Saturday, May 15, 2010

Renal cel Carcinoma:Review

The kidneys are dark-red, bean-shaped organs. There is a cavity attached to its concave side which drains into a tube which extends all the way to bladder.
Each Kidney is enclosed in a transparent membrane called the renal capsule which helps to protect them against infections and trauma. The kidney is divided into two main areas a light outer area called the renal cortex, and a darker inner area called the renal medulla. Within the medulla there are 8 or more cone-shaped sections known as renal pyramids. The areas between the pyramids are called renal columns.

Anatomy of the kidney:

What is renal cell carcinoma:
Renal cell carcinoma is the most common type of kidney cancer in adults. It occurs most often in men ages 50 - 70.
The exact cause is unknown.
Risk factors include:
• Dialysis treatment
• Family history of the disease/Genetics
• Horseshoe kidney
• Von Hippel-Lindau disease (a hereditary disease that affects the capillaries of the brain, eyes, and other body parts)
Renal cell carcimoma (RCC) is the third most common genitourinary cancer after prostate and bladder. Majority (80% to 85%) of kidney tumors are malignant. It is the most lethal malignancy of all urological cancers.
Unique characteristics of RCC
 lack of early warning signs,
 diverse clinical manifestations,
 resistance to radiation and chemotherapy, and
 immunogenic nature and spontaneous regressions.

What are the symptoms:
Now a days many renal cell carcinomas are detected incidentally during routine ultrasound examinations.
Otherwise the symptoms of renal cell carcinoma are:
Pain in flank (due to capsular distension)
Back pain
Systemic symptoms-fever,weight loss,loss of apettite
Some times it can cause paraneoplastic symptoms like-hypertension,polycythemia

Tests include:
• Abdominal CT scan: to see the size,extent and spread of the tumor

• Blood chemistry :Renal function tests
• Ultrasound of the abdomen and kidney : this is screening test
• Complete blood count (CBC): for anemia or polycythemia
• Intravenous pyelogram (IVP):Now –a days not routinely performed
• Liver function tests: staging work up
• Renal arteriography : sometimes necessary if Inferior Vena Cava spread then angioembolisation can downstage the tumor and make it less vascular and easier to operate.
• Urinalysis and urine cytology : sometimes Transitional Cell Carcinoma can mimick Renal cell Carcinoma which has different management after the initial surgery.
The following tests may be performed to see if the cancer has spread:
• Chest CT scan
• Bone scan
• MRI: especially if Inferior Vena Cava spread is suspected
• PET scan


Stage I
is an early stage of kidney cancer. The tumor measures up 7 centimeters

Stage II
is also an early stage of kidney cancer, but the tumor measures more 7 cm in size and the cancer is confined to the kidney.
Stage III is one of the following:
• The tumour has spread to adjacent renal vein or Inferior vena cava or lymph nodes
Stage IV is one of the following:
• The tumor extends beyond the fibrous tissue that surrounds the kidney(Gerotas Fascia);
• Cancer has distant spread


Radical nephrectomy remains the treatment of choice for organ confined renal cell carcinoma.
The prototypical radical nephrectomy involves removal of the cancerous kidney outside the Gerotas fascia along with the adrenal and lymphadenectomy from aortic bifurcation to crus of diaphragm.(although there are a lot controversies about the lymphadenectomy)

This can be done by Laparoscopy which uses 4 -5 ports inside the abdomen and the organ is extracted with small lower abdominal incision.Sometimes morcellation can be used to avoid the incision.
In small tumour(less than 4 cm) especially in solitary kidney or multiple tumours both the kidney a partial removal of the kidney encompassing tumour with the 5-10 mm of the normal renal parenchyma is done either by open of laparoscopic method.
When the tumor has spread to Inferior vena cava- then extensive surgery with or without cardiac bypass is needed for complete extirpation of the malignancy.
In case of unfit patients or with multiple comorbidities or multiple tumours cryo-ablation of Radio-frequency ablation can be resorted to.

Laparoscopic Cryo-ablation in process
Advanced Renal Cell Carcinoma:

RCC diagnosed early can be managed with nephron sparing or radical nephrectomy with excellent 5 year survival and prognosis. The problematic cases are those presenting as advanced disease at the initial presentation. The advanced disease includes: T4 N0 M0, or any T, any N, M1. These cases are associated with poor survival and limited treatment options.
Options for chemotherapy and endocrine-based approaches are limited, and no hormonal or chemotherapeutic regimen is accepted as a standard of care. Therefore, various biologic therapies have been evaluated. New agents, such as sorafenib and sunitinib, having anti-angiogenic effects through targeting multiple receptor kinases, and have been investigated in patients failing immunotherapy.
Role of surgery
Palliative nephrectomy should be considered in patients with metastatic disease for alleviation of symptoms such as pain, hemorrhage, malaise. Several randomized studies are now showing improved overall survival in patients presenting with metastatic kidney cancer who have nephrectomy followed by either interferon or IL-2. If the patient has good physiological status, then nephrectomy should be performed prior to immunotherapy. There are anecdotal reports documenting regression of metastatic renal cell carcinoma after removal of the primary tumor but adjuvant nephrectomy is not recommended for inducing spontaneous regression; rather, it is performed to decrease symptoms or to decrease tumor burden for subsequent therapy in carefully controlled environments.


The immune modulators, such as interferon, interleukins (IL-2, have been tried.
A : Interferons -The interferons are natural glycoproteins with antiviral, anti-proliferative, and immuno-modulatory properties. They have a direct anti-proliferative effect on renal tumor cells in vitro, stimulate host mononuclear cells, and enhance expression of major histocompatibility complex molecules.
Interferon-alpha, which is derived from leukocytes, has an objective response rate of approximately 15% (range 0-29%).
Interlukin -IL-2 is a T-cell growth factor and activator of T cells and natural killer cells. It hampers tumor growth by activating lymphoid cells in vivo without directly affecting tumor proliferation. It can be administered as high dose and low dose regimen.
A high-dose regimen (600,000-720,000 IU/kg q8h for a maximum of 14 doses) results in a 19% response rate with 5% complete responses. The majority of responses to IL-2 were durable, with median response duration of 20 months. Eighty percent of patients who responded completely to therapy with IL-2 were alive at 10 years. Most patients responded after the first cycle, and those who did not respond after the second cycle did not respond to any further treatment. Therefore, the current recommendation is to continue treatment with high-dose IL-2 to best response (up to 6 cycles) or until toxic effects become intolerable. Treatment should be discontinued after 2 cycles if the patient has had no regression.
Combinations of IL-2 and interferon or other chemotherapeutic agents such as 5-FU have not been shown to be more effective than high-dose IL-2 alone
Toxicity is dose dependent. Most common dose dependant toxicity is hypotension requiring vasopressors. Also malaise, diarrhea, pyrexia, and rashes are commonly reported toxicities.
Approved for treatment of patients with metastatic RCC.
Durability of response: Approximately 60% of CRs remain disease free at > 10 yrs follow-up
Biological Therapy:
Sunitinib (Sutent) Sunitinib is another multi-kinase inhibitor approved by the FDA in January 2006 for the treatment of metastatic kidney cancer that has progressed after a trial of immunotherapy. The approval was based on the high response rate (40% partial responses) and a median time to progression of 8.7 months and an overall survival of 16.4 months. The receptor tyrosine kinases inhibited by sunitinib include VEGFR 1-3 and PDGFR.
Major toxicities (grade II or higher) include fatigue (38%), diarrhea (24%), nausea (19%), dyspepsia (16%), stomatitis (19%), and decline in cardiac ejection fraction (11%).
A recent phase 3 study evaluating sunitinib in the first-line setting, compared against IFN-, in patients with metastatic RCC demonstrated significant improvement in PFS and response rates compared against the control arm. These results are considered to be preliminary, and longer-term follow-up is necessary for conclusive results.

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