The adjuvant treatment of kidney cancer: a multidisciplinary outlook

ABSTRACT Approximately 70% of cases of kidney cancer are localized or locally advanced at diagnosis. Among patients who undergo surgery for these cancers, 30–35% will eventually develop

potentially fatal metachronous distant metastases. Effective adjuvant treatments are urgently needed to reduce the risk of recurrence of kidney cancer and of dying of metastatic disease. To

date, almost all of the tested adjuvant agents have failed to demonstrate any benefit. Only two trials of an autologous renal tumour cell vaccine and of the vascular endothelial growth

factor receptor (VEGFR) tyrosine kinase inhibitor sunitinib have shown positive results, but these have been criticized for methodological reasons and conflicting data, respectively. The

results of two additional trials of targeted agents as adjuvant therapies have not yet been published. Novel immune checkpoint inhibitors are promising approaches to adjuvant therapy in

kidney cancer, and a number of trials are now underway. An important component of the management of patients with kidney cancer, particularly those who undergo radical resection for

localized renal cell carcinoma, is the preservation of kidney function to reduce morbidity and mortality. The optimal management of these patients therefore requires a multidisciplinary

approach involving nephrologists, oncologists, urologists and pathologists. KEY POINTS * Effective adjuvant treatments for kidney cancer are needed to reduce the risk of recurrence and of

dying of metastatic disease. * To date, almost all of the tested adjuvant agents have failed to demonstrate any benefit in clinical trials; the two positive trials were criticized for

methodological reasons and conflicting results. * Only one drug — sunitinib — has been approved for the adjuvant treatment of kidney cancer in the USA; however, this drug has not been

approved as an adjuvant therapy in Europe. * Positive results with immune checkpoint inhibitors in metastatic renal cell carcinoma (RCC) suggest that these agents might also be effective

adjuvant therapies; trials of these agents are underway. * Preservation of kidney function in patients with RCC is important to reduce morbidity; therefore, multidisciplinary management

should be mandatory for almost all patients with radically resected kidney cancer. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

institution ACCESS OPTIONS Access through your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $29.99 / 30 days

cancel any time Learn more Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink *

Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional

subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ADJUVANT THERAPY OPTIONS IN RENAL CELL CARCINOMA — TARGETING THE METASTATIC CASCADE Article 11

November 2022 COMPLEMENTARY ROLES OF SURGERY AND SYSTEMIC TREATMENT IN CLEAR CELL RENAL CELL CARCINOMA Article 11 May 2022 UNDERSTANDING AND INTEGRATING CYTOREDUCTIVE NEPHRECTOMY WITH

IMMUNE CHECKPOINT INHIBITORS IN THE MANAGEMENT OF METASTATIC RCC Article 03 July 2023 REFERENCES * Ferlay, J. et al. Cancer incidence and mortality worldwide: sources, methods and major

patterns in GLOBOCAN 2012. _Int. J. Cancer_ 136, E359–E386 (2015). Article  CAS  PubMed  Google Scholar  * American Cancer Society. Key statistics about kidney cancer. _cancer.org_

https://www.cancer.org/cancer/kidney-cancer/about/key-statistics.html (updated 4 Jan 2018). * 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  PubMed  Google Scholar  * Gupta, K., Miller, J. D., Li, J. Z., Russel, M. W. & Charbonneau,

C. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. _Cancer Treat. Rev._ 34, 193–205 (2008). Article  PubMed  Google Scholar  * American

Cancer Society. Survival rates for kidney cancer. _cancer.org_ https://www.cancer.org/cancer/kidney-cancer/detection-diagnosis-staging/survival-rates.html (updated 31 Jan 2019). * Massari,

F. et al. Adjuvant therapy in renal cell carcinoma. _Cancer Treat. Rev._ 60, 152–157 (2017). Article  CAS  PubMed  Google Scholar  * Porta, C., Chiellino, S., Ferrari, A., Mariucci, S. &

Liguigli, W. Pharmacotherapy for treating metastatic clear cell renal cell carcinoma. _Expert Opin. Pharmacother._ 18, 205–216 (2017). Article  CAS  PubMed  Google Scholar  * Zisman, A. et

al. Improved prognostication of renal cell carcinoma using an integrated staging system. _J. Clin. Oncol._ 19, 1649–1657 (2001). Article  CAS  PubMed  Google Scholar  * Leibovich, B. C. et

al. Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma: a stratification tool for prospective clinical trials. _Cancer_ 97, 1663–1671

(2003). Article  PubMed  Google Scholar  * Tan, M. H. et al. Comparison of the UCLA Integrated Staging System and the Leibovich score in survival prediction for patients with nonmetastatic

clear cell renal cell carcinoma. _Urology_ 75, 1365–1370 (2010). Article  PubMed  Google Scholar  * Frank, I. et al. An outcome prediction model for patients with clear cell renal cell

carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. _J. Urol._ 168, 2395–2400 (2002). Article  PubMed  Google Scholar  * Karakiewicz,

P. I. et al. Multi-institutional validation of a new renal cancer-specific survival nomogram. _J. Clin. Oncol._ 25, 1316–1322 (2007). Article  PubMed  Google Scholar  * Kattan, M. W.,

Reuter, V., Motzer, R. J., Katz, J. & Russo, P. A postoperative prognostic nomogram for renal cell carcinoma. _J Urol._ 166, 63–67 (2001). Article  CAS  PubMed  Google Scholar  * Pal, S.

