Our knowledge of cancer is always expanding. Researchers and healthcare professionals take the knowledge gained from research studies and use it to develop better practices that will help prevent, detect and treat kidney cancer, as well as improve the quality of life of people with kidney cancer.
The following information is a selection of research showing promise for kidney cancer.
Diagnosis
A key area of research activity involves developing better ways to diagnose and stage kidney cancer.
Noteworthy research includes:
- Researchers are investigating gene expression profiling and protein microarray technologies as tools to diagnose cancer. Microarrays allow scientists to quickly and accurately analyze many genes at one time using specialized equipment. Current techniques cannot always reliably tell the difference between cancerous (malignant) and non-cancerous (benign) kidney tumours. Gene expression profiling trials are currently underway and may one day help to both diagnose and tailor treatment for kidney cancers (Diagnostic Molecular Pathology, PMID* 22089348; ASCO**, Abstract 405).
- Researchers are studying positron emission tomography (PET) to see if it is a useful imaging technique for finding kidney cancer. PET/CT scanning combines computed tomography (CT) and PET into one procedure. PET/CT is showing promise for staging kidney cancer. It may also be helpful in monitoring a person’s response to treatment or finding cancer that has come back after treatment. Further studies are needed to confirm the benefit of PET/CT (European Journal of Radiology, PMID 20015602; BJU International, PMID 19007371).
Prognostic factors
Prognostic factors that may help determine the outcome of the disease are being studied in kidney cancer. They can be used to predict the chances of recovery or of cancer coming back. Doctors may also use prognostic factors to help them make treatment recommendations.
Noteworthy research includes:
- Researchers have found that people with kidney cancer who smoke or have a history ofsmoking have a worse prognosis than people who have never smoked. People who smoke tend to have more lung and heart problems and a worse performance status than those who don’t smoke (ASCO, Abstract 4578).
- Researchers have shown that tumour size is helpful in predicting prognosis for people with kidney cancer. People with small kidney tumours have a better prognosis than those with tumours that are larger than 7 cm (Journal of Urology, PMID 19084868).
- Recent research has shown that age and gender may be related to prognosis for kidney cancer.
- A large Asian study found that women with kidney cancer tend to have lower stage and lower grade tumours compared to males with kidney cancer. Younger women, however, tended to have higher grade, higher stage tumours with unfavourable cell characteristics compared to men of a similar age (International Journal of Urology, PMID 19456990).
- Korean researchers found that women with kidney cancer had better rates of survival than men. Women had lower rates of clear cell renal cell carcinoma (RCC) and higher rates of chromophobe RCC, which are favourable prognostic factors (BJU International, PMID 22085161).
- Another study found that people 45 years ofageand younger diagnosed with kidney cancer have a more favourable prognosis than people who are diagnosed at an older age. Cancer tends to come back more often in people older than 60 years of age than in younger people (Urology, PMID 21256565; Journal of Urology, PMID 19524959).
- There is some evidence that surgery for cancer surgery, including partial and radical nephrectomy, may be associated with more negative effects of treatment (higher morbidity) than previously thought. Elderly people appear to have the highest morbidity associated with surgery (Journal of Urology, PMID 21788042).
- In addition to stage, researchers recently looked at the expression of Ki-67 (a biomarker indicating cell growth) and the presence of cancer cells within blood vessels (microvascular invasion) in kidney tumours. People whose tumours tested positive for Ki-67 and who had cancer cells present in blood vessels were considered to have a less favourable prognosis (BJU International, PMID 19388989).
- C-reactive protein(CRP) is a protein found in the blood. When there is tissue inflammation, CRP levels rise. Studies have found that people with kidney cancer who have high levels of CRP measured in the blood or in the tumour after it has been removed may have a less favourable prognosis (ASCO, Abstract 333; Journal of Urology, PMID 21849188, PMID 20006861).
