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Clinical Management of Renal Tumors pp 293–306Cite as

Adjuvant Therapy of Renal Cell Carcinoma

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Abstract

A series of adjuvant studies are reviewed that have been conducted in patients with localized renal cell carcinoma following nephrectomy. The randomized studies available do not demonstrate an advantage for pre- or postoperative therapy. Patient selection criteria have varied, but generally high risk groups with T2–4 tumors and lymph node metastases (N+) disease have been included. In the future, adjuvant trials conducted in this group of patients must take into account histology, as well as selection of patients by pathologic stage. Trail design is of importance and randomized studies in which a control population is included are required. The issue of placebo controls will depend upon the agent utilized and its toxicity. External review of radiologic data will be of importance to validate results if a surrogate endpoint such as disease free survival is utilized. In view of our current knowledge of the biology of clear cell carcinoma, studies utiling medications such as sunitinib, sorafenib, or bevacizumab are considerations.

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References

  1. Bloom HJG. Adjuvant therapy for adenocarcinoma of the kidney: present position and prospects. Br J Urol 1973;45:237–257.

    Article  PubMed  CAS  Google Scholar 

  2. Linehan WM, Shipley WV, Parkinson D. Cancer of the kidney and ureter. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. Philadelphia: Lippincott-Raven, 1997:1271–1299.

    Google Scholar 

  3. Rabinovitch RA, Zelefsky MJ, Fuks Z. Patterns of failure following surgical resection of renal cell carcinoma: implications for adjuvant local and systemic therapy. J Clin Oncol 1994;11:206–212.

    Google Scholar 

  4. Zisman A, Pantuck AJ, Dorey F, et al. Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol 2001;19:1649–1957.

    PubMed  CAS  Google Scholar 

  5. Patard J, Kim HL, Lam JS, et al. Use of the University of California Los Angeles Integrated Staging System to predict survival in renal cell carcinoma: an international multicenter study. J Clin Oncol 2004;22:3316–3322.

    Article  PubMed  Google Scholar 

  6. Bui MHT, Visapaa H, Seligson D, et al. Prognostic value of carbonic anhydrase IX and Ki67 as predictors of survival for renal clear cell carcinoma. J Urol 2004;171:2461–2455.

    Article  PubMed  Google Scholar 

  7. Seligson DB, Pantuck A, Liu X, et al. Epithelial cell adhesions molecule (KSA) expression: pathobiology and its role as an independent predictor of survival in renal cell carcinoma. Clin Can Res 2004;10:2659–2669.

    Article  CAS  Google Scholar 

  8. Kattan MW, Reuter V, Motzer RJ, Katz J, Russo P. A postoperative prognostic monogram for renal cell carcinoma. J Urol 2001;166:63–67.

    Article  PubMed  CAS  Google Scholar 

  9. Zisman A, Pantuck AJ, Dorey F, et al. Mathematical model to predict individual survival for patients with renal cell carcinoma. J Clin Oncol 2002;20:1368–1374.

    Article  PubMed  Google Scholar 

  10. Robson CJ, Churchill BM, Anderson W. The results of radical nephrectomy for renal cell carcinoma. J Urol 1969;101(3):297–301.

    PubMed  CAS  Google Scholar 

  11. Gunan P, Sobon LH, Algaba F, et al. TNM staging of renal cell carcinoma: wordgroup No. 3—Union International Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer 1997;80:992–993.

    Article  Google Scholar 

  12. Bloom HJG. Medroxyprogesterone acetate (Provera) in the treatment of metastatic renal cancer. Br J Cancer 1971;25:250–256.

    PubMed  CAS  Google Scholar 

  13. Henriksson R, Nilsson S, Colleen S, et al. Survival in renal cell carcinoma—a randomized evaluation of tamoxifen vs interleukin 2, α-interferon (leukocyte) and tamoxifen. Br J Cancer 1998;77:1311–1317.

    PubMed  CAS  Google Scholar 

  14. Medical Research Council Renal Cancer Collaborators. Interferon-α and survival in metastatic renal cell carcinoma: early results of a randomized control trial. Lancet 1999;353:14–17.

    Article  Google Scholar 

  15. Satomi Y, Takai S, Kondo I, Fukushima S, Furuhata A. Postoperative prophylactic use of progesterone in renal cell carcinoma. J Urol 1982;128:919–922.

    PubMed  CAS  Google Scholar 

  16. Pizzocaro G, Piva L, DiFonzo G, et al. Adjuvant medroxyprogesterone acetate to radical nephrectomy in renal cancer: 5-year results of a prospective randomized study. J Urol 138 1987;138:1379–1381.

    CAS  Google Scholar 

  17. Peeling WB, Mantell BS, Shepheard BCF. Postoperative irradiation in the treatment of renal cell carcinoma. Br J Urol 1969;41:23–31.

    Article  PubMed  CAS  Google Scholar 

  18. Cox CE, Lacy SS, Montgomery WG, Boyce WH. Renal adenocarcinoma: 28-year review, with emphasis on rationale and feasibility of preoperative radiotherapy. J Urol 1970;104:53–61.

    PubMed  CAS  Google Scholar 

  19. Rafla S. Renal cell carcinoma. Natural history and results of treatment. Cancer 1970;25:26–40.

    Article  PubMed  CAS  Google Scholar 

  20. Aref I, Bociek RG, Salhani D. Is postoperative radiation for renal cell carcinoma justified: Radiother Oncol 1997;43:155–157.

    Article  PubMed  CAS  Google Scholar 

  21. van der Werf-Messing B. Carcinoma of the kidney. Cancer 1973;32:1056–1061.

    Article  PubMed  Google Scholar 

  22. Juusela H, Malmio K, Afthan O, Oravisto J. Preoperative irradiation in the treatment of renal adenocarcinoma. Scand J Urol Nephrol 1977;11:277–281.

    Article  PubMed  CAS  Google Scholar 

  23. Kjaer M, Frederiksen PL, Emgelholm SA. Postoperative radiotherapy in stage II and III renal adenocarcinoma. A randomized trial by the Copenhagen renal cancer study group. Int J Radiat Oncol Biol Phys 1987;13:665–672.

    PubMed  CAS  Google Scholar 

  24. Finney R. An evaluation of postoperative radiotherapy in hypernephroma treatment—a clinical trial. Cancer 1973;32:1332–1340.

    Article  Google Scholar 

  25. Flocks RH, Kadesky MC. Malignant neoplasms of the kidney—an analysis of 353 patients followed for five years or more. J Urol 1958;79:196–201.

    PubMed  CAS  Google Scholar 

  26. Waters CA. Preoperative irradiation of cortical renal tumors. AJR 1935;33(1):149–158.

    Google Scholar 

  27. Riches E. The place of radiotherapy in the management of parenchymal carcinoma of the kidney. J Urol 1966;93:313–320.

    Google Scholar 

  28. Finke JH, Kierstead LS, Ranieri E, Storkus WJ. Immunologic response to renal cell carcinoma. In: Bukowski RM, Novick AC, eds. Renal Cell Caracinoma: Molecular Biology, Immunology and Clinical Management. Totowa, NJ: Humana Press, 2000:39–62.

    Google Scholar 

  29. Rayman P, Wesa AK, Richmond AL, et al. Effect of renal cell carcinomas on the development of type 1 T-cell responses. Clin Cancer Res 2005;10:6360S–6366S.

    Article  Google Scholar 

  30. Gleave M, Slilali M, Fradet Y, et al. Interferon gamma-1b compared with placebo in metastatic renal cell carcinoma. N Engl J Med 1998;228:1265–1271.

    Article  Google Scholar 

  31. Figlin R, Gitlitz B, Franklin J, et al. Interleukin-2 based immunotherapy for the treatment of metastatic renal cell carcinoma: an analysis of 203 consecutively treated patients. Cancer J Sci Am Suppl 1997;1:592–597.

    Google Scholar 

  32. Tatsumi T, Kierstead LS, Ranieri E, et al. MAGE-6 encodes DR B1-1-presented epitopes recognized by CD4+ T cells derived from patients with melanoma or renal cell carcinoma. Clin Cancer Res 2003;9:947–954.

    PubMed  CAS  Google Scholar 

  33. Tatsumi T, Herrem CJ, Olson WC, et al. Disease stage variance in CD4+ and CD8+ T cell reactivity against the receptor tyrosine kinase EphA2 in patients with renal cell carcinoma. Cancer Res 2003;63:4481–4489.

    PubMed  CAS  Google Scholar 

  34. Rayman P, Uzzo RG, Kolenko V, et al. Tumor-induced dysfunction in interleukin-2 production and interleukin-2 receptor signaling: a mechanism of immune escape. Cancer J Sci Am 2000;6:581–587.

    Google Scholar 

  35. Uzzo RG, Clark PE, Rayman P, et al. Alterations in NP kappa B activation in T lymphocytes of patients with renal cell carcinoma. J Natl Cancer Inst 1999;91:718–721.

    Article  PubMed  CAS  Google Scholar 

  36. Tallberg T, Tykka H. Specific active immunotherapy in advanced renal cell carcinoma: a clinical long term follow up study. World J Urol 1986;3:234–244.

    Article  Google Scholar 

  37. Repmann R, Wagner S, Richter A. Adjuvant therapy of renal cell carcinoma with active-specific immunotherapy (ASI) using autologous tumor vaccine. Anticancer Res 1997;17:2879–2882.

    PubMed  CAS  Google Scholar 

  38. Repmann R, Goldschmidt AJ, Richter A. Adjuvant therapy of renal cell carcinoma patients with an autologous tumor cell lysate vaccine: a 5-year follow up analysis. Anticancer Res 2003;23:969–974.

    PubMed  CAS  Google Scholar 

  39. Galligioni E, Quaia M, Merlo A, et al. Adjuvant immunotherapy treatment of renal carcinoma patients with autologous tumor cells and bacillus Calmette-Guerin. Five-year results of a prospective randomized study. Cancer 1996;77:2560–2566.

    Article  PubMed  CAS  Google Scholar 

  40. Jocham D, Richter A, Hoffmann L, et al. Adjuvant autologous renal tumor cell vaccine and risk of tumor progression in patients with renal cell carcinoma after radical nephrectomy: phase III randomized controlled trial. Lancet 2004;363:594–599.

    Article  PubMed  CAS  Google Scholar 

  41. Wood CG, Escudier B, Gorelov S, et al. A multicenter randomized study of adjuvant heat-shock protein peptide-complex 96 (HSPCC-96) vaccine in patients with high-risk of recurrence after nephrectomy for renal cell carcinoma (RCC). Proc ASCO 2004;23:192.

    Google Scholar 

  42. Störkel S, Thomas W, Jacobs GH, Lippold R. Prognostic parameters in renal cell carcinoma: a new approach. Eur Urol 1989;16:416–422.

    PubMed  Google Scholar 

  43. Udono H, Srivastava PK. Comparison of tumor-specific immunogenicities of stress-induced proteins gp96, hsp90 and hsp70. J Immunol 1994;152:5395–5403.

    Google Scholar 

  44. Li Z, Srivastava PK. A critical contemplation on the role of heat shock proteins in transfer of antigenic peptides during antigen presentation. Boering Inst Mitteilungen 1994;94:37–47.

    Google Scholar 

  45. Janetzki S, Blachere NE, Daou M, et al. Generation of tumor specific cytotoxic T lymphocytes and memory T cells by immunization with tumor derived heat shock protein gp96. J Immunother 1998;21:269–276.

    Article  PubMed  CAS  Google Scholar 

  46. Amato RJ, Wood LS, Savary C, et al. Patients with renal cell carcinoma (RCC) using autologous tumor-derived heat shock protein peptide complex (HSPPC-96) with or without interleukin-2 (IL-2). Proc ASCO 2000; abstr 1782.

    Google Scholar 

  47. Amato RJ, Murray L, Wood L, et al. Active specific immunotherapy in patients with renal cell carcinoma (RCC) using autologous tumor derived heat shock protein-peptide complex 96 (HSPPC-96) vaccine. Proc ASCO 1999;abstr 1278.

    Google Scholar 

  48. Bukowski RM, Novick AC. Clinical practice guidelines: renal cell carcinoma. Cleve Clin J Med 1997;64:S1–S48.

    Google Scholar 

  49. Cockerell OC, Oliver RTD, Nethersall A. Nephrectomy combined with perioperative alpha-interferon in the treatment of advanced local and minimally metastatic renal cell cancer. Urol Int 1991;46:46–49.

    Article  PubMed  CAS  Google Scholar 

  50. Quesada JR, Rios A, Swanson D, et al. Antitumor activity of recombinant-cloned interferon alpha in metastatic renal cell carcinoma. J Clin Oncol 1985;3:1522–1528.

    PubMed  CAS  Google Scholar 

  51. Takahashi S, Tanigawa T, Imagawa M, Mimata H, Nomura Y, Ogata J. Interferon as adjunctive treatment for non-metastatic renal cell carcinoma. Br J Urol 1994;74:11–14.

    Article  PubMed  CAS  Google Scholar 

  52. Porzsolt F, on behalf of the Delta-P Study Group. Adjuvant therapy of renal cell cancer (RCC) with interferon alfa-s. Proc Am Soc Clin Oncol 1992;22:202(abstr)

    Google Scholar 

  53. Pizzocaro G, Diva L, Colavita M, et al. Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicenter randomized study. J Clin Oncol 2001;19:425–431.

    PubMed  CAS  Google Scholar 

  54. Messing EM, Manola J, Wilding G, et al. Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology/Intergroup trial. J Clin Oncol 2003;21:1214–1222.

    Article  PubMed  CAS  Google Scholar 

  55. Motzer RJ, Bacik J, Mariani T, Russo P, Mazumdar M, Reuter V. Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear cell histology. J Clin Oncol 2002;20:2376–2381.

    Article  PubMed  Google Scholar 

  56. Bukowski RM. Natural history and therapy of metastatic renal cell carcinoma: role of interleukin 2. Cancer 1997;80:1198–1220.

    Article  PubMed  CAS  Google Scholar 

  57. Yang JC, Skorry RM, Steinberg SM, et al. Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 2003;21:3127–3132.

    Article  PubMed  CAS  Google Scholar 

  58. McDermott DF, Regan MM, Clark JI, et al. Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 2005;23:133–141.

    Article  PubMed  CAS  Google Scholar 

  59. Clark J, Atkins M, Urba W, et al. Adjuvant high dose bolus interleukin-2 for patients with high risk renal cell carcinoma: a cytokine working group randomized trial. J Clin Oncol 2003;21:3133–3140.

    Article  PubMed  CAS  Google Scholar 

  60. Olencki T, Bukowski RM, Zuccaro K, et al. Adjuvant administration of subcutaneous (SC) interleukin-2 (rIL-2) in patients following resection of renal cell carcinoma: preliminary results of a pilot study. Proc Am Soc Clin Oncol 1998;17:339a (abstract).

    Google Scholar 

  61. Atzpodien J, Kirchner H, Jonas U, et al. Interleukin-2-and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a prospectively randomized trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). J Clin Oncol 2004;1;22(7):1188–1194.

    Article  PubMed  CAS  Google Scholar 

  62. Negrier S, Escudier B, Lasset C, et al. Recombinant human interleukin-2, recombinant interferon alfa-2a or both in metastatic renal cell carcinoma. N Engl J Med 1996;338:1272–1279.

    Article  Google Scholar 

  63. Migliari R, Muscas G, Solinas A, et al. Is there a role for adjuvant immunochemotherapy after radical nephrectomy in pT2−3N0M0 renal cell carcinoma. J Chemother 1995;7:240–245.

    PubMed  CAS  Google Scholar 

  64. Fossa SD, Martinelli G, Otto U, et al. Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study. Ann Oncol 1992;3:301–305.

    PubMed  CAS  Google Scholar 

  65. Motzer RJ, Rini BJ, Michaelson MD, et al. Phase II trials of SU11248 show antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma. Proc ASCO J Clin Oncol 2005;23:Abstr. 4508.

    Google Scholar 

  66. Escudier B, Szczylik T, Eisen T, et al. Randomized phase III trial of the RaF-kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). Proc ASCO J Clin Oncol 2005;23:Abstr. 4510.

    Google Scholar 

  67. Yang JC, Haworth L, Skerry M, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003;349:427–434.

    Article  PubMed  CAS  Google Scholar 

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  1. Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH

    Ronald M. Bukowski MD

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  1. Ronald M. Bukowski MD
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Editors and Affiliations

  1. Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH

    Ronald M. Bukowski MD

  2. Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH

    Andrew C. Novick MD

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© 2008 Humana Press Inc., Totowa, NJ

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Bukowski, R.M. (2008). Adjuvant Therapy of Renal Cell Carcinoma. In: Bukowski, R.M., Novick, A.C. (eds) Clinical Management of Renal Tumors. Humana Press. https://doi.org/10.1007/978-1-60327-149-3_18

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  • DOI: https://doi.org/10.1007/978-1-60327-149-3_18

  • Publisher Name: Humana Press

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