K. & Haas, N. B. Adjuvant therapy for renal cell carcinoma: past, present, and future. _Oncologist_ 19, 851–859 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Brooks,

S. A. et al. ClearCode34: a prognostic risk predictor for localized clear cell renal cell carcinoma. _Eur. Urol._ 66, 77–84 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  *

Brannon, A. R. et al. Molecular stratification of clear cell renal cell carcinoma by consensus clustering reveals distinct subtypes and survival patterns. _Genes Cancer_ 1, 152–163 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar  * Rini, B. et al. A 16-gene assay to predict recurrence after surgery in localised renal cell carcinoma: development and validation

studies. _Lancet Oncol._ 16, 676–685 (2015). Article  CAS  PubMed  Google Scholar  * Kapur, P. et al. Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell

carcinoma: a retrospective analysis with independent validation. _Lancet Oncol._ 14, 159–167 (2013). Article  CAS  PubMed  PubMed Central  Google Scholar  * Kjaer, M. et al. A randomized

trial of postoperative radiotherapy versus observation in stage II and III renal adenocarcinoma. A study by the Copenhagen Renal Cancer Study Group. _Scand. J. Urol. Nephrol._ 21, 285–289

(1987). Article  CAS  PubMed  Google Scholar  * Pizzocaro, G. et al. Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized

study. _J. Clin. Oncol._ 19, 425–431 (2001). Article  CAS  PubMed  Google Scholar  * Messing, E. M. et al. 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._ 21, 1214–1222 (2003). Article  CAS  PubMed  Google Scholar  * Clark, J. I. 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._ 21, 3133–3140 (2003). Article  CAS  PubMed  Google Scholar

  * Atzpodien, J. 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_ 92, 843–846 (2005). Article  CAS  PubMed  PubMed Central  Google Scholar  *

Passalacqua, R. et al. Adjuvant low-dose Interleukin-2 (IL-2) plus Interferon-α (IFN-α) in operable renal cell carcinoma (RCC): a phase III, randomized, multicentre trial of the Italian

Oncology Group for Clinical Research (GOIRC). _J. Immunother._ 37, 440–447 (2014). Article  CAS  PubMed  Google Scholar  * Aitchison, M. et al. Adjuvant 5-flurouracil, alpha-interferon and

interleukin-2 versus observation in patients at high risk of recurrence after nephrectomy for renal cell carcinoma: results of a phase III randomised European Organisation for Research and

Treatment of Cancer (Genito-Urinary Cancers Group)/National Cancer Research Institute trial. _Eur. J. Cancer_ 50, 70–77 (2014). Article  CAS  PubMed  Google Scholar  * Adler, A. et al.

Active specific immunotherapy of renal cell carcinoma patients: a prospective randomized study of hormono-immuno-versus hormonotherapy. Preliminary report of immunological and clinical

aspects. _J. Biol. Response Mod._ 6, 610–624 (1987). CAS  PubMed  Google Scholar  * Galligioni, E. et al. Adjuvant immunotherapy treatment of renal carcinoma patients with autologous tumor

cells and bacillus Calmette-Guèrin: five-year results of a prospective randomized study. _Cancer_ 77, 2560–2566 (1996). Article  CAS  PubMed  Google Scholar  * Jocham, D. et al. 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_ 363,

594–599 (2004). THIS TRIAL IS THE ONLY FORMALLY POSITIVE STUDY OF ADJUVANT THERAPY IN RCC; HOWEVER, IT HAS BEEN HEAVILY CRITICIZED. Article  CAS  PubMed  Google Scholar  * Wood, C. 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_ 372, 145–154 (2008). Article  CAS  PubMed  Google Scholar  * Pizzocaro, G. et al. Adjuvant medroxyprogesterone acetate to radical nephrectomy

in renal cancer: 5-year results of a prospective randomized study. _J. Urol._ 138, 1379–1381 (1987). Article  CAS  PubMed  Google Scholar  * Naito, S. et al. 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._ 4, 8–12 (1997). Article  CAS  PubMed 

Google Scholar  * Margulis, V. et al. Randomized trial of adjuvant thalidomide versus observation in patients with completely resected high-risk renal cell carcinoma. _Urology_ 73, 337–341

(2009). Article  PubMed  Google Scholar  * Chamie, K. et al. Adjuvant weekly girentuximab following nephrectomy for high-risk renal cell carcinoma: the ARISER randomized clinical trial.