- Cyclin dependent kinase 1 (CDK1) and CDK2 are proteins that control cell division. Researchers measured CDK1 and CDK2 levels in tumours from people with renal cell carcinoma. Low levels of CDK1 and CDK2 were associated with a more favourable prognosis (ASCO, Abstract 341).
- Gene expression profiling may help doctors predict tumour behaviour and identify people with kidney cancer who may have a better or worse prognosis. Being able to identify different prognostic groups for kidney cancer will help doctors choose appropriate treatments. Furthermore, genes may be used as biomarkers that could potentially help to develop new treatments for kidney cancer (Lancet Oncology, PMID 22015057; Journal of Urology, PMID 21600596; ASCO, Abstract 4556, Abstract 338, Abstract 405). This research requires tumour samples. Researchers are testing the following genes to see if they may be helpful in tailoring drug treatment and improving prognosis in people with kidney cancer:
- vascular endothelial growth factor receptor (VEGFR)
- cytochrome P450 3A5 (CYP3A5)
- PET scans may also be helpful in determining prognosis in people with advanced kidney cancer. People whose tumours showed high uptake levels of the radiopharmaceutical used in PET scanning had a less favourable prognosis (BMC Cancer, PMID 21129184).
Treatment
Researchers are looking for new ways to improve the treatment of kidney cancer. Advances in cancer treatment and new ways to manage the side effects related to treatment have improved the outlook and quality of life for many people with cancer.
Noteworthy research for localized disease (cancer within the kidney) includes:
- A large study looked at the outcome of people with kidney cancer who had the entire kidney removed (radical nephrectomy) compared to those who only had part of the kidney removed (partial nephrectomy). Those who had a partial nephrectomy tended to have better overall survival and a lower risk of heart problems associated with death (Journal of Urology, PMID 21849201). There is some evidence that surgery for cancer surgery, including partial and radical nephrectomy, may be associated with more negative effects of treatment (higher morbidity) than previously thought. Elderly people appear to have the highest morbidity associated with surgery (Journal of Urology, PMID 21788042).
- Robotic surgery has evolved from laparoscopic surgery and other minimally invasive surgical techniques. The surgeon uses a computer to move instruments connected to robotic arms. The operation is done through several small incisions. Researchers are using robotic surgery to remove part of the kidney (partial nephrectomy) to see if it is a better way to perform surgery for kidney cancer. Research has shown that robotic surgery can result in less pain after surgery, quicker recovery, shorter hospital stays and less scarring (BJU International, PMID 21917097, PMID 21917094; Urology, PMID 21333338).
- Some doctors are using cryosurgery (cryoablation) as an alternative to removing part or all of the kidney (partial or radical nephrectomy) for small tumours (2–5 cm) that have not spread outside the kidney. Cryosurgery may be performed by inserting a probe through the skin with the help of a computed tomography (CT) scan (percutaneous method), or with a laparoscope guided by ultrasound (Journal of Urology, PMID 20719341; Urology, PMID 20579705; Current Opinion in Oncology, PMID 19188767).
- Long-term follow-up of people who have undergone cryosurgery showed that, of those who had not died of causes unrelated to cancer, 83% were still alive after 10 years (Journal of Urology, PMID 20089263).
- Research has shown that both percutaneous and laparoscopic methods are effective in treating small kidney tumours. The percutaneous method appears to be associated with fewer complications and shorter hospital stays than the laparoscopic method. However, a recent study found that while both techniques were effective in treating small kidney tumours, the laparoscopic method had a higher rate of success with the first treatment attempt (Journal of Endourology, PMID 19456244).
- A recent study found that people who were treated with cryosurgery had good kidney function 2 years following treatment (Journal of Endourology, PMID 19839780).
