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Renal cell cancer


Table of Contents

GENERAL INFORMATION
CELLULAR CLASSIFICATION
STAGE INFORMATION
TNM definitions
AJCC stage groupings
Stage I
Stage II
Stage III
Stage IV
TREATMENT OPTION OVERVIEW
STAGE I RENAL CELL CANCER
AJCC T1 or T2, N0, M0
STAGE II RENAL CELL CANCER
AJCC TNM T3a, N0, M0
STAGE III RENAL CELL CANCER
AJCC TNM T3b, N0, M0; any T, N1-3, M0
T3b, N0, M0
any T, N1-3, M0
STAGE IV RENAL CELL CANCER
AJCC TNM T4, N0, M0; or any T, any N, M1
RECURRENT RENAL CELL CANCER

GENERAL INFORMATION

Renal cell cancer, also called renal adenocarcinoma, or hypernephroma, can often be cured if it is diagnosed and treated when still localized to the kidney and to immediately surrounding tissue. The probability of cure is directly related to the stage or degree of tumor dissemination. Even when regional lymphatics or blood vessels are involved with tumor, a significant number of patients can achieve prolonged survival and probable cure.[1] When distant metastases are present, disease-free survival is poor, although occasional selected patients will survive after surgical resection of all known tumor. Because a majority of patients are diagnosed when the tumor is still relatively localized and amenable to surgical removal, approximately 40% of all patients with renal cancer survive 5 years. Occasional patients with locally advanced or metastatic disease may exhibit indolent courses lasting several years. Late tumor recurrence many years after initial treatment occasionally occurs.

Renal cell cancer is one of the few tumors in which well-documented cases of spontaneous tumor regression in the absence of therapy exist, but this occurs very rarely and may not lead to long-term survival. Surgical resection is the mainstay of treatment of this disease. Even in patients with disseminated tumor, locoregional forms of therapy may play an important role in palliating symptoms of the primary tumor or of ectopic hormone production. Systemic therapy has demonstrated only limited effectiveness.

Separate summaries containing information on Wilms' tumor, which occurs principally in children, and transitional cell tumor of the renal pelvis and ureter are also available in PDQ.

References:

  1. Sene AP, Hunt L, McMahon RF, et al.: Renal carcinoma in patients undergoing nephrectomy: analysis of survival and prognostic factors. British Journal of Urology 70(2): 125-134, 1992.


CELLULAR CLASSIFICATION

Approximately 85% of renal cell cancers are adenocarcinomas, for the most part of proximal tubular origin. Most of the remainder are transitional cell carcinomas of the renal pelvis, which are discussed in the PDQ summary on transitional cell cancer of the renal pelvis and ureter. Adenocarcinomas may be separated into clear cell and granular cell carcinomas, although the 2 cell types may occur together in some tumors. Some investigators have found that granular cell tumors have a worse prognosis, but this finding is not universal. The distinction between well-differentiated renal adenocarcinomas and renal adenomas can be difficult. The diagnosis is usually made arbitrarily on the basis of size of the mass, but size alone should not influence the treatment approach, since metastases can occur with lesions as small as 0.5 centimeters.


STAGE INFORMATION

The staging system for renal cell cancer is based on the degree of tumor spread beyond the kidney.[1-3] Involvement of blood vessels may not be a poor prognostic sign if the tumor is otherwise confined to the substance of the kidney. Abnormal liver function test results may be due to a paraneoplastic syndrome that is reversible with tumor removal and do not necessarily represent metastatic disease. Except when computed tomography (CT) examination is equivocal or when iodinated contrast material is contraindicated, CT scanning is as good as or better than magnetic resonance imaging (MRI) for detecting renal masses.[4]

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification.[5]


TNM definitions

Primary tumor (T)

TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: Tumor 7 cm or less in greatest dimension limited to the kidney
T2: Tumor more than 7 cm in greatest dimension limited to the kidney
T3: Tumor extends into major veins or invades adrenal gland or perinephric
tissues but not beyond Gerota's fascia
T3a: Tumor invades adrenal gland or perinephric tissues but not beyond
Gerota's fascia
T3b: Tumor grossly extends into the renal vein(s) or vena cava below the
diaphragm
T3c: Tumor grossly extends into the renal vein(s) or vena cava above the
diaphragm
T4: Tumor invades beyond Gerota's fascia

Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single regional lymph node
N2: Metastasis in more than 1 regional lymph node
Note: Laterality does not affect the N classification.

