Treatment for renal cell cancer is tailored to each individual and may include surgery, precision cancer medicines, immunotherapy and/or chemotherapy. Radiation therapy is not typically used for the treatment of renal cell cancer. The specific treatment depends on the stage and genomic profile of the cancer.
Surgery. Patients with early stage renal cell cancer are curable with surgical removal of the cancer. Partial nephrectomy, which is removal of only the cancer and a small border of normal tissue, is the standard treatment for the smallest cancers however patients will require a radical nephrectomy, or removal of the entire kidney for larger renal cell cancers.1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20
Systemic Therapy: Precision Cancer Medicine, Chemotherapy, and Immunotherapy
Systemic therapy is any treatment directed at destroying cancer cells throughout the body. Some patients with early stage cancer already have small amounts of cancer that have spread outside the kidney. These cancer cells cannot be treated with surgery alone and require systemic treatment to decrease the chance of cancer recurrence. More advanced cancers that cannot be treated with surgery can only be treated with systemic therapy. Systemic therapies commonly used in the treatment of renal cell cancer include:
Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs. Chemotherapy drugs cannot tell the difference between a cancer cell and a healthy cell. Therefore, chemotherapy often affects the body’s normal tissues and organs, which can result in complications or side effects. In order to more specifically target the cancer and avoid unwanted side effects researchers are increasingly using precision cancer medicines.
Precision Cancer Medicines
Through genomic-biomarker testing performed on a biopsy of the cancer or from a blood sample doctors are increasingly able to define the genomic alterations in a cancers DNA that are driving the growth of a specific cancer. Once a genetic abnormality is identified, a precision medicine can be designed to target a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed. Precision medicines have been developed for the treatment of RCC with identifiable cancer driving mutations.21,22,23
Precision immunotherapy treatment of cancer has also progressed considerably over the past few decades and has now become a standard treatment. The immune system is a network of cells, tissues, and biologic substances that defend the body against viruses, bacteria, and cancer. The immune system recognizes cancer cells as foreign and can eliminate them or keep them in check up to a point. Cancer cells are very good at finding ways to avoid immune destruction, however, so the goal of immunotherapy is to help the immune system eliminate cancer cells by either activating the immune system directly or inhibiting the mechanisms of suppression of the cancer.
Researchers are mainly focused on two promising types of immunotherapy. One type creates a new, individualized treatment for each patient by removing some of the person’s immune cells, altering them genetically to kill cancer, and then infusing them back into the bloodstream the other uses precision medications to enhance the immune systems response to the cancer.
Immunotherapy can also work by more broadly stimulating the immune system to fight the cancer. Historically the most frequently used types of immunotherapy to treat RCC were Proleukin® (interleukin-2) and alfa interferon, however newer precision cancer immunotherapy drugs called “checkpoint inhibitors” are able to more precisely activate the immune system with fewer side effects.21,22,23
Treatment of Renal Cell Cancer by Stage
Staging is ultimately confirmed by surgical removal of the cancer and exploration of the area adjacent to the kidney. The following are simplified definitions of the various stages of renal cell cancer. Click on a stage for an overview of the most recent information available concerning the comprehensive treatment.
Stage I: The primary cancer is 7 centimeters (about 3 inches) or less and is limited to the kidney, with no spread to lymph nodes or distant sites.
Stage II: The primary cancer is greater than 7 centimeters (about 3 inches) and is limited to the kidney, with no spread to lymph nodes or distant sites.
Stage III: The cancer has spread to the regional lymph nodes but not to distant sites in the body, and/or extends to the renal veins or vena cava (large vein returning blood to the heart located in the middle of the abdomen near the back).
Stage IV: The cancer has spread to distant sites or invades directly beyond the local area.
Recurrent Renal Cell Cancer: Renal cell cancer has returned after primary treatment.
Surgery for Renal Cell Cancer
Surgery is the mainstay of treatment for renal cell cancers (RCC), a type of cancer that is typically resistant to radiation and chemotherapy. Surgery is almost always utilized unless patients are unable to tolerate the procedure.
Historically, surgical treatment of RCC consisted of a radical nephrectomy, which involves removal of the entire kidney, local lymph nodes, and any cancer in the area surrounding the kidney. The trend in the surgical management of RCC however, is to perform less aggressive surgery when possible. Less aggressive surgery, which removes only the part of the kidney affected with cancer, is referred to as a partial nephrectomy or nephron-sparing surgery.
In patients with Stage I and II renal cell cancer, surgery can cure the majority of patients; 75-96% of patients with Stage I disease and 63-95% of patients with Stage II disease are cured with surgery alone. Surgery can be curative for Stage III renal cancer depending on the extent of disease, but the percentage of patients with this stage who are cured with surgery alone drops to 38-70%.5 Surgical removal of some metastatic cancers can also be curative. Surgery can also relieve symptoms caused by the cancer in patients with Stage III and IV renal cell cancer and in those with recurrent disease.
There are several surgical approaches that are utilized, depending on the extent of disease and the condition of the patient.
Partial Nephrectomy (Nephron-Sparing Surgery)
Removing only the cancer and some surrounding healthy tissue—a procedure called a partial nephrectomy—is now considered the standard of care for the treatment of smaller cancers. The benefits of this approach are shorter hospitalization and recovery time and, importantly, kidney function is preserved; preservation of kidney function is particularly valuable for patients who already have poor function or only one kidney. Preserving the affected kidney is also valuable in the event that the cancer should recur in the opposite (contralateral) kidney.
Partial nephrectomy also appears to be a viable treatment option for patients with stage T1b cancers (cancers that are 4-7 centimeters in diameter) if an adequate amount of normal tissue surrounding the cancer can be removed.4 Patients with these slightly larger stage I cancers who were treated with partial nephrectomy have been shown to live as long and experience a similar cancer-free duration as patients treated with radical nephrectomy.5 However, longer follow up aimed at confirming these findings is ongoing.
For those patients with stage T1b cancer that is more centrally located or those with multiple tumors, radical nephrectomy may be a better option.
Surgery for stage II renal cell cancer typically involves removing the entire affected kidney, local lymph nodes, and the attached adrenal gland, a procedure called a radical nephrectomy.
In some cases, the adrenal gland may not need to be removed. The adrenal glands are complex organs that work with the brain to produce and regulate important hormones.
Researchers have reported that patients who underwent nephrectomy but did not have the adrenal gland removed survived as long as patients who underwent nephrectomy with removal of the adrenal gland and were not at any higher risk of postoperative complications.6
Surgery to Remove Metastases
Some patients can experience long-term cancer-free survival after surgical resection of metastatic cancers. Results of a clinical trial indicate that renal cell cancer that has spread to the lungs can be removed with surgery. Patients treated with surgery for lung metastases but no evidence of cancer elsewhere in the body, including the kidney, nearly 40% survived five years or more. Patients with only a single site of cancer in the lung experienced the best outcomes; nearly 50% survived five years or more compared to 19% of patients who had more than one site of cancer removed.7
Strategies to Improve Surgical Treatment of Renal Cell Cancer
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Areas of active investigation aimed at improving the surgical treatment of renal cell cancer include the following:
- Partial Nephrectomy (Nephron-Sparing Surgery)
- Laparoscopic surgery
- Radiofrequency ablation
Partial Nephrectomy (Nephron-Sparing Surgery): Removing only the cancer and some surrounding healthy tissue—a procedure called a partial nephrectomy—is now considered the standard of care for the treatment of small renal cancers. The benefits of this approach are shorter hospitalization and recovery time and, importantly, preservation of kidney function, which is particularly valuable for patients who already have poor function or only one kidney. Preserving the affected kidney is also valuable in the event that the cancer should recur in the opposite (contralateral) kidney. The benefits and safety of this approach have been demonstrated8,9,10,11 in stage I cancers, and some research is ongoing to determine if any patients with stage III renal cancers may also benefit from partial nephrectomy.
Laparoscopic surgery: Laparoscopic surgery is a technique that is less extensive and invasive than traditional, open surgery. During a laparoscopic surgery for renal cancer, the surgeon makes small, one-centimeter incisions in the abdomen and side. The surgeon then inserts a very small tube that holds a video camera, which creates a live picture of the inside of the patient’s body. This picture is continually displayed on a television screen, so that surgeons can perform the entire surgery by watching the screen.
Both radical nephrectomy and partial nephrectomy may be conducted using laparoscopy. In the case of a radical nephrectomy, the incision is enlarged to allow passage of the kidney. A small bulk of tissue is removed with a partial nephrectomy and the incision can remain small.
Laparoscopic radical nephrectomy has emerged as an alternative to open surgery in the management of smaller (less than 8 centimeters in diameter), localized renal cancers. Patients treated with the laparoscopic approach do not appear to be at greater risk for cancer recurrence 5-10 years after treatment compared to patients treated open radical nephrectomy. The two approaches have also been shown to result in similar survival.12 However, patients who are candidates for laparoscopic radical nephrectomy would also do well with partial nephrectomy. The advantages of laparoscopic radical nephrectomy (shorter hospital stay and faster recovery) must be balanced with the advantage of partial nephrectomy, which is better long-term renal function.13
Laparoscopic partial nephrectomy appears to provide outcomes comparable to conventional open partial nephrectomy. Results of a clinical trial that evaluated 100 patients with an average cancer size of 3.1 cm who underwent laparoscopic surgery showed that all patients survived three and one-half years or more after treatment without evidence of cancer recurrence.14 Laparoscopic partial nephrectomy is a specialized technique and should only be conducted by a surgeon who is experienced in this procedure.
Radiofrequency ablation: Radiofrequency ablation is a minimally invasive technique that uses heat to destroy cancer cells. During radiofrequency-ablation, an electrode is placed directly into the cancer under the guidance of a CT scan, ultrasound, or laparoscopy. The electrode emits high frequency radio waves, creating intense heat that destroys the cancer cells.
Radiofrequency ablation appears to be a promising technique for the treatment of patients with small kidney cancers (less than 4 centimeters in diameter) who are ineligible for surgery. Clinical trial results indicate that two years after surgery, cancer recurrence occurred in fewer than 10% of patients. Larger tumors (more than 3 centimeters) are more challenging to treat with this approach and are more prone to recurrence afterwards.15
Cryoablation: Cryoablation is a minimally invasive technique that uses extremely cold temperatures to “freeze” small cancers. In patients with cancer that is less than or equal to 5.0 cm in diameter, cryoablation appears to be a promising approach for removing the cancer. However, long-term research is necessary to confirm the benefits of cryoablation.16
Radiation therapy uses high-energy radiation to kill cancer cells. External beam radiation therapy uses radiation delivered from outside the body that is focused on the cancer. Radiation therapy is sometimes used as the main treatment for kidney cancer for patients whose general health is too poor to undergo surgery. Radiation therapy can also be used to temporarily palliate or ease symptoms of kidney cancer such as pain, bleeding or problems caused by metastasis. Unfortunately, renal cell cancer is not very sensitive to radiation and while the growth of cancer can be slowed, it cannot be entirely eliminated.
Currently, the use of radiation therapy before or after removing the cancer is not routinely recommended because clinical studies have not shown any improvement in patient outcomes.
Side effects of radiation therapy may include mild skin changes (similar to sunburn), nausea, diarrhea, or tiredness. Often these go away after a short time. Chest radiation therapy may cause lung damage and lead to difficulty breathing and shortness of breath. Side effects of brain radiation therapy usually become most serious one or two years after treatment and can include headache and difficulty thinking.
1 Flanigan RC, Salmon SE, Blumenstein BA et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. New England Journal of Medicine. 2001; 345:1655-9.
2 Fyfe G, Fisher RI, Rosenberg SA, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. Journal of Clinical Oncology. 1995;13(3):688-696.
5 Lam JS, Shvarts O, Pantuck AJ. Changing concepts in the surgical management of renal cell carcinoma. European Urology. 2004; 45:692-705.
6 Joniau S, Vander Eeckt K, Van Poppel H. The indications for partial nephrectomy in the treatment of renal cell carcinoma. Nature Clinical Practice Urology. 2006;3(4):198-205.
7 Becker F, Siemer S, Humke U, et al. Elective nephron sparing surgery should become standard treatment for small unilateral renal cell carcinoma: Long-term survival data of 216 patients. European Urology. 2006;49(2):308-13.
8 Leibovich BC, Blute ML, Cheville JC, et al. Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy. Journal of Urology. 2004;171(3):1066-70.
9 Dash A, Vickers AJ, Schachter LR, et al. Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma of 4-7 cm. British Journal of Urology International.2006;97(5):939-45.
10 Siemer S, Lehmann J, Kamradt J, et al. Adrenal metastases in 1635 patients with renal cell carcinoma: outcome and indication for adrenalectomy. Journal of Urology. 2004;171(6 Pt 1):2155-9.
11 Friedel G, Hurtgen M, Penzenstadler M, et al. Resection of pulmonary metastases from renal cell carcinoma. Anticancer Research. 1999;19(2C):1593-1596.
12 Joniau S, Vander Eeckt K, Van Poppel H. The indications for partial nephrectomy in the treatment of renal cell carcinoma. Nature Clinical Practice Urology. 2006;3(4):198-205.
13 Becker F, Siemer S, Humke U, et al. Elective nephron sparing surgery should become standard treatment for small unilateral renal cell carcinoma: Long-term survival data of 216 patients. European Urology. 2006;49(2):308-13.
14 Leibovich BC, Blute ML, Cheville JC, et al. Nephron sparing surgery for appropriately selected renal cell carcinoma between 4 and 7 cm results in outcome similar to radical nephrectomy. Journal of Urology. 2004;171(3):1066-70.
15 Dash A, Vickers AJ, Schachter LR, et al. Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma of 4-7 cm. British Journal of Urology International. 2006;97(5):939-45.
16 Permpongkosol S, Chan DY, Link RE, et al. Long-term survival analysis after laparoscopic radical nephrectomy. Journal of Urology. 2005; 174:1222-1225.
17 Matin SF, Gill IS, Worley S, et al. Outcome of laparoscopic radical and open partial nephrectomy for the sporadic 4 cm. or less renal tumor with a normal contralateral kidney. Journal of Urology. 2002;168(4 Pt 1):1356-9.
18 Moinzadeh A, Gill IS, Finelli A, et al. Laparoscopic partial nephrectomy: 3-year followup. Journal of Urology. 2006;175(2):459-62.
19 Varkarakis IO, Allaf ME, Takeshi I, et al. Percutaneous radio frequency ablation of renal masses: results at a 2-year mean followup. Journal of Urology. 2005; 174:456-460.
20 Schwartz BF, Rewcastle JC, Powell T, et al. Cryoablation of small peripheral renal masses: a retrospective analysis. Urology. 2006;68(1):14-8.
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