Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Long-term management of bilateral, multifocal, recurrent renal carcinoma

Nature Reviews Urology volume 7, pages 267–275 (2010)Cite this article

Subjects

Abstract

Patients with bilateral multifocal renal cell carcinoma are at increased risk of developing locally recurrent or de novo tumors after nephron-sparing procedures. When dealing with recurrent renal masses the options are limited to observation, total nephrectomy, ablation, or repeat surgical intervention. The main reason for recurrence after nephron-sparing surgery is likely to be the presence of multifocal disease, which is identified in 4.3–25.0% of radical nephrectomy specimen. Bilateral renal involvement is seen in almost 90% of cases of multifocal renal carcinoma, and conversely the majority of patients with bilateral disease will have multifocal tumors. Many patients who are treated for multifocal disease, therefore, require subsequent surgical interventions. The outcome data for repeat renal interventions demonstrate reasonable functional and oncologic outcomes despite higher rates of perioperative complications. Our own results support the use of reoperative renal surgery rather than total nephrectomy and renal replacement therapy.

Key Points

  • Patients with bilateral multifocal renal cell carcinoma are likely to have locally recurrent disease and require repeat surgical interventions

  • Renal surgery for bilateral multifocal recurrent renal masses is technically demanding and associated with high rates of perioperative complications

  • Repeat renal intervention results in reasonable functional and oncologic outcomes

  • Renal replacement therapy is associated with high levels of morbidity and mortality

  • Faced with limited options for treating this patient population, we argue that repeat nephron-sparing intervention is a better alternative than nephrectomy and renal replacement therapy

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: CT showing a left kidney that was previously treated with radiofrequency ablation.
Figure 2: Algorithm for management of patients presenting with bilateral renal masses.

Similar content being viewed by others

References

  1. Jemal, A. et al. Cancer statistics, 2009. CA Cancer J. Clin. 59, 225–249 (2009).

    Google Scholar 

  2. Chow, W. H., Devesa, S. S., Warren, J. L. & Fraumeni, J. F. Jr. Rising incidence of renal cell cancer in the United States. JAMA 281, 1628–1631 (1999).

    CAS  PubMed  Google Scholar 

  3. Hollingsworth, J. M., Miller, D. C., Daignault, S. & Hollenbeck, B. K. Rising incidence of small renal masses: a need to reassess treatment effect. J. Natl Cancer Inst. 98, 1331–1334 (2006).

    Google Scholar 

  4. Janzen, N. K., Kim, H. L., Figlin, R. A. & Belldegrun, A. S. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol. Clin. North Am. 30, 843–852 (2003).

    Article  Google Scholar 

  5. Lam, J. S., Leppert, J. T., Figlin, R. A. & Belldegrun, A. S. Surveillance following radical or partial nephrectomy for renal cell carcinoma. Curr. Urol. Rep. 6, 7–18 (2005).

    Article  Google Scholar 

  6. Levy, D. A., Slaton, J. W., Swanson, D. A. & Dinney, C. P. Stage specific guidelines for surveillance after radical nephrectomy for local renal cell carcinoma. J. Urol. 159, 1163–1167 (1998).

    Article  CAS  Google Scholar 

  7. Stephenson, A. J. et al. Guidelines for the surveillance of localized renal cell carcinoma based on the patterns of relapse after nephrectomy. J. Urol. 172, 58–62 (2004).

    Article  Google Scholar 

  8. Steinbach, F. et al. Treatment of renal cell carcinoma in von Hippel-Lindau disease: a multicenter study. J. Urol. 153, 1812–1816 (1995).

    Article  CAS  Google Scholar 

  9. Blute, M. L. et al. The effect of bilaterality, pathological features and surgical outcome in nonhereditary renal cell carcinoma. J. Urol. 169, 1276–1281 (2003).

    Article  Google Scholar 

  10. Boorjian, S. A., Crispen, P. L., Lohse, C. M., Leibovich, B. C. & Blute, M. L. The impact of temporal presentation on clinical and pathological outcomes for patients with sporadic bilateral renal masses. Eur. Urol. 54, 855–863 (2008).

    Article  Google Scholar 

  11. Klatte, T. et al. Clinicopathological features and prognosis of synchronous bilateral renal cell carcinoma: an international multicentre experience. BJU Int. 100, 21–25 (2007).