Distant metastasis (M)
MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis


AJCC stage groupings


Stage I

T1, N0, M0


Stage II

T2, N0, M0


Stage III

T1, N1, M0
T2, N1, M0
T3a, N0, M0
T3a, N1, M0
T3b, N0, M0
T3b, N1, M0
T3c, N0, M0
T3c, N1, M0


Stage IV

T4, N0, M0
T4, N1, M0
Any T, N2, M0
Any T, Any N, M1

References:

  1. Bassil B, Dosoretz DE, Prout GR: Validation of tumor, nodes, metastasis classification of renal cell carcinoma. Journal of Urology 134(3): 450-454, 1985.

  2. Golimbu M, Joshi P, Sperber A, et al.: Renal cell carcinoma: survival and prognostic factors. Urology 27(4): 291-301, 1986.

  3. Robson CJ, Churchill BM, Anderson W: The results of radical nephrectomy for renal cell carcinoma. Journal of Urology 101(3): 297-301, 1969.

  4. National Institutes of Health: National Institutes of Health Consensus Development Conference: magnetic resonance imaging. Journal of the American Medical Association 259(14): 2132-2138, 1988.

  5. Kidney. In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 231-234.


TREATMENT OPTION OVERVIEW

Current treatment in renal cell cancer cures well over half the patients in stage I disease, while the results in stage IV disease are very poor. Thus, all patients with newly diagnosed renal cell cancer can appropriately be considered candidates for clinical trials when possible.


STAGE I RENAL CELL CANCER


AJCC T1 or T2, N0, M0

Surgical resection is the accepted, often curative therapy for stage I renal cell cancer. Resection may be simple or radical. The latter operation includes removal of the kidney, adrenal gland, perirenal fat, and Gerota's fascia, with or without a regional lymph node dissection. Some, but not all, surgeons believe the radical operation yields superior results. In patients who are not candidates for surgery, external radiation therapy or arterial embolization can provide palliation. In patients with bilateral stage I neoplasms (concurrent or subsequent), bilateral partial nephrectomy or unilateral partial nephrectomy with contralateral radical nephrectomy when technically feasible may be a preferred alternative to bilateral nephrectomy with dialysis or transplantation.[1] There is increasing evidence that a partial nephrectomy is curative in selected cases. It is important to have a pathologist examine the gross specimen as well as the frozen section from the parenchymal margin of excision.[2]

Treatment options:

1. Radical nephrectomy.[3]

2. Simple nephrectomy.[3]

3. Partial nephrectomy (selected patients).[1,3]

4. External-beam irradiation (palliative).[3]

5. Arterial embolization (palliative).[3,4]

6. Clinical trials.

References:

  1. Novick AC, Streem S, Montie JE, et al.: Conservative surgery for renal cell carcinoma: a single-center experience with 100 patients. Journal of Urology 141(4): 835-839, 1989.

  2. Thrasher JB, Robertson JE, Paulson DF: Expanding indications for conservative renal surgery in renal cell carcinoma. Urology 43(2): 160-168, 1994.

  3. deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45(7 Suppl): 1947-1956, 1980.

  4. Swanson DA, Wallace S, Johnson DE: The role of embolization and nephrectomy in the treatment of metastatic renal carcinoma. Urologic Clinics of North America 7(3): 719-730, 1980.


STAGE II RENAL CELL CANCER


AJCC TNM T3a, N0, M0

A surgical resection is the accepted, often curative therapy for stage II renal cell cancer. Resection should be radical. The operation includes removal of the kidney, adrenal gland, perirenal fat, and Gerota's fascia, with or without a regional lymph node dissection.[1] Lymphadenectomy is commonly employed, but its effectiveness has not been definitively proven. External-beam irradiation has been given before or after nephrectomy without conclusive evidence that this improves survival compared with results of surgery alone, but may be of benefit in selected patients with more extensive tumors. In patients who are not candidates for surgery, arterial embolization can provide palliation. In patients with bilateral stage T3a neoplasms (concurrent or subsequent), bilateral partial nephrectomy or unilateral partial nephrectomy with contralateral radical nephrectomy when technically feasible may be a preferred alternative to bilateral nephrectomy with dialysis or transplantation.[2]

Treatment options:

1. Radical nephrectomy.[3]

2. Nephrectomy before or after external-beam irradiation (selected patients).[3]

3. Partial nephrectomy (selected patients).[3]

4. External-beam irradiation (palliative).[3]

5. Arterial embolization (palliative).

6. Clinical trials.

References:

  1. Phillips E, Messing EM: Role of lymphadenectomy in the treatment of renal cell carcinoma. Urology 41(1): 9-15, 1993.

  2. Novick AC, Streem S, Montie JE, et al.: Conservative surgery for renal cell carcinoma: a single-center experience with 100 patients. Journal of Urology 141(4): 835-839, 1989.

  3. deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45(7 Suppl): 1947-1956, 1980.


STAGE III RENAL CELL CANCER


AJCC TNM T3b, N0, M0; any T, N1-3, M0


T3b, N0, M0

A surgical resection is the accepted, often curative therapy for this stage of renal cell cancer. Resection should be radical. The operation includes removal of the kidney, adrenal gland, perirenal fat, and Gerota's fascia, with or without a regional lymph node dissection. Lymphadenectomy is commonly employed, but its effectiveness has not been definitively proven. Surgery is extended to remove the entire renal vein and caval thrombus and a portion of the vena cava as necessary.[1] External-beam irradiation has been given before or after nephrectomy without conclusive evidence that this improves survival compared with results of surgery alone, but may be of benefit in selected patients with more extensive tumors. In patients who are not candidates for surgery, arterial embolization can provide palliation. In patients with stage T3b neoplasms who manifest concurrent or subsequent renal cell carcinoma in the contralateral kidney, a partial nephrectomy when technically feasible may be a preferred alternative to bilateral nephrectomy with dialysis or transplantation.[2-4]


any T, N1-3, M0

This stage of renal cell cancer is curable with surgery in a small minority of cases. A radical nephrectomy and lymph node dissection is necessary. The value of preoperative and postoperative external irradiation has not been demonstrated, but external-beam radiation therapy may be used for palliation in patients who are not candidates for surgery. Arterial embolization of the tumor with gelfoam or other materials may be employed preoperatively to reduce blood loss at nephrectomy or for palliation in patients with inoperable disease.

Treatment options:

1. For T3b tumors, radical nephrectomy with renal vein and, as necessary, vena caval resection.[1] For any T, N1-3 tumors, radical nephrectomy with lymph node dissection.

2. Preoperative embolization and radical nephrectomy.[5,6]

3. External-beam irradiation for palliation.[5]

4. Tumor embolization for palliation.[6]

5. Palliative nephrectomy.

6. Pre- or postoperative external irradiation and radical nephrectomy.[5]

7. Clinical trials involving adjuvant interferon alfa.

References:

  1. Hatcher PA, Anderson EE, Paulson DF, et al.: Surgical management and prognosis of renal cell carcinoma invading the vena cava. Journal of Urology 145(1): 20-24, 1991.

  2. deKernion JB: Management of renal adenocarcinoma. In: deKernion JB, Paulson DF, Eds.: Genitourinary Cancer Management. Philadelphia: Lea and Febiger, 1987, pp 187-217.

  3. Novick AC, Streem S, Montie JE, et al.: Conservative surgery for renal cell carcinoma: a single-center experience with 100 patients. Journal of Urology 141(4): 835-839, 1989.

  4. Angermeier KW, Novick AC, Streem SB, et al.: Nephron-sparing surgery for renal cell carcinoma with venous involvement. Journal of Urology 144(6): 1352-1355, 1990.

  5. deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45(7 Suppl): 1947-1956, 1980.

  6. Swanson DA, Wallace S, Johnson DE: The role of embolization and nephrectomy in the treatment of metastatic renal carcinoma. Urologic Clinics of North America 7(3): 719-730, 1980.


STAGE IV RENAL CELL CANCER


AJCC TNM T4, N0, M0; or any T, any N, M1

Almost all of these patients are incurable. Tumor embolization, external-beam irradiation, and nephrectomy can aid in the palliation of symptoms due to the primary tumor or related ectopic hormone production. There is minimal evidence that nephrectomy induces regression of distant metastases. Hence, nephrectomy, in the hope that it will be followed by spontaneous regression of metastases is not advised. Spontaneous regressions occasionally occur; indeed, a prospective surveillance series of 73 patients with advanced renal cell cancer demonstrated apparent temporary objective regression in 5 (7%) patients without nephrectomy or any therapy.[1] Selected patients with solitary or a limited number of distant metastases can achieve prolonged survival with nephrectomy and surgical resection of the metastases. This has been shown to be the case even for patients with brain metastases.[2] The likelihood of achieving therapeutic benefit with this approach appears enhanced in patients with a long disease-free interval between the initial nephrectomy and the development of metastatic disease.

Responses to cytotoxic chemotherapy generally do not exceed 10% for any regimen that has been studied in adequate numbers of patients. Because of early reports of success, progestational agents have been administered to patients with metastatic renal cell cancer, but the frequency of response is disappointingly low, and there is no rationale for their use as anticancer therapy. They may offer subjective palliation, however. Various biologic therapies have been evaluated. Interferon alfas have approximately a 15% objective response rate in appropriately selected individuals.[3,4] In general, these patients have non-bulky pulmonary and/or soft tissue metastases with excellent performance status (ECOG 0,1) and no weight loss. The interferon alfa doses used in studies reporting good response rates have been in an intermediate range, 6-20 MU - TIW. These responses are rarely complete or durable. More promising are treatments using interleukin-2 (IL-2).[5-8] Administration of IL-2 appears to have a similar overall response rate to interferon alfa, but with approximately 5% of the appropriately selected patients having durable complete remissions. Combinations of IL-2 and interferon have been studied but have not been shown to be better than high-dose IL-2 alone.[9] The optimum dose of IL-2 is unknown. High-dose therapy appears to be associated with higher response rates but with more toxic effects. Low-dose inpatient regimens can retain efficacy with fewer toxic effects, especially hypotension.[10] Outpatient, subcutaneous administration has also demonstrated responses with acceptable toxic effects.[11] Because of the overall poor results with drug treatment, patients with metastatic renal cell cancer should be considered for clinical trials, especially phase I and II trials evaluating newer chemotherapeutic agents and biologics such as interferons or IL-2 and strategies to modulate multidrug-resistant (MDR) phenotype, which is highly expressed in renal cell cancers.[1,3-6]

Treatment options:

1. Interleukin-2.[5-7,9,12]

2. Interferon alfa.[1,3,4]

3. External-beam irradiation (palliative).

4. Palliative nephrectomy.[13]

5. Radical nephrectomy (for T4 lesions).

6. Surgical excision of metastatic disease with radical nephrectomy (for selected M1 patients).[14]

7. Clinical trials.

References:

  1. Oliver RT, Nethersell AB, Bottomley JM: Unexplained spontaneous regression and alpha-interferon as treatment for metastatic renal carcinoma. British Journal of Urology 63(2): 128-131, 1989.

  2. Wronski M, Arbit E, Russo P, et al.: Surgical resection of brain metastases from renal cell carcinoma in 50 patients. Urology 47(2): 187-193, 1996.

  3. Krown SE: Interferon treatment of renal cell carcinoma: current status and future prospects. Cancer 59(3, Suppl): 647-651, 1987.

  4. Muss HB: The role of biological response modifiers in metastatic renal cell carcinoma. Seminars in Oncology 15(5, Suppl 5): 30-34, 1988.

  5. Rosenberg SA, Lotze MT, Muul LM, et. al.: A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and Interleukin-2 or high-dose Interleukin-2 alone. New England Journal of Medicine 316(15): 889-897, 1987.

  6. Fisher RI, Coltman CA, Doroshow JH, et al.: Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells: a phase II clinical trial. Annals of Internal Medicine 108(4): 518-523, 1988.

  7. Weiss GR, Margolin KA, Aronson FR, et al.: A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma. Journal of Clinical Oncology 10(2): 275-281, 1992.

  8. Rosenberg SA, Yang JC, Topalian SL, et al.: Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. Journal of the American Medical Association 271(12): 907-913, 1994.

  9. Atkins MB, Sparano J, Fisher RI, et al.: Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. Journal of Clinical Oncology 11(4): 661-670, 1993.

  10. Yang JC, Topalian SL, Parkinson D, et al: Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. Journal of Clinical Oncology 12(8): 1572-1576, 1994.

  11. Sleijfer DT, Janssen RA, Buter J, et al.: Phase II study of subcutaneous interleukin-2 in unselected patients with advanced renal cell cancer on an outpatient basis. Journal of Clinical Oncology 10(7): 1119-1123, 1992.

  12. 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 13(3): 688-696, 1995.

  13. deKernion JB, Berry D: The diagnosis and treatment of renal cell carcinoma. Cancer 45(7 Suppl): 1947-1956, 1980.

  14. Neves RJ, Zincke H, Taylor WF: Metastatic renal cell cancer and radical nephrectomy: identification of prognostic factors and patient survival. Journal of Urology 139(6): 1173-1176, 1988.


RECURRENT RENAL CELL CANCER

The prognosis for any treated renal cell cancer patient with progressing, recurring, or relapsing disease is poor, regardless of cell type or stage. The question and selection of further treatment depends on many factors, including prior treatment, site of recurrence, and so on, as well as individual patient considerations. Carefully selected patients may benefit from surgical resection of localized metastatic disease, particularly if they have had prolonged disease-free interval since primary therapy.

Responses to cytotoxic chemotherapy generally do not exceed 10% for any regimen that has been studied in adequate numbers of patients. Because of early reports of success, progestational agents have been administered to patients with metastatic renal cell cancer, but the frequency of response is disappointingly low, and there is no rationale for their use as anticancer therapy. They may offer subjective palliation, however. Various biologic therapies have been evaluated. Interferon alfas have approximately a 15% objective response rate in appropriately selected individuals.[1,2] In general, these patients have non-bulky pulmonary and/or soft tissue metastases with excellent performance status (ECOG 0,1) and no weight loss. The interferon alfa doses used in studies reporting good response rates have been in an intermediate range, 6-20 MU daily - TIW. These responses are rarely complete or durable. More promising are treatments using interleukin-2 (IL-2).[3-6] Administration of IL-2, with or without lymphokine-activated killer (LAK) lymphocytes, appears to have a similar overall response rate to interferon alfa, but with approximately 5% of the appropriately selected patients having durable complete remissions. Combinations of IL-2 and interferon have been studied but have not been shown to be better than high-dose IL-2 alone.[7] Low-dose inpatient regimens can retain efficacy with fewer toxic effects, especially hypotension.[8] Outpatient, subcutaneous administration has also demonstrated responses with acceptable toxic effects.[9] Because of the overall poor results with drug treatment, patients with metastatic renal cell cancer should be considered for clinical trials, especially phase I and II trials evaluating newer chemotherapeutic agents and biologics such as interferons or IL-2.[1-4]

Treatment options:

1. Interleukin-2.[3-5,7,10,11]

2. Interferon alfa.[1,2]

3. External-beam irradiation (palliative).

4. Vinblastine.

References:

  1. Krown SE: Interferon treatment of renal cell carcinoma: current status and future prospects. Cancer 59(3, Suppl): 647-651, 1987.

  2. Muss HB: The role of biological response modifiers in metastatic renal cell carcinoma. Seminars in Oncology 15(5, Suppl 5): 30-34, 1988.

  3. Rosenberg SA, Lotze MT, Muul LM, et. al.: A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and Interleukin-2 or high-dose Interleukin-2 alone. New England Journal of Medicine 316(15): 889-897, 1987.

  4. Fisher RI, Coltman CA, Doroshow JH, et al.: Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells: a phase II clinical trial. Annals of Internal Medicine 108(4): 518-523, 1988.

  5. Weiss GR, Margolin KA, Aronson FR, et al.: A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma. Journal of Clinical Oncology 10(2): 275-281, 1992.

  6. Rosenberg SA, Yang JC, Topalian SL, et al.: Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. Journal of the American Medical Association 271(12): 907-913, 1994.

  7. Atkins MB, Sparano J, Fisher RI, et al.: Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. Journal of Clinical Oncology 11(4): 661-670, 1993.

  8. Yang JC, Topalian SL, Parkinson D, et al: Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report. Journal of Clinical Oncology 12(8): 1572-1576, 1994.

  9. Sleijfer DT, Janssen RA, Buter J, et al.: Phase II study of subcutaneous interleukin-2 in unselected patients with advanced renal cell cancer on an outpatient basis. Journal of Clinical Oncology 10(7): 1119-1123, 1992.

  10. Belldegrun A, Abi-Aad AS, Figlin RA, et al.: Renal cell carcinoma: basic biology and current approaches to therapy. Seminars in Oncology 18(5): 96-101, 1991.

  11. 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 13(3): 688-696, 1995.

Date Last Modified: 04/1999



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