Skip to main content
Top
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

Authors: Adolfo JO Scherr, Joao Paulo SN Lima, Emma C Sasse, Carmen SP Lima, André D Sasse

Published in: BMC Cancer | Issue 1/2011

Login to get access

Abstract

Background

Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting.

Methods

Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy) versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS), disease-free survival (DFS), and severe toxicities. Risk ratios (RR), hazard ratios (HR) and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately.

Results

Ten studies (2,609 patients) were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0%) or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15%) when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy) had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group.

Conclusions

This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 2009, 59: 225-249.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 2009, 59: 225-249.CrossRefPubMed
2.
go back to reference Golimbu M, Joshi P, Sperber A, Tessler A, Al-Askari S, Morales P: Renal cell carcinoma: survival and prognostic factors. Urology. 1986, 27: 291-301.CrossRefPubMed Golimbu M, Joshi P, Sperber A, Tessler A, Al-Askari S, Morales P: Renal cell carcinoma: survival and prognostic factors. Urology. 1986, 27: 291-301.CrossRefPubMed
3.
go back to reference Minasian LM, Motzer RJ, Gluck L, Mazumdar M, Vlamis V, Krown SE: Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol. 1993, 11: 1368-1375.PubMed Minasian LM, Motzer RJ, Gluck L, Mazumdar M, Vlamis V, Krown SE: Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol. 1993, 11: 1368-1375.PubMed
4.
go back to reference Fisher RI, Rosenberg SA, Fyfe G: Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am. 2000, 6 (Suppl 1): S55-57.PubMed Fisher RI, Rosenberg SA, Fyfe G: Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am. 2000, 6 (Suppl 1): S55-57.PubMed
5.
go back to reference Pizzocaro G, Piva L, Di Fronzo G, Giongo A, Cozzoli A, Dormia E, Minervini S, Zanollo A, Fontanella U, Longo G, et al: Adjuvant medroxyprogesterone acetate to radical nephrectomy in renal cancer: 5-year results of a prospective randomized study. J Urol. 1987, 138: 1379-1381.PubMed Pizzocaro G, Piva L, Di Fronzo G, Giongo A, Cozzoli A, Dormia E, Minervini S, Zanollo A, Fontanella U, Longo G, et al: Adjuvant medroxyprogesterone acetate to radical nephrectomy in renal cancer: 5-year results of a prospective randomized study. J Urol. 1987, 138: 1379-1381.PubMed
6.
go back to reference Naito S, Kumazawa J, Omoto T, Iguchi A, Sagiyama K, Osada Y, Hiratsuka Y: Postoperative UFT adjuvant and the risk factors for recurrence in renal cell carcinoma: a long-term follow-up study. Kyushu University Urological Oncology Group. Int J Urol. 1997, 4: 8-12.CrossRefPubMed Naito S, Kumazawa J, Omoto T, Iguchi A, Sagiyama K, Osada Y, Hiratsuka Y: Postoperative UFT adjuvant and the risk factors for recurrence in renal cell carcinoma: a long-term follow-up study. Kyushu University Urological Oncology Group. Int J Urol. 1997, 4: 8-12.CrossRefPubMed
7.
go back to reference Messing EM, Manola J, Wilding G, Propert K, Fleischmann J, Crawford ED, Pontes JE, Hahn R, Trump D: Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial. J Clin Oncol. 2003, 21: 1214-1222.CrossRefPubMed Messing EM, Manola J, Wilding G, Propert K, Fleischmann J, Crawford ED, Pontes JE, Hahn R, Trump D: Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial. J Clin Oncol. 2003, 21: 1214-1222.CrossRefPubMed
8.
go back to reference Atzpodien J, Schmitt E, Gertenbach U, Fornara P, Heynemann H, Maskow A, Ecke M, Woltjen HH, Jentsch H, Wieland W, et al: Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). Br J Cancer. 2005, 92: 843-846.CrossRefPubMedPubMedCentral Atzpodien J, Schmitt E, Gertenbach U, Fornara P, Heynemann H, Maskow A, Ecke M, Woltjen HH, Jentsch H, Wieland W, et al: Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). Br J Cancer. 2005, 92: 843-846.CrossRefPubMedPubMedCentral
9.
go back to reference Parmar MK, Torri V, Stewart L: Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998, 17: 2815-2834.CrossRefPubMed Parmar MK, Torri V, Stewart L: Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998, 17: 2815-2834.CrossRefPubMed
10.
go back to reference Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR: Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007, 8: 16-CrossRefPubMedPubMedCentral Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR: Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007, 8: 16-CrossRefPubMedPubMedCentral
11.
go back to reference Sterne JAC, Egger M, Smith GD: Investigating and dealing with publication and other biases. Systematic reviews in health care: Metaanalisys in context. Edited by: Egger M, Smith GD, Altman DG. 2001, London: BMJ Publication Group, 2 Sterne JAC, Egger M, Smith GD: Investigating and dealing with publication and other biases. Systematic reviews in health care: Metaanalisys in context. Edited by: Egger M, Smith GD, Altman DG. 2001, London: BMJ Publication Group, 2
12.
14.
go back to reference Aitchison M, Bray C, Van Poppel H, Sylvester R, Graham J, Innes C, McMahon L, Vasey PA: Preliminary results from a randomized phase III trial of adjuvant interleukin-2, interferon alpha and 5-fluorouracil in patients with a high risk of relapse after nephrectomy for renal cell carcinoma (RCC). 2008 ASCO Annual Meeting; Chigaco. 2008, American Society of Clinical Oncology Aitchison M, Bray C, Van Poppel H, Sylvester R, Graham J, Innes C, McMahon L, Vasey PA: Preliminary results from a randomized phase III trial of adjuvant interleukin-2, interferon alpha and 5-fluorouracil in patients with a high risk of relapse after nephrectomy for renal cell carcinoma (RCC). 2008 ASCO Annual Meeting; Chigaco. 2008, American Society of Clinical Oncology
15.
go back to reference Clark JI, Atkins MB, Urba WJ, Creech S, Figlin RA, Dutcher JP, Flaherty L, Sosman JA, Logan TF, White R, 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.CrossRefPubMed Clark JI, Atkins MB, Urba WJ, Creech S, Figlin RA, Dutcher JP, Flaherty L, Sosman JA, Logan TF, White R, 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.CrossRefPubMed
16.
go back to reference Galligioni E, Quaia M, Merlo A, Carbone A, Spada A, Favaro D, Santarosa M, Sacco C, Talamini R: 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.CrossRefPubMed Galligioni E, Quaia M, Merlo A, Carbone A, Spada A, Favaro D, Santarosa M, Sacco C, Talamini R: 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.CrossRefPubMed
17.
go back to reference Jocham D, Richter A, Hoffmann L, Iwig K, Fahlenkamp D, Zakrzewski G, Schmitt E, Dannenberg T, Lehmacher W, von Wietersheim J, Doehn C: Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial. Lancet. 2004, 363: 594-599.CrossRefPubMed Jocham D, Richter A, Hoffmann L, Iwig K, Fahlenkamp D, Zakrzewski G, Schmitt E, Dannenberg T, Lehmacher W, von Wietersheim J, Doehn C: Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial. Lancet. 2004, 363: 594-599.CrossRefPubMed
18.
go back to reference Pizzocaro G, Piva L, Colavita M, Ferri S, Artusi R, Boracchi P, Parmiani G, Marubini E: Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study. J Clin Oncol. 2001, 19: 425-431.PubMed Pizzocaro G, Piva L, Colavita M, Ferri S, Artusi R, Boracchi P, Parmiani G, Marubini E: Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study. J Clin Oncol. 2001, 19: 425-431.PubMed
19.
go back to reference Wood C, Srivastava P, Bukowski R, Lacombe L, Gorelov AI, Gorelov S, Mulders P, Zielinski H, Hoos A, Teofilovici F, et al: An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet. 2008, 372: 145-154.CrossRefPubMed Wood C, Srivastava P, Bukowski R, Lacombe L, Gorelov AI, Gorelov S, Mulders P, Zielinski H, Hoos A, Teofilovici F, et al: An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet. 2008, 372: 145-154.CrossRefPubMed
20.
go back to reference Passalacqua R, Buzio C, Buti S, Labianca R: Adjuvant low-dose interleukin-2 (IL2) plus interferone-alpha (IFN) in operable renal cell cancer. A Phase III, randomized, multicenter, independent trial of the Italian Oncology Group for Clinical Research (GOIRC). J Clin Oncol. 2007, 25: Passalacqua R, Buzio C, Buti S, Labianca R: Adjuvant low-dose interleukin-2 (IL2) plus interferone-alpha (IFN) in operable renal cell cancer. A Phase III, randomized, multicenter, independent trial of the Italian Oncology Group for Clinical Research (GOIRC). J Clin Oncol. 2007, 25:
21.
go back to reference Margulis V, Matin SF, Tannir N, Tamboli P, Shen Y, Lozano M, Swanson DA, Jonasch E, Wood CG: Randomized trial of adjuvant thalidomide versus observation in patients with completely resected high-risk renal cell carcinoma. Urology. 2009, 73: 337-341.CrossRefPubMed Margulis V, Matin SF, Tannir N, Tamboli P, Shen Y, Lozano M, Swanson DA, Jonasch E, Wood CG: Randomized trial of adjuvant thalidomide versus observation in patients with completely resected high-risk renal cell carcinoma. Urology. 2009, 73: 337-341.CrossRefPubMed
22.
23.
go back to reference Kapoor A, Gharajeh A, Sheikh A, Pinthus J: Adjuvant and neoadjuvant small-molecule targeted therapy in high-risk renal cell carcinoma. Curr Oncol. 2009, 16 (Suppl 1): S60-66.PubMedPubMedCentral Kapoor A, Gharajeh A, Sheikh A, Pinthus J: Adjuvant and neoadjuvant small-molecule targeted therapy in high-risk renal cell carcinoma. Curr Oncol. 2009, 16 (Suppl 1): S60-66.PubMedPubMedCentral
Metadata
Title
Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis
Authors
Adolfo JO Scherr
Joao Paulo SN Lima
Emma C Sasse
Carmen SP Lima
André D Sasse
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-115

Other articles of this Issue 1/2011

BMC Cancer 1/2011 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine