Treatment of Stages I - III Kidney Cancer

Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 11/2021

​Stage I Renal Cancer

Patients with stage I renal cell cancer (RCC) have a primary cancer that is less than 7 centimeters in size (about 3 inches). The cancer is contained within the kidney and has not spread to lymph nodes or distant sites.

Patients with stage I renal cell cancer are curable with surgical removal of the cancer, however some cancers may effectively be managed with a "watch and wait" program of "active surveillance." During active surveillance low risk risk cancers are followed with periodic imaging studies and surgical intervention is used when the cancer shows evidence of growing.

• Learn more about "active surveillance"

Partial nephrectomy, which is removal of only the cancer and a small border of normal tissue, is the standard treatment for the smallest renal cancer (less than 4 centimeters in diameter). Depending on the size of the cancer and the function of the second kidney, some surgeons may recommend radical nephrectomy, or removal of the entire kidney. However, partial nephrectomy appears to be as effective as radical nephrectomy and preserves kidney function. Results of clinical trials have shown that 75-96% of patients with stage I renal cancers are curable with surgery alone.¹

Stage II Renal Cell Cancer

Patients with stage II renal cell cancer have a primary cancer that is larger than 7 centimeters (about 3 inches) in diameter. The cancer is limited to the kidney and has not spread to lymph nodes or distant sites.

Patients with stage II renal cell cancer are curable with surgical removal of the cancer. Radical nephrectomy, or removal of the entire affected kidney, is the standard treatment for cancers of this size. However, removal of only the cancer and a small border of normal tissue, a procedure known as a partial nephrectomy is being evaluated in the treatment of larger cancers that are surgically accessible. Results of clinical trials have shown that 63-95% of patients with stage II renal cancers are curable with surgery alone.²

Radical nephrectomy: Surgery for stage II renal cell cancer historically has involved removing the entire affected kidney and the attached adrenal gland, a procedure called a radical nephrectomy. Less invasive surgeries are being perfected and may be an option for many patients.

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, including adrenaline for coping with physical and emotional stress, corticosteroids for suppressing inflammation, and cortisol for controlling the body’s use of fats, proteins, and carbohydrates.

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.²

Stage III Renal Cell Cancer

Though stage III renal cell cancers vary in size, they share a defining feature of spread of the cancer to a single lymph node. The cancer may also have spread to nearby blood vessels—including the renal veins or vena cava—but has not spread to distant sites in the body.

Treatment for stage III renal cell cancer typically involves surgery to remove the affected kidney, affected lymph nodes, and any other cancer that may have spread near the kidney plus the attached adrenal gland and fatty tissue. This surgery is known as a radical nephrectomy. Results from clinical trials have shown that 38-70% of patients with stage III renal cell cancer are curable with surgery alone.¹ However, patients with stage III disease have cancer that has spread outside the kidney, which places them at higher risk for cancer recurrence.

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, kidney function is preserved, 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 repeatedly demonstrated in the treatment of patients with stage T1a renal cancer, which is defined a cancer that is less than 4 centimeters in diameter.^2,3

Partial nephrectomy also appears to be a viable treatment option for patients with Stage T1b cancers (which 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 are 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 are 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.

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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.⁶ 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.^6-10

Laparoscopic partial nephrectomy

appears to provide outcomes comparable to conventional open partial nephrectomy. Results of a clinical trial involving 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. Laparoscopic partial nephrectomy is a specialized technique and should only be conducted by a surgeon who is experienced in this procedure.⁸

Adjuvant Therapy

The US Food and Drug Administration has approved two adjuvant treatments for patients at high risk of recurrent RCC following nephrectomy. They initially approved the medication Sutent (sunitinib malate) based on a multi-center, clinical trial in which 615 patients with high risk RCC were treated with surgical nephrectomy and Sutent or no additional therapy. The average duration of survival without cancer recurrence for patients taking Sutent was 6.8 years compared with 5.6 years years for those receiving no additional treatment. Sutent became the first medication approved for use following surgery in high risk renal cell cancer.¹⁷

Results of a clinical trial evaluating Keytruda immunotherapy in similar patients were published in April 2021 and Keytruda was approved for use in the adjuvant setting by the FDA in November 2021.

• Adjuvant Keytruda

Strategies to Improve Treatment of Stage I-III 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 treatment of renal cell cancer include the following:

Adjuvant therapy: Cancer may recur following treatment with surgery because small amounts of cancer had already spread outside the kidney prior to the cancer’s surgical removal. It is currently estimated that 20-30% of early-stage cancers recur within three years of surgery. Recurrence most commonly occurs in the lungs.

Treatment with systemic therapy after surgery is called adjuvant therapy. Historically, adjuvant therapy with radiation therapy, chemotherapy, or immunotherapy has not been proven to be effective when administered after surgery.³ However, newer precision cancer medicines and immunotherapies being used in the treatment of metastatic renal cell cancer are now being evaluated as adjuvant therapy for patients with early-stage disease; patients should discuss the risks and benefits of participating in a clinical trial evaluating new adjuvant therapies with their physician.

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.¹¹

Cryoablation: Cryoablation is a less 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.¹²

References

1. Lam JS, Shvarts O, Pantuck AJ. Changing concepts in the surgical management of renal cell carcinoma. European Urology. 2004; 45:692-705.
2. 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.
3. 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.
4. 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.
5. 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.
6. Permpongkosol S, Chan DY, Link RE, et al. Long-term survival analysis after laparoscopic radical nephrectomy. Journal of Urology. 2005; 174:1222-1225.
7. 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.
8. Moinzadeh A, Gill IS, Finelli A, et al. Laparoscopic partial nephrectomy: 3-year followup. Journal of Urology. 2006;175(2):459-62.
9. 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.
10. Schwartz BF, Rewcastle JC, Powell T, et al. Cryoablation of small peripheral renal masses: a retrospective analysis. Urology. 2006;68(1):14-8.
11. Lam JS, Shvarts O, Pantuck AJ. Changing concepts in the surgical management of renal cell carcinoma. European Urology. 2004; 45:692-705.
12. 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.
13. Rodriguez A, Sexton WJ. Management of locally advanced renal cell carcinoma. Cancer Control. 2006;13(3):199-210.gy International. 2006;97(5):939-45.
14. Permpongkosol S, Chan DY, Link RE, et al. Long-term survival analysis after laparoscopic radical nephrectomy. Journal of Urology. 2005;174:1222-1225.
15. 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.
16. FDA approves sunitinib malate for adjuvant treatment of renal cell carcinoma