- Radiofrequency ablation (RFA) uses a special needle-thin probe to direct high-frequency current that heats and destroys abnormal tissue. RFA may be used as an alternative to partial or radical nephrectomy in some people with kidney cancer (Urology, PMID 21492910; Acta Radiologica, PMID 20707665; Cancer, PMID 20564644; BJU International, PMID 19426196; European Journal of Radiology, PMID 19181470; Journal of Endourology, PMID 19118475). Studies are looking at RFA as a treatment for:
- small kidney tumours (2–5 cm) that have not spread outside the kidney
- kidney tumours that cannot be removed by surgery
- people with kidney cancer who are not well enough to have surgery
- people with kidney cancer who only have one kidney
- Microwave ablation is a technique similar to radiofrequency ablation that uses microwaves to destroy tumours. The doctor uses ultrasound to guide a probe that delivers microwaves to the tumour. Several probes can be used to treat different parts of a tumour if it is larger than 2 cm. Researchers are studying microwave ablation as an alternative treatment option for people who cannot undergo surgery for kidney cancer (Journal of Endourology, PMID 20932080; Cardiovascular and Interventional Radiology, PMID 19915901).
- High-intensity focused ultrasound (HIFU) is a minimally invasive procedure that focuses ultrasound waves to create intense heat, which destroys tissue. Researchers are studying HIFU as an alternative to surgery in people with small kidney tumours (BJU International, PMID 21929519, PMID 20230379).
Noteworthy research in treatment given before (neoadjuvant therapy) or after (adjuvant therapy) surgery for people with kidney cancer includes:
- In the last 5 years, targeted therapies that block new blood vessel formation (angiogenesis), or other pathways within cells that promote tumour growth, have become the standard of care in advanced disease. Researchers are now evaluating whether giving these drugs either before surgery (neoadjuvant therapy) in an attempt to shrink tumours or after surgery (adjuvant therapy) will help to reduce the risk of the kidney cancer coming back. People who may be eligible to participate in a clinical trial will often be asked to join the trial before or after surgery. They will need to agree to be randomly assigned to observation (current standard of care) or to get the drug being tested. People who are considered low risk for recurrence of kidney cancer are usually excluded from these trials to avoid possibly harming them with the trial drug or diluting the trial drug and missing its possible benefit. It is important to check with the surgeon to see if there are any open trials that the person could participate in. Researchers are also trying to better understand what factors may help predict who will or will not respond to targeted therapy, and who will or will not experience toxicity.
- Adjuvant therapy:
- Researchers are studying whether giving the angiogenesis inhibitor drugs sunitinib (Sutent) or sorafenib (Nexavar) after surgery is better or worse than giving no treatment (placebo) to people who have had their kidney removed. This international study has now completed accrual, which means it has finished enrolling participants. The participants are currently being followed to see how they respond to these drugs (NCI Clinical Trial***, Protocol ID NCT00326898).
- Another trial in the United Kingdom is comparing sorafenib to placebo to see whether sorafenib may help prevent cancer from coming back in people who are considered high risk for recurrence. This study is currently recruiting participants (NCI Clinical Trial, Protocol ID NCT00492258).
- An international trial is comparing sunitinib to placebo to see whether sunitinib may help prevent cancer from coming back in people who are considered high risk for recurrence. This study is currently recruiting participants (NCI Clinical Trial, Protocol ID NCT00375674).
- Everolimos (Afinitor) is a targeted therapy approved for treating metastatic clear cell types of kidney cancer, after they stop responding to sunitinib and sorafenib. A phase III trial is also studying everolimos against a placebo to see if it can help to prevent recurrence in people who have been treated with surgery (NCI Clinical Trial, Protocol ID NCT01120249).
- Pazopanib (Votrient) is a newer angiogenesis inhibitor recently approved for treating metastatic clear cell types of kidney cancer. Pazopanib is also being studied in a phase III trial against a placebo to see if it can help to prevent recurrence in people who have had their kidney removed (NCI Clinical Trial, Protocol ID NCT01235962).
- Researchers are studying the value of molecular testing in determining prognosis. By looking for molecular targets in individual tumours, it may be possible to tailor the best targeted drug treatment for each person at relapse or even as adjuvant therapy after nephrectomy. Molecular testing will be compared to results of treatment or placebo to see if this method of testing is helpful in determining prognosis in people with kidney cancer.
- Neoadjuvant therapy:
- There is emerging evidence that giving targeted treatment to shrink tumours before surgery (neoadjuvant therapy) may also be beneficial. A few early studies have reported that it is possible to successfully shrink tumours. Neoadjuvant therapy to shrink tumours before surgery is not yet considered standard of care, so further research is needed and clinical trials are ongoing. Neoadjuvant therapy clinical trials collect tissue at the time of biopsy and then after treatment, which allows researchers to study the tumour at the microscopic level and learn what effect the targeted treatment has. Studies are ongoing to determine the safety of giving targeted treatments before surgery.
- More research is still needed to determine how neoadjuvant therapy may benefit people with metastatic kidney cancer. There is some evidence that giving neoadjuvant therapy before surgery may be associated with problems after surgery (post-operative complications). A study found that the majority of people receiving neoadjuvant therapy before surgery had a post-operative complication, such as wound separation and infection (ASCO, Abstract 300).
Noteworthy research for advanced and metastatic kidney cancer includes:
- In addition to sorafenib and sunitinib, the targeted therapy drugs temsirolimus (Torisel), everolimos (Afinitor) and pazopanib (Votrient) have been approved in Canada to treat metastatic kidney cancer. When given to treat metastatic kidney cancer, these drugs are used in a slightly different way than when they are used as adjuvant therapy (described above). Many ongoing clinical trials are fine-tuning how these drugs are used. Other targeted therapy drugs that are being tested to treat metastatic kidney cancer include the following:
- Axitinib (AG-013736) is a tyrosine kinase inhibitor (TKI) that blocks chemicals called tyrosine kinases. These chemicals are part of the signalling process within cells. When this process is blocked, the cell stops growing and dividing. Researchers are studying axitinib as a treatment for metastatic kidney cancer in people who do not respond to other targeted therapy treatments. A phase III study compared axitinib to sorafenib for the second-line treatment of metastatic kidney cancer. Those who received axitinib had longer progression-free survival (the time it takes for the cancer to start growing again after treatment) rates than those who were given sorafenib (Lancet, PMID 22056247).
- Tivozanib (AV-951) is a vascular endothelial growth factor receptor (VEGFR) inhibitor that controls blood vessel development (an anti-angiogenesis drug). Tivozanib has shown promising results in a phase II study and will soon be tested in a phase III clinical trial (ASCO, Abstract 4599). The phase III study will compare tivozanib and sorafenib in people with advanced kidney cancer (ASCO, Abstract 310; NCI Clinical Trial, Protocol ID NCT01030783).
- A large Canadian study analyzed several clinical trials that used targeted therapy to treat metastatic kidney cancer. The individual trials found that sunitinib, bevacizumab (Avastin) and temsirolimus resulted in improved progression-free survival compared to interferon alfa (Intron A, Wellferon). After analyzing these clinical trials, the Canadian researchers found that sunitinib was a better treatment than either sorafenib or bevacizumab plus interferon alfa because sunitinib resulted in longer progression-free survival. No differences in progression-free survival were found between sorafenib or bevacizumab plus interferon alfa or sorafenib and bevacizumab alone (BMC Cancer, PMID 19173737). The drawback of this study is that it did not directly compare these drugs in the same clinical setting.
- Canadian researchers have shown that progression-free survival at 3 months and at 6 months predicted overall survival in people with metastatic kidney cancer who received targeted therapy. This means that whether or not the disease progresses at the 3 or 6 month point during treatment may help predict how well a person with metastatic kidney cancer will do overall. Those whose cancer progressed at 3 and 6 months had a shorter overall survival than those whose cancer did not progress until a later point in time (Cancer, PMID 21656741).
- In addition to looking for new drugs, clinical trials for metastatic kidney cancer are looking into the best order for giving existing useful drugs, and whether there is benefit to combining drugs. It is sometimes difficult to give drugs in combination because overlapping side effects may mean that the amount of each drug given needs to be lowered. Kidney cancer is not very common, so people are encouraged to participate in research when there is an opportunity. Clinical trials are excellent opportunities to improve the current standards of care. In many cases, clinical trials allow a person with cancer access to promising drugs, such as the many targeted therapy drugs currently in development.
- A large review of records from people with kidney cancer confirmed that radical nephrectomy to remove a cancerous kidney greatly improved survival rates for people with locally advanced or stage IV kidney cancer whose tumours had grown through Gerota’s fascia but had not spread to nearby lymph nodes. The Canadian researchers also found that radical nephrectomy did not improve survival rates for people who had cancer that had spread to nearby lymph nodes (BJU International, PMID 19389018). This is still controversial data as other studies have not drawn the same conclusions. More research is needed to determine the best use of surgery in advanced kidney cancer.
- In people who have metastatic kidney cancer, researchers are trying to find out if it is beneficial to remove the kidney (nephrectomy) before giving targeted drug therapy (as was shown previously for interferon alfa).
- Canadian and American researchers found that people with metastatic renal cell carcinoma who had a nephrectomy before receiving targeted therapy survived longer than those only given targeted therapy. There was less benefit in having nephrectomy before targeted therapy in people who belonged to the poor prognostic risk group (Journal of Urology, PMID 21074201). This study reviewed past cases where not all relevant data was available.
- Clinical trials are planned to further our understanding of the benefit of nephrectomy before targeted therapy. These trials are designed to find out whether people with metastatic kidney cancer should have their kidney removed before they receive targeted therapy (NCI Clinical Trial, Protocol ID NCT01099423; NCI Clinical Trial, Protocol ID NCT00930033).
- A Canadian study showed that sorafenib given before surgery was well-tolerated and shrank the tumour within the kidney. Also, neoadjuvant sorafenib did not result in extra complications following surgery in people with metastatic kidney cancer. In this study, neoadjuvant therapy allowed a surgeon to remove the kidney, which can help control the symptoms of advanced kidney cancer (ASCO, Abstract 4668).
- Giving temsirolimus (Torisel) before radical nephrectomy may be a treatment option for people with advanced kidney cancer. Canadian researchers found this treatment may be helpful for removing a significant amount of the cancer in the body (ASCO, Abstract 387).
- Researchers are studying stereotactic radiosurgery as a treatment option for metastatic kidney tumours that have spread to the brain or spine. Some studies have shown that this exact method of delivering radiation therapy can control brain metastases (World Neurosurgery, PMID 20860956). Gamma Knife surgery is a type of stereotactic radiosurgery that uses gamma radiation to treat cancer. Gamma Knife surgery may be used to treat single or multiple metastatic brain tumours (ASCO, Abstract e15071; Neurosurgery, PMID 21716155, PMID 19165071; Journal of Neuro-oncology, PMID 20405309).
Supportive care
Living with cancer can be challenging in many different ways. Supportive care can help people cope with cancer, its treatment and possible side effects.
Noteworthy research includes:
- Bisphosphonates may be given to people with metastatic kidney cancer that has spread to the bones. Bisphosphonates help prevent bone breakdown and strengthen bones. A study has reported that people with metastatic kidney cancer who take sunitinib and bisphosphonates have a greater likelihood of developing osteonecrosis of the jaw. Osteonecrosis is the death of bone due to reduced blood supply. Osteonecrosis of the jaw bone underneath the teeth is a side effect of some bisphosphonates, but the combination of bisphosphonates and sunitinib appears to further increase the risk of osteonecrosis of the jaw. For this reason, people may be advised to see a dentist regularly to check for any problems (ASCO, Abstract e15021, Abstract e15116).
*PMID is the National Library of Medicine PubMed abstract identity number.
**ASCO is the American Society of Clinical Oncology.
***NCI is the National Cancer Institute.
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