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  • This manual is not a substitute for consultation with an appropriate specialist.
  • The contents of this manual have been developed through consensus of a Provincial Tumour Group. Please note the various update dates for each section as some of the content of the manual may not be up to date.

1. Predisposing Factors/Prevention

Updated 3 July 2007

The incidence of renal cancer is relatively high in B.C. at 11.7/100,000 in males and 7.4/100,000 in females.

Cigarette smoking increases risk of renal cell carcinoma (RCC) as well as cancers of the renal pelvis and ureter although the relative risk even in heavy smokers is modest at about two-fold (McLaughlin et al 1996). Use of several drugs appears to increase risk of all kidney cancers. These drugs include phenacetin containing compounds and diuretics. However since diuretics are commonly used by hypertensives, further study is necessary to evaluate whether high blood pressure rather than use of diuretics might contribute to the elevated risk. Obesity, in particular in females, also seems to be associated with a higher risk.

Several inherited forms of renal cell carcinoma have been described. The most common inherited RCC syndrome is the von Hippel-Lindau (VHL) disease, which is characterized by a germ-line mutation in the VHL gene and predisposition to angiomas, CNS hemangioblastomas, pheochromocytomas and clear-cell RCCs. Other hereditary forms of RCC include hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis and renal cell cancer (HLRCC), the Birt-Hogg-Dubé syndrome (BHD), familial clear cell carcinomas with a constitutional chromosome 3 translocation as well as a non-syndromic familial clear cell RCC.


Elimination of cigarette smoking appears to be the most promising way to reduce the incidence of kidney cancer. No screening or early detection manoeuvres are available at present.


  1. McLaughlin JK, Blot W, Devesa S, Fraumeni JF Jr. Renal cancer. In Schottenfeld D, Fraumeni JF Jr. (Eds) Cancer Epidemiology and Prevention ; 1996. Oxford University Press, Oxford. Pp 1142-1155.

2. Screening/Early Detection

Updated 3 July 2007

Rarely, renal cell carcinoma (RCC) occurs in a familial form as described above and up to 45% of patients with von Hippel-Lindau syndrome will develop renal cell carcinoma. The familial syndromes are associated with renal cell carcinoma in younger age groups and disease may be bilateral. The occurrence of RCC at young age should prompt a thorough family history and a referral to an expert center. Annual ultrasound screening for patients with hereditary syndromes is recommended.

Although renal cell carcinoma is more common in smokers and patients with autosomal dominant polycystic kidney disease, screening has not been shown to be effective for these risk groups.

3. Diagnosis

​Updated 3 July 2007

Clinico-pathologic Considerations

Most renal tumours in adults are renal cell carcinomas, and discussion elsewhere refers to this histologic type. However it is essential not to overlook the possibility of a more treatable histology in a younger patient or where any atypical clinical features are present. These unusual tumours include:

  1. Transitional cell carcinomas of renal pelvis
  2. Lymphomas (see Lymphoma section of this manual)
  3. Sarcomas (consider referral to Sarcoma service)
  4. Adult Wilms' tumour

These tumours require individualized management.

Radical Nephrectomy Specimens Should Include the Following Information:

Gross Description

  1. The size of the kidney (three dimensions)
  2. The length of attached ureter
  3. The size of any tumour mass and the size of any satellite nodules
  4. The location of any tumour masses
  5. The relationship to capsule, to the renal pelvis and to the renal vessels
  6. The presence of tumour within the renal vein

Microscopic Description

  1. Histologic classification:
    clear cell carcinoma
    papillary carcinoma
    chromophobe carcinoma
  2. Presence or absence of vascular invasion
  3. The invasion of capsule, renal pelvis, perirenal fat
  4. The status of all resection margins
  5. Lymph nodes status
  6. Fuhrman nuclear grade (1 - Well, 2-3 - Moderate, 4 - Poor)