    Article  Google Scholar 

  12. Krambeck, A. et al. Long-term outcome of multiple ipsilateral renal tumours found at the time of planned nephron-sparing surgery. BJU Int. 101, 1375–1379 (2008).

    Article  Google Scholar 

  13. Gnarra, J. R. et al. Molecular genetic studies of sporadic and familial renal cell carcinoma. Urol. Clin. North Am. 20, 207–216 (1993).

    CAS  PubMed  Google Scholar 

  14. Linehan, W. M. et al. Genetic basis of cancer of the kidney: disease-specific approaches to therapy. Clin. Cancer Res. 10, 6282S–6289S (2004).

    Article  CAS  Google Scholar 

  15. Linehan, W. M. Genetic basis of bilateral renal cancer: implications for evaluation and management. J. Clin. Oncol. 27, 3731–3733 (2009).

    Article  Google Scholar 

  16. Blute, M. L., Amling, C. L., Bryant, S. C. & Zincke, H. Management and extended outcome of patients with synchronous bilateral solid renal neoplasms in the absence of von Hippel-Lindau disease. Mayo Clin. Proc. 75, 1020–1026 (2000).

    Article  CAS  Google Scholar 

  17. Crispen, P. L., Lohse, C. M. & Blute, M. L. Multifocal renal cell carcinoma: clinicopathologic features and outcomes for tumors </=4 cm. Adv. Urol. 2008, 518091 (2008).

    Article  Google Scholar 

  18. Dimarco, D. S., Lohse, C. M., Zincke, H., Cheville, J. C. & Blute, M. L. Long-term survival of patients with unilateral sporadic multifocal renal cell carcinoma according to histologic subtype compared with patients with solitary tumors after radical nephrectomy. Urology 64, 462–467 (2004).

    Article  Google Scholar 

  19. Lang, H. et al. Prognostic value of multifocality on progression and survival in localized renal cell carcinoma. Eur. Urol. 45, 749–753 (2004).

    Article  Google Scholar 

  20. Lowrance, W. T. et al. Developments in the surgical management of sporadic synchronous bilateral renal tumours. BJU Int. doi:10.1111/j.1464-410X.2009.08844.x.

  21. Patel, M. I. et al. Long-term follow-up of bilateral sporadic renal tumors. Urology 61, 921–925 (2003).

    Article  Google Scholar 

  22. Richstone, L. et al. Multifocal renal cortical tumors: frequency, associated clinicopathological features and impact on survival. J. Urol. 171, 615–620 (2004).

    Article  Google Scholar 

  23. Grimaldi, G., Reuter, V. & Russo, P. Bilateral non-familial renal cell carcinoma. Ann. Surg. Oncol. 5, 548–552 (1998).

    Article  CAS  Google Scholar 

  24. Siemer, S. et al. Bilateral kidney tumor. Therapy management and histopathological results with long-term follow-up of 66 patients [German]. Urologe A 40, 114–120 (2001).

    Article  CAS  Google Scholar 

  25. Zincke, H. & Swanson, S. K. Bilateral renal cell carcinoma: influence of synchronous and asynchronous occurrence on patient survival. J. Urol. 128, 913–915 (1982).

    Article  CAS  Google Scholar 

  26. Wunderlich, H. et al. Multifocality in renal cell carcinoma: a bilateral event? Urol. Int. 63, 160–163 (1999).

    Article  CAS  Google Scholar 

  27. Klatte, T. et al. Metachronous bilateral renal cell carcinoma: risk assessment, prognosis and relevance of the primary-free interval. J. Urol. 177, 2081–2086 (2007).

    Article  Google Scholar 

  28. Baltaci, S. et al. Influence of tumor stage, size, grade, vascular involvement, histological cell type and histological pattern on multifocality of renal cell carcinoma. J. Urol. 164, 36–39 (2000).

    Article  CAS  Google Scholar 

  29. Cheng, W. S., Farrow, G. M. & Zincke, H. The incidence of multicentricity in renal cell carcinoma. J. Urol. 146, 1221–1223 (1991).

    Article  CAS  Google Scholar 

  30. Gohji, K. et al. Multifocal renal cell carcinoma in Japanese patients with tumors with maximal diameters of 50 mm or less. J. Urol. 159, 1144–1147 (1998).

    Article  CAS  Google Scholar 

  31. Junker, K. et al. Clonal origin of multifocal renal cell carcinoma as determined by microsatellite analysis. J. Urol. 168, 2632–2636 (2002).

    Article  Google Scholar 

  32. Karayiannis, A., Varkarakis, I., Chort, M., Alivizatos, G. & Fragiskos, S. Multifocality of renal cell tumors is a factor to consider before performing a partial nephrectomy. Anticancer Res. 22, 3103–3107 (2002).

    PubMed  Google Scholar 

  33. Kletscher, B. A., Qian, J., Bostwick, D. G., Andrews, P. E. & Zincke, H. Prospective analysis of multifocality in renal cell carcinoma: influence of histological pattern, grade, number, size, volume and deoxyribonucleic acid ploidy. J. Urol. 153, 904–906 (1995).

    Article  CAS  Google Scholar 

  34. Mukamel, E., Konichezky, M., Engelstein, D. & Servadio, C. Incidental small renal tumors accompanying clinically overt renal cell carcinoma. J. Urol. 140, 22–24 (1988).

    Article  CAS  Google Scholar 

  35. Nissenkorn, I. & Bernheim, J. Multicentricity in renal cell carcinoma. J. Urol. 153, 620–622 (1995).

    Article  CAS  Google Scholar 

  36. Oya, M., Nakamura, K., Baba, S., Hata, J. & Tazaki, H. Intrarenal satellites of renal cell carcinoma: histopathologic manifestation and clinical implication. Urology 46, 161–164 (1995).

    Article  CAS  Google Scholar 

  37. Saiki, S. et al. Multicentricity and concomitant tumors in renal cell carcinoma: analysis by serial section of resected kidneys [Japanese]. Hinyokika Kiyo 41, 725–729 (1995).

    CAS  PubMed  Google Scholar 

  38. Schlichter, A., Schubert, R., Werner, W., Zermann, D. H. & Schubert, J. How accurate is diagnostic imaging in determination of size and multifocality of renal cell carcinoma as a prerequisite for nephron-sparing surgery? Urol. Int. 64, 192–197 (2000).

    Article  CAS  Google Scholar 

  39. Whang, M. et al. The incidence of multifocal renal cell carcinoma in patients who are candidates for partial nephrectomy. J. Urol. 154, 968–970 (1995).

    Article  CAS  Google Scholar 

  40. Ljungberg, B., Alamdari, F. I., Rasmuson, T. & Roos, G. Follow-up guidelines for nonmetastatic renal cell carcinoma based on the occurrence of metastases after radical nephrectomy. BJU Int. 84, 405–411 (1999).

    Article  CAS  Google Scholar 

  41. Walther, M. M., Lubensky, I. A., Venzon, D., Zbar, B. & Linehan, W. M. Prevalence of microscopic lesions in grossly normal renal parenchyma from patients with von Hippel-Lindau disease, sporadic renal cell carcinoma and no renal disease: clinical implications. J. Urol. 154, 2010–2014 (1995).

    Article  CAS  Google Scholar 

  42. Ornstein, D. K. et al. Prevalence of microscopic tumors in normal appearing renal parenchyma of patients with hereditary papillary renal cancer. J. Urol. 163, 431–433 (2000).

    Article  CAS  Google Scholar 

  43. Pavlovich, C. P. et al. Renal tumors in the Birt-Hogg-Dube syndrome. Am. J. Surg. Pathol. 26, 1542–1552 (2002).

    Article  Google Scholar 

  44. Fetner, C. D., Barilla, D. E., Scott, T., Ballard, J. & Peters, P. Bilateral renal cell carcinoma in von Hippel–Lindau syndrome: treatment with staged bilateral nephrectomy and hemodialysis. J. Urol. 117, 534–536 (1977).

    Article  CAS  Google Scholar 

  45. Pearson, J. C., Weiss, J. & Tanagho, E. A. A plea for conservation of kidney in renal adenocarcinoma associated with von Hippel–Lindau disease. J. Urol. 124, 910–912 (1980).

    Article  CAS  Google Scholar 

  46. Berg, S. et al. The surgical management of hereditary multifocal renal carcinoma. J. Urol. 126, 313–315 (1981).

    Article  CAS  Google Scholar 

  47. Frydenberg, M., Malek, R. S. & Zincke, H. Conservative renal surgery for renal cell carcinoma in von Hippel–Lindau's disease. J. Urol. 149, 461–464 (1993).

    Article  CAS  Google Scholar 

  48. Loughlin, K. R. & Gittes, R. F. Urological management of patients with von Hippel–Lindau's disease. J. Urol. 136, 789–791 (1986).

    Article  CAS  Google Scholar 

  49. Lund, G. O., Fallon, B., Curtis, M. A. & Williams, R. D. Conservative surgical therapy of localized renal cell carcinoma in von Hippel–Lindau disease. Cancer 74, 2541–2545 (1994).

    Article  CAS  Google Scholar 

  50. Malek, R. S., Omess, P. J., Benson, R. C. Jr & Zincke, H. Renal cell carcinoma in von Hippel–Lindau syndrome. Am. J. Med. 82, 236–238 (1987).

    Article  CAS  Google Scholar 

  51. Walther, M. M. et al. Parenchymal sparing surgery in patients with hereditary renal cell carcinoma. J. Urol. 153, 913–916 (1995).

    Article  CAS  Google Scholar 

  52. Foley, D. P. et al. Long-term outcomes of kidney transplantation in recipients 60 years of age and older at the University of Florida. Clin. Transpl. 101–109 (2005).

  53. Hernandez, D. et al. Predicting delayed graft function and mortality in kidney transplantation. Transplant. Rev. (Orlando) 22, 21–26 (2008).

    Article  Google Scholar 

  54. Schold, J., Srinivas, T. R., Sehgal, A. R. & Meier-Kriesche, H. U. Half of kidney transplant candidates who are older than 60 years now placed on the waiting list will die before receiving a deceased-donor transplant. Clin. J. Am. Soc. Nephrol. 4, 1239–1245 (2009).

    Article  Google Scholar 

  55. Kasiske, B. L. et al. The evaluation of renal transplantation candidates: clinical practice guidelines. Am. J. Transplant. 1 (Suppl. 2), 3–95 (2001).

    PubMed  Google Scholar 

  56. United States Renal Data System. 2007 Annual Data Report, Bethesda, MD. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), US Department of Health and Human Services (DHHS) (2007).

  57. Lin, S. J. et al. The association between length of post-kidney transplant hospitalization and long-term graft and recipient survival. Clin. Transplant. 20, 245–252 (2006).

    Article  Google Scholar 

  58. Rocco, M. V., Frankenfield, D. L., Hopson, S. D. & McClellan, W. M. Relationship between clinical performance measures and outcomes among patients receiving long-term hemodialysis. Ann. Intern. Med. 145, 512–519 (2006).

    Article  Google Scholar 

  59. Foley, R. N., Parfrey, P. S. & Sarnak, M. J. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am. J. Kidney Dis. 32, S112–S119 (1998).

    Article  CAS  Google Scholar 

  60. Neil, N. et al. The financial implications for Medicare of greater use of peritoneal dialysis. Clin. Ther. 31, 880–888 (2009).

    Article  Google Scholar 

  61. Go, A. S., Chertow, G. M., Fan, D., McCulloch, C. E. & Hsu, C. Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Engl. J. Med. 351, 1296–1305 (2004).

    Article  CAS  Google Scholar 

  62. Huang, W. C. et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol. 7, 735–740 (2006).

    Article  Google Scholar 

  63. Huang, W. C., Elkin, E. B., Levey, A. S., Jang, T. L. & Russo, P. Partial nephrectomy versus radical nephrectomy in patients with small renal tumors—is there a difference in mortality and cardiovascular outcomes? J. Urol. 181, 55–61 (2009).

    Article  Google Scholar 

  64. Thompson, R. H. et al. Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared with partial nephrectomy. J. Urol. 179, 468–471 (2008).

    Article  Google Scholar 

  65. Sarnak, M. J. et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 108, 2154–2169 (2003).

    Article  Google Scholar 

  66. Weiner, D. E. et al. Cardiovascular outcomes and all-cause mortality: exploring the interaction between CKD and cardiovascular disease. Am. J. Kidney Dis. 48, 392–401 (2006).

    Article  Google Scholar 

  67. Koenig, P. et al. Kidney cancer and the risk for chronic kidney disease: matched-paired comparison with living donors [abstract]. J. Urol. 179, 171 (2009).

    Google Scholar 

  68. Hwang, J. J. et al. Radio frequency ablation of small renal tumors: intermediate results. J. Urol. 171, 1814–1818 (2004).

    Article  CAS  Google Scholar 

  69. Walther, M. C. et al. A phase 2 study of radio frequency interstitial tissue ablation of localized renal tumors. J. Urol. 163, 1424–1427 (2000).

    Article  CAS  Google Scholar 

  70. Kowalczyk, K. J. et al. Partial nephrectomy after previous radio frequency ablation: The National Cancer Institute Experience. J. Urol. 182, 2158–2163 (2009).

    Article  Google Scholar 

  71. Bratslavsky, G. et al. Salvage partial nephrectomy for hereditary renal cancer: feasibility and outcomes. J. Urol. 179, 67–70 (2008).

    Article  Google Scholar 

  72. Johnson, A. et al. Feasibility and outcomes of repeat partial nephrectomy. J. Urol. 180, 89–93 (2008).

    Article  Google Scholar 

  73. Herring, J. C. et al. Parenchymal sparing surgery in patients with hereditary renal cell carcinoma: 10-year experience. J. Urol. 165, 777–781 (2001).

    Article  CAS  Google Scholar 

  74. Ghavamian, R. et al. Renal cell carcinoma in the solitary kidney: an analysis of complications and outcome after nephron sparing surgery. J. Urol. 168, 454–459 (2002).

    Article  Google Scholar 

  75. Saranchuk, J. W., Touijer, A. K., Hakimian, P., Snyder, M. E. & Russo, P. Partial nephrectomy for patients with a solitary kidney: the Memorial Sloan–Kettering experience. BJU Int. 94, 1323–1328 (2004).

    Article  Google Scholar 

  76. Thompson, R. H., Leibovich, B. C., Lohse, C. M., Zincke, H. & Blute, M. L. Complications of contemporary open nephron sparing surgery: a single institution experience. J. Urol. 174, 855–868 (2005).

    Article  Google Scholar 

  77. Magera, J. S. Jr et al. Analysis of repeat nephron sparing surgery as a treatment option in patients with a solid mass in a renal remnant. J. Urol. 179, 853–856 (2008).

    Article  Google Scholar 

  78. Stephenson, A. J., Hakimi, A. A., Snyder, M. E. & Russo, P. Complications of radical and partial nephrectomy in a large contemporary cohort. J. Urol. 171, 130–134 (2004).

    Article  Google Scholar 

  79. Nguyen, C. T. et al. Surgical salvage of renal cell carcinoma recurrence after thermal ablative therapy. J. Urol. 180, 104–109 (2008).

    Article  Google Scholar 

  80. Liu, N. W. et al. Repeat partial nephrectomy on the solitary kidney: surgical, functional, and oncologic outcomes. J. Urol. (in press).

  81. Walther, M. M. et al. Renal cancer in families with hereditary renal cancer: prospective analysis of a tumor size threshold for renal parenchymal sparing surgery. J. Urol. 161, 1475–1479 (1999).

    Article  CAS  Google Scholar 

  82. Duffey, B. G. et al. The relationship between renal tumor size and metastases in patients with von Hippel–Lindau disease. J. Urol. 172, 63–65 (2004).

    Article  Google Scholar 

  83. Choyke, P. L. et al. Intraoperative ultrasound during renal parenchymal sparing surgery for hereditary renal cancers: a 10-year experience. J. Urol. 165, 397–400 (2001).

    Article  CAS  Google Scholar 

  84. Walther, M. M. et al. Evaluation of color Doppler intraoperative ultrasound in parenchymal sparing renal surgery. J. Urol. 152, 1984–1987 (1994).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

Author information

Authors and Affiliations

  1. Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, 20892-1414, MD, USA

    Gennady Bratslavsky & W. Marston Linehan

Authors
  1. Gennady Bratslavsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Marston Linehan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gennady Bratslavsky.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bratslavsky, G., Linehan, W. Long-term management of bilateral, multifocal, recurrent renal carcinoma. Nat Rev Urol 7, 267–275 (2010). https://doi.org/10.1038/nrurol.2010.44

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2010.44

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer