Kidney Cancer Information
What is Kidney Cancer?
Types of Kidney Cancer
Kidney cancer is not one disease but consists of several types of cancers. Renal cell carcinoma (RCC) originates in the tubules of the kidney and comprises 90% of what people refer to as kidney cancer. Transitional cell carcinoma (TCC) occurs outside the kidney in the area that drains the urine leading to the bladder (the ureter). Its pathology more resembles bladder cancer than RCC. Renal sarcoma originates in the connective tissue of the kidney and is much rarer than RCC. Wilms’ tumor is a childhood form of kidney cancer.
Finally, oncocytomas are benign tumors originating in the kidney. They can turn cancerous and are currently treated as if they are malignant tumors, that is, they are removed surgically or ablated (see below). There is no attempt to distinguish oncocytomas from malignant tumors when they are found in the kidney.
Renal cell cancers are usually distinguished by their pathology, or the appearance of the kidney cancer cells under the microscope.
Clear cell kidney cancer occurs in about 80% of the cases. It’s called clear cell because the cells appear mostly clear under the microscope. Papillary renal cell cancer occurs in about 15% of the cases. Chromophobe occurs in about 5%, and collecting duct occurs in fewer than 1% of the cases.
Papillary and chromophobe are slow-growing cancers, and if caught early, may be cured by surgical removal of the cancer. But neither papillary nor chromophobe has any non-experimental medical treatment beyond surgery. Clear cell is faster growing, but it benefits from the fact that most of the medical treatments focus on this variety. Collecting duct is very aggressive and has no known treatment beyond surgery.
Kidney Cancer Symptoms
In its early stage, kidney cancer usually does not show any symptoms and is often diagnosed incidentally when the patient undergoes a procedure such as a CT scan for another problem. When it metastasizes, kidney cancer can have a range of symptoms. The following symptoms have been reported by kidney cancer patients.
- Pain in the side or the back above the lumbar region that persists (note that many people report a pain in their back, which usually emanates from muscle or disk injuries and is unrelated to kidney cancer)
- A lump in the abdomen area
- Blood in the urine
In some of the cases, the kidney cancer can cause other systemic disturbances not directly related to the primary tumor, such as night sweats, recurrent fever, weight loss, high blood pressure, anemia, elevated blood sedimentation rate, abnormal liver enzymes, etc.
Kidney cancer is diagnosed at an average age of 54. It is about twice as prevalent in men as in women. If you experience any of the above symptoms and are above the age of 50, you should ask your doctor for an ultrasound (sonogram) of the abdominal and pelvic areas. This is an inexpensive screening test and can diagnose kidney as well as other solid tumor cancers such as bladder and ovarian. If you have a family history of cancer, kidney or otherwise, you should also have periodic sonograms taken.
Screening & Diagnosis
For healthy individuals undergoing a normal medical exam, there is currently no screening test such as a blood or urine test, available for kidney cancer. For first-time diagnosis of kidney cancer and for follow-up tests for kidney cancer patients, radiological tests are required. Biopsies of tumors in the kidney are usually not performed because the biopsy may miss the tumor and for fear that the cancer cells may be spread by the procedure.
An ultrasound test is inexpensive, non-invasive, emits no radiation and is very efficient in diagnosing kidney cancers that are limited to the kidney. Since ultrasound can help diagnose primary tumors in other internal organs as well as kidney, in some countries like Japan, ultrasounds are part of the regular annual check-ups.
For primary diagnosis, when something is seen in the kidney by an ultrasound test, medical practitioners usually follow up with a CT scan (computed tomography) to make a more definitive diagnosis. A CT scan can be given with or without contrast, that is, with a dye that can highlight the areas under investigation. The CT scan with contrast is the more efficient procedure.
The gold standard of diagnostic tools is the MRI, which gives a more extensive view of not only the kidney but also the surrounding areas including the renal artery and vein, the ureter, etc, but can give too much information and may be more difficult to interpret for a non-radiologist. For primary diagnosis, the MRI can be used as a follow-up to an ultrasound and or CT scan.
For first time diagnosis, an ultrasound is sufficient. It is non-invasive and is inexpensive with less than half the cost of a CT scan. The equipment is less expensive and can even be found in some doctors’ offices. It emits no radiation so is safe for pregnant women. A CT scan and an MRI must be done in a radiology lab.
For follow-up and for primary diagnosis, either the CT scan with contrast or the MRI can be used, the latter being more expensive.
Treatment of Kidney Cancer
The first-line treatment for kidney cancer is surgery, that is, the removal of the entire affected kidney (simple nephrectomy), removing only the diseased area of the kidney (partial nephrectomy), or removing the kidney and the surrounding lymph nodes and/or adrenal gland (radical nephrectomy). A partial nephrectomy leaves the patient with more kidney function, but its feasibility depends upon the size and placement of the tumor.
Nephrectomies can be done either through open surgery or laparoscopically, the latter being less invasive.
Other methods that preserve the kidney in addition to a partial nephrectomy involve tumor ablation, or destroying the tumor in place. The variants are: cryoablation (freezing the tumor) and radiofrequency ablation (burning it via ultrasound or laser beams). These ablation techniques are used where the tumor is small and well-placed, the patient cannot undergo major surgery due to age or physical condition, and/or where preserving kidney function is critical. Since this is a fairly new technique, there are no long term studies, e.g. 10 years, to ascertain whether the technique successfully obliterates the entire tumor preventing future return of the cancer in the same kidney.
Treatment of metastatic kidney cancer
For more than ten years, the standard medical treatment for metastatic kidney cancer has been immunotherapy agents such as Interleukin-2 (IL-2) and Interferon. IL-2 was approved by the Federal Drug Administration (FDA) for treatment of kidney cancer in 1992. All other medical treatments are off-label drugs, that is, they are approved by the FDA for treatment of other types of cancer but can, upon justification by the prescribing physician, be used for kdieny cancer patients as well.
High dose IL-2, administered intravenously, has a 20-25% short-term response rate, that is, tumor shrinkage, but only a 5-10% complete response rate, or remission of the disease. Long-term, durable complete response (say over 5 years), or total disappearance of any lesions, has averaged about 5%. High dose IL-2 is toxic and must be administered on a hospital in-patient basis to monitor the side effects, which can be severe, although they are usually all reversible. Low dose IL-2 can be administered sub-cutaneously at home or intravenously as well and the side effects are less severe that those for high dose. However, the results have not been as effective either. Finally, IL-2 has also been prescribed for use with an inhalator for metastatic patients with lung lesions. But its use has been mostly limited to Europe. IL-2 is only effect for patients with clear cell histology. Another immunotherapy drug that has been used to fight kidney cancer is Interferon-_ (alpha). It is sometimes used in combination with low dose IL-2 but has not proved to be as effective as high-dose IL-2.
Little progress has been made with immunotherapy drugs since IL-2 was introduced. Most of the studies now involve tumor shrinking or anti-angiogenesis drugs. Angiogenesis is the process whereby new blood vessels are grown in the body, a natural phenomenon for all cells but a critical one for tumor cells. Since tumors require blood vessel growth in the tumor area, inhibitors to that growth can impede the spread of the cancer. These new investigational drugs, such as sutent and sorafenib, are called targeted therapies, since, in order to inhibit certain processes, they target specific proteins of the body rather than acting on the whole body itself as immunotherapy agents do.
These new drugs must go through the clinical trial process in order to be approved. Entry into clinical trials is restrictive and depends on the stage of the cancer, any previous treatment the patient has received, and the overall health of the patient. See www.cancer.gov/clinicaltrials for a listing of current trials.
In addition to medical treatment, surgery, radiation, and chemotherapy may be options for metastasized kidney cancer. If a single metastasis can be completely excised, the odds of complete cure increase dramatically.
It is important to be aware, the since kidney cancer is actually more than one disease, the recommended treatment for metastatic disease and the patient’s prognosis will depend on the pathology, the extent, size and location of the metastatic nodules, and the overall health of the patient.
By law, a prescription drug cannot be marketed until it has been proven to be both safe and effective. The Food and Drug Administration (FDA) oversees the clinical trial process, which was established in the early 1960s to provide evidence for FDA approval of new drugs. There are three basic phases to the clinical trial process, as follows.
- Phase I Trials: The function of a phase I trial is to test the safety of the drug, that is, what dosage can be administered to the patient while keeping the side effects within a tolerable range. An ancillary function is to note the efficacy of the drug. Patients should not expect to derive personal benefits from being on a phase I trial, but the results will benefit people who enter subsequent trials.
- Phase II Trials: Once a safe dosage is established, a drug is tested for efficacy, that is, measuring the tumor(s) response to the drug – do they shrink, grow, or remain stable. The investigator usually sets an a priori objective for the trial such as “time to progression” or the time during which a patient is taking the drug before which the tumors start growing again.
- Phase III Trials: Once the safety and efficacy of the drug are established, the drug is tested in an expanded trial setting involving more patients. This is the last step before FDA approval so a drug company will often test the drug either against another drug that is standard treatment for the disease or against a placebo. This is called patient randomization whereby patients are distributed among two or more arms of a trial where each arm receives a different course of treatment.There is dispute over the ethics of holding placebo trials for cancer trials. In some placebo trials there is crossover, that is, when patients are on the placebo arm of a trial and the tumors start growing again, these patients are then given the investigative drug in place of the placebo.
- Phase IV Trials: After a drug has FDA approval for a specific disease, a pharmaceutical company may conduct a trial to obtain approval for the drug for a different disease or even for the same disease using a different formulation of the drug. The FDA may also ask a drug company to run an additional trial to test for a particular side effect of the drug. To date, phase IV trials have not been conducted for kidney cancer drugs.
Follow-up after initial treatment
After nephrectomy, current medical practice is to still use radiological tests to see if the cancer has returned. For normal follow-up for a non-metastatic tumor, the recommended course is for a CT scan of the chest area, without contrast, and either a CT scan with non-ionic contrast or an MRI of the pelvic and abdomen areas. The CT scan should be sufficient, however, the dye used for contrast can have a deleterious effect on the kidneys so if one suffers from kidney disease, an MRI is recommended.
In general, an MRI is superior to a CT scan with contrast for the following reasons:
- It is more extensive giving superior views to CT scans for which other axial cuts would be necessary, that is, one would have to know what they’re looking for before giving the procedure.
- There is no radiation with an MRI as there is with a CT scan.
- As mentioned, the CT scan uses a dye that can have a negative effect on the remaining kidney especially if the patient’s creatinine level is high. The MRI’s dye has no effect on the kidney.
The downsides of an MRI are the cost and the training required to be able to read the scans. Radiologists usually have the required training, but many oncologists may not be as experienced in reading the results. Further, if patients have metallic objects embedded in their bodies, such as pacemakers, MRIs would not be called for.
Finally, the CT scan is superior to an x-ray, yielding results of higher definition and exhibiting less dispersal of the radiation.
Kidney Cancer Staging
Once diagnosed and treated, oncologists categorize the kidney cancer into stages, which, among other things, leads to a prognosis for recovery.
- Stage I: Consists of cancers where the tumor is entirely encapsulated within the kidney and measures less than 7 cm in diameter at its widest part.
- Stage II: Similar to Stage 1, except that the tumor is larger than 7 cm in diameter.
- Stage III: The cancer has spread to one or more lymph nodes or an adrenal gland, or it has invaded the renal vein or vena cava (the large vein, located outside the kidney, which returns the blood to the heart).
- Stage IV: The cancer has spread to a distant organ.
If kidney cancer metastasizes it usually spreads to the lungs, liver, brain, or bones. If someone has metastasized kidney cancer in the lungs, for example, they still have kidney cancer. It is not lung cancer.
If the cancer is limited to the kidney, the 5-year survival rate is estimated as 90%. If it is found in a local lymph node, the survival rate drops to 60%. If it has spread to a distant organ, the 5-year survival rate is 9%. The overall survival rate for someone with kidney cancer averages 63%.
Another factor in survival prediction is the grade of the tumor, or what the cells’ nuclei look like. Grade varies from 1 to 4, with grade 4 being the most aggressive. For a more extensive treatment of kidney cancer basics, refer to Steve Dunn’s Cancer Guide at www.cancerguide.org.
Risk Factors Associated with Kidney Cancer
The following may increase the risk of developing kidney cancer.
- family history of kidney cancer
- genetic predisposition, that is, either inheriting or developing at birth a genetic mutation that includes von Hippel Lindau disease and Birt Hogg Dubé syndrome
- over-use of diuretics and of analgesics that contain phenacetin (banned in 1987)
- long-term dialysis and long-term history of kidney stones and cystic disease
- exposure to certain toxic chemicals such as trichloroethylene (an industrial solvent), perchlorethylene (used in dry cleaning), cadmium (used in battery mfg, etc), asbestos and benzene
After initial treatment for cancer, medical treatments are applied to try and prevent the cancer from recurring. This treatment is called adjuvant therapy. For example, for breast cancer, Tamoxifen or other drugs are administered to prevent the return of the cancer. For kidney cancer, there is no proven adjuvant therapy although there are experimental trials for vaccines.
Note that kidney cancer can recur many years after the initial diagnosis and treatment. Thus someone may be “cancer free” for 10 or 20 years and then have a recurrence of the kidney cancer. Scientists and oncologists do not understand the mechanism that causes this recurrence.
For more information about kidney cancer, refer tot he National Cancer Institute’s publication “What You Need to Know about Kidney Cancer” which can be found on-line at http://www.cancer.gov/cancerinfo/wyntk/kidney or can be ordered at https://cissecure.nci.nih.gov/ncipubs/details.asp?pid=122.
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