4. Staging

Updated 28 June 2007

Classification Criteria

TXPrimary tumour cannot be assessed
T0No evidence of primary tumour
T1aTumour 4 cm or less in greatest dimension, limited to the kidney
T1bTumour greater than 4 cm, but not more than 7 cm, in greatest dimension, limited to the kidney
T2Tumour more than 7.0 cm in greatest dimension, limited to the kidney
T3aTumour invades adrenal gland or perinephric tissues but not beyond Gerota's fascia
T3bTumour grossly extends into renal vein(s) or vena cava below diaphragm
T3cTumour grossly extends into vena cava above diaphragm
T4Tumour invades beyond Gerota's fascia
 The regional lymph nodes are the hilar, abdominal para-aortic, and para caval nodes. Laterality does not affect the N categories
NXRegional lymph nodes cannot be assessed
N0No regional lymph node metastasis
N1Metastasis in a single regional lymph node
N2Metastasis in more than one regional lymph node
*Laterality does not affect the N classification
NOTEIf a lymph node dissection is performed, then pathologic evaluation would ordinarily include at least eight nodes
 Including extraregional lymph nodes
MXDistant metastasis cannot be assessed
M0No distant metastasis
M1Distant metastasis
VXVenous invasion cannot be assessed
V0Veins do not contain tumour
V1Renal vein contains tumour
V2Vena cava contains tumour
GRADE(Fuhrman Nuclear Grade – ref: Am J Surg Pathol 6:655-663, 1982)
1Tumour composed of cells with small (approx. 10µ) round uniform nuclei with inconspicuous or absent nucleoli
2Tumour composed of cells with larger (approx. 15µ) nuclei which exhibited irregularities in outline and nucleoli when examined under high (400x)power
3Tumour composed of cells with large nuclei (approx.20µ) with an obviously irregular outline and prominent large nuclei even at low (100x) power
4Tumour composed of features similar to grade 3 with the addition of bizarre, often multilobed nuclei and heavy chromatin clumps. These tumours often had areas of spindled-shaped cells resembling sarcomas
XUnknown/not assessed

Staging Diagram

Kidney staging diagram

Investigations for Staging

2002 TNM staging system recommended (see above).When surgery is considered, it is assumed that the patient will have been fully investigated to rule out metastatic disease.

The investigations should include:

  1. History and physical examination
  2. CBC, liver function tests, BUN, creatinine, calcium
  3. Chest X-ray
  4. Intravenous pyelogram
  5. CT scan abdomen
  6. Bone scan
  7. CT brain (if suspect symptoms present)
  8. Angiograms (for selected cases)

5. Management

Updated 28 October 2008

Stage I (T1 N0 M0) and Stage II (T2 N0 M0)

Radical nephrectomy with or without regional node dissection.

Partial nephrectomy in select cases of functional solitary kidneys or small polar lesions.

Stage III (T1 N1 M0 - T2 N1 M0 - T3 N0,N1 M0)


Radical nephrectomy with or without regional node dissection. Renal vein or vena cava involvement can be surgically evacuated with curative intent. Patients with bilateral primary renal cell carcinoma or only one functioning kidney may undergo partial nephrectomy.

Radiation Therapy

Radiation therapy has no established role as primary definitive therapy of early renal cancers or as an adjuvant to surgery (preoperative or postoperative).


Chemotherapy has no role as adjuvant therapy for high risk tumours.

Stage IV (T4 N0 N1 M0 - any T N2 M0 - any T any N any M1) or Recurrent Disease

Surgery - Current Policy

  1. Palliative nephrectomy or angioinfarction may be required for uncontrolled pain and bleeding
  2. Palliative nephrectomy is recommended in combination with interferon for patients in good performance status. This policy is based on two parallel randomized studies with a weighted median survival improvement of approximately six months. These trials selected only the fittest patients and therefore only such patients should be considered for up-front nephrectomy
  3. The role of palliative nephrectomy in combination with Vascular endothelial growth factor (VEGF) receptor inhibitors is currently unknown. However, based on the eligibility criteria of the pivotal phase III trial as well as retrospective data, cytoreductive nephrectomy is recommended in patients with good performance status (ECOG 0,1). An interval of at least three weeks is currently recommended between major surgery and the initiation of anti-angiogenic therapy
  4. Resection of a solitary metastasis or oligo-metastases in a single site, from renal cell carcinoma should be considered for patients in good performance status if the patients has synchronous limited metastatic spread, or if the interval from nephrectomy to the detection of metachronous limited metastases is sufficiently long and the metastatic site is proven to be solitary by adequate restaging (CT of brain, chest and abdomen, bone scan)


Tannock IF. Commentary on "cytoreduction nephrectomy in metastatic renal cancer: the results of SWOG 8949". J Clin Oncol 2000; 18(21 Suppl):39S-42S.

Radiation Therapy

Radiation therapy may be used to control bleeding and pain from the primary tumour and to palliate symptoms from metastases.

Chemotherapy and Immunotherapy

  • Chemotherapy, such as vinblastine or other chemotherapy agents, is not recommended
  • Interferon-alpha has proven superiority over medroxyprogesterone acetate within a randomized trial in patients with metastatic RCC. Interferon-alpha provides response rates of 6-15% resulting in a modest survival benefit of three to four months. Single patients with long term survival have been reported. Only good prognosis patients appear to benefit, so generally, only highly selected RCC patients with good prognosis features should be considered for interferon. This includes patients with clear cell histology, good performance status, a progression-free interval following initial diagnosis of more than one year and preferably lung metastases as the sole metastatic site
  • Other cytokines such as interleukin or cytokine combinations such as interferon plus interleukin have not shown significant benefit in randomized trials or have not been validated compared to best supportive care in randomized trials
  • Patients that have had nephrectomy with a good disease-free interval and are found to have asymptomatic recurrence (e.g. small lung metastases) may also be observed without treatment. Such a period of observation can be very prolonged in selected patients. This allows a better knowledge of the tempo of the disease and is associated with a better quality-of-life than any of the systemic treatments. This appears to be a safe alternative to immediately starting treatment as long as patients remain under close observation. Treatment should be initiated upon progression.
  • Small molecule tyrosine kinase inhibitors against VEGF are considered the new reference standard of care in RCC with clear cell component.
  • Sorafenib: a tyrosine kinase inhibitor with activity against Raf kinases, VEGFR-2, and PDGFR. Sorafenib has shown to significantly improve progression-free survival as second-line therapy in patients with metastatic RCC after cytokine failure (HR 0.44).
    Sorafenib is recommended for patients after cytokine failure.
    Although there was no difference in progression-free survival, Sorafenib was associated with better tolerability, less side effects, fewer kidney cancer related symptoms and higher quality of life as compared to interferon within a randomized phase II study in previously untreated patients with advanced RCC.
    Sorafenib may therefore also be considered as an alternative to sunitinib as first-line therapy if patients are unsuitable for sunitinib
  • Sunitinib: a small molecule tyrosine kinase inhibitor with activity against VEGFR, PDGFR, KIT and FLT-3. Sunitinib has demonstrated an objective response rate of approximately 40% and a tumour control rate (CR+PR+SD ≥ 3 months) of approximately 70% as second-line therapy after cytokine failure in two large phase II studies. Sunitinib can therefore serve as an alternative to sorafenib as second-line therapy after cytokine failure.
    A large randomized trial comparing Sunitinib with interferon as first-line therapy including 747 patients with metastatic RCC showed a progression-free survival of 11 months versus 5 months in favour of Sunitinib. Most patients had good or intermediate risk criteria according to the Motzer criteria. Sunitinib is the reference standard for first-line therapy in patients with metastatic RCC
  • Temsirolimus: an inhibitor of the mammalian target of rapamycin (mTOR). Within a large randomized phase III trial, Temsirolimus proved to be significantly superior over Interferon with regards to both progression-free and overall survival in patients with poor prognosis metastatic RCC based on the modified Motzer criteria. Temsirolimus should be considered for patients with metastatic poor risk RCC
  • The role of second line therapy after failure of anti-angiogenesis agents is currently unknown and is being investigated in clinical trials


  1. Escudier B., Eisen T., Stadler W. et al: Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma. N Engl J Med 356:125-34, 2007

  2. Motzer R., Rini B., Buzkowski R. et al: Sunitinib in Patients With Metastatic Renal Cell Carcinoma. JAMA 295:2516-2524, 2006

  3. Motzer R., Michelson D., Redman B. et al: Activity of SU11248, a Multitargeted Inhibitor of Vascular Endothelial Growth Factor Receptor and Platelet-Derived Growth Factor Receptor, in Patients With Metastatic Renal Cell Carcinoma. J Clin Oncol 24:16-24, 2006

  4. Motzer R., Hutson T., Tomczak P. et al: Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma. N Engl J Med 356:115-24, 2007

  5. Hudes G., Carducci M., Tomczak P et al: Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271-2281, 2007

  6. Szczylik C., Demkow T., Staehler M., Rolland F., Negrier S., Hutson TE., Bukowski RM, Scheuring UJ., Burk K., Escudier B.: Randomized phase II trial of first-line treatment with sorafenib versus interferon in patients with advanced renal cell carcinoma: Final results. J Clin Oncol ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement): 5025, 2007


Updated 3 July 2007​

Post Nephrectomy

Although asymptomatic recurrence is usually incurable, a small chance does exist that a solitary metastasis could be treated definitively. Follow up is through the urologist and/or the family doctor and it is important for the patient to be clear who is responsible.

  • Years 1 + 2 = q 6 months
  • Year 3+ = annually

(Chest X-ray should be performed at each visit and ultrasound of contralateral kidney is recommended on alternate years for early detection of a second primary).

Following the completion of treatment, all patients need to be monitored for potential recurrence of cancer and complications of therapy. This is needed both for management of the individual patient (where early detection would improve outcome), and to permit periodic review and improvement of current treatment policy.

Often it is felt appropriate to share follow up with the family doctor (and/or the urologist), in which case it is important for the patient to be clear who is responsible for certain aspects of the disease, e.g. symptom control by the family doctor, with advice from the BC Cancer Agency at the doctor's request.

Notification is requested in the event of any of the following:

  1. Local recurrence at the primary site (particularly in patients with clinically localized disease treated with surgery and/or radiotherapy)
  2. Metastasis at regional or distant sites
  3. Complications of therapy especially if acute requiring hospitalization, or chronic and symptomatic
  4. Death with primary cause and whether cancer or treatment contributed

The event, date, and evidence where appropriate should be sent to the Agency chart where it will come to the attention of the oncologist, and will be available for periodic review by the tumour group. This information is requested annually for patients no longer followed at the BC Cancer Agency.

SOURCE: Kidney ( )
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