- Pazopanib for the first line treatment of metastatic renal cell carcinoma, NICE Technology Appraisal Guideline (February 2011)
- Everolimus for the second-line treatment of advanced renal cell carcinoma, NICE Technology Appraisal Guideline (April 2011)
- Bevacizumab (first-line), sorafenib (first- and second-line), sunitinib (second-line) and temsirolimus (first-line) for the treatment of advanced and/or metastatic renal cell carcinoma; NICE Technology Appraisal Guidelines (August 2009)
- Volpe A, Patard JJ; Prognostic factors in renal cell carcinoma. World J Urol. 2010 Jun;28(3):319-27. doi: 10.1007/s00345-010-0540-8. Epub 2010 Apr 3.
- Chae EJ, Kim JK, Kim SH, et al; Renal cell carcinoma: analysis of postoperative recurrence patterns. Radiology. 2005 Jan;234(1):189-96. Epub 2004 Nov 10.
- Wood LS; Renal cell carcinoma: screening, diagnosis, and prognosis. Clin J Oncol Nurs. 2009 Dec;13 Suppl:3-7.
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Dr Laurence Knott
Dr Colin Tidy
Dr Hannah Gronow