_JAMA Oncol._ 3, 913–920 (2017). Article  PubMed  Google Scholar  * Supuran, C. T. Carbonic anhydrase inhibition and the management of hypoxic tumors. _Metabolites_ 7, 48 (2017). Article 

PubMed  PubMed Central  Google Scholar  * Kramar, A. et al. Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project.

_Ann. Oncol._ 26, 2392–2398 (2015). Article  CAS  PubMed  Google Scholar  * Massari, F. et al. Adjuvant treatment for resected renal cell carcinoma: are all strategies equally negative?

Potential implications for trial design with targeted agents. _Clin. Genitourin. Cancer_ 11, 471–476 (2013). Article  PubMed  Google Scholar  * Gnarra, J. R. et al. Mutations of the VHL

tumour suppressor gene in renal carcinoma. _Nat. Genet._ 7, 85–90 (1994). Article  CAS  PubMed  Google Scholar  * Shuin, T. et al. Frequent somatic mutations and loss of heterozygosity of

the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas. _Cancer Res._ 54, 2852–2855 (1994). CAS  PubMed  Google Scholar  * Herman, J. G. et al. Silencing of the

VHL tumor-suppressor gene by DNA methylation in renal carcinoma. _Proc. Natl Acad. Sci. USA_ 91, 9700–9704 (1994). Article  CAS  PubMed  PubMed Central  Google Scholar  * Gruber, M. &

Simon, M. C. Hypoxia-inducible factors, hypoxia, and tumor angiogenesis. _Curr. Opin. Hematol._ 13, 169–174 (2006). Article  CAS  PubMed  Google Scholar  * Shen, C. & Kaelin, W. G. The

VHL/HIF axis in clear cell renal carcinoma. _Semin. Cancer Biol._ 23, 18–25 (2013). Article  CAS  PubMed  Google Scholar  * Haas, N. B. et al. Adjuvant sunitinib or sorafenib for high-risk,

non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. _Lancet_ 387, 2008–2016 (2016). THIS TRIAL OF A TARGETED AGENT AS

ADJUVANT THERAPY REPORTS NEGATIVE RESULTS. Article  CAS  PubMed  PubMed Central  Google Scholar  * Ravaud, A. et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy.

_N. Engl. J. Med._ 375, 2246–2254 (2016). THIS ADJUVANT STUDY OF SUNITINIB IN RCC IS POSITIVE IN TERMS OF DFS (ITS PRIMARY END POINT) BUT NOT IN TERMS OF OS. Article  CAS  PubMed  Google

Scholar  * Motzer, R. J. et al. Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma. _J.

Clin. Oncol._ 35, 3916–3923 (2017). THIS TRIAL OF A TARGETED AGENT AS ADJUVANT THERAPY ALSO REPORTS NEGATIVE RESULTS. Article  CAS  PubMed  PubMed Central  Google Scholar  * Gross-Goupil, M.

et al. Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III randomized ATLAS trial. _Ann. Oncol._ 29, 2371–2378 (2018). Article  CAS  PubMed

  PubMed Central  Google Scholar  * US National Library of Medicine. _ClinicalTrials.gov_ https://www.clinicaltrials.gov/ct2/show/NCT00492258 (2013). THIS IS THE LATEST NEGATIVE TRIAL

INVESTIGATING A VEGFR TKI. * U.S. Food and Drug Administration. FDA approves sunitinib malate for adjuvant treatment of renal cell carcinoma. _FDA.gov_

https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm585686.htm (updated 16 Aug 2018). * Haas, N. B. et al. Adjuvant treatment for high-risk clear cell renal cancer: updated results

of a high-risk subset of the ASSURE randomized trial. _JAMA Oncol._ 3, 1249–1252 (2017). Article  PubMed  PubMed Central  Google Scholar  * Sternberg, C. et al. Pazopanib exposure

relationship with clinical efficacy and safety in the adjuvant treatment of advanced renal cell carcinoma. _Clin. Cancer Res._ 24, 3005–3013 (2018). Article  CAS  PubMed  PubMed Central 

Google Scholar  * Bex, A. et al. Updated European Association of Urology guidelines regarding adjuvant therapy for renal cell carcinoma. _Eur. Urol._ 71, 719–722 (2017). Article  PubMed 

Google Scholar  * European Medicines Agency. Withdrawal assessment report: Sutent. _ema.europa.eu_

https://www.ema.europa.eu/documents/withdrawal-report/withdrawal-assessment-report-sutent_en.pdf (2018). * US National Library of Medicine. _ClinicalTrials.gov_

https://www.clinicaltrials.gov/ct2/show/NCT01120249 (2018). * Vasudev, N. S. & Reynolds, A. R. Anti-angiogenic therapy for cancer: current progress, unresolved questions and future

directions. _Angiogenesis_ 17, 471–494 (2014). Article  CAS  PubMed  PubMed Central  Google Scholar  * Kim, B. J. et al. The role of targeted agents in the adjuvant treatment of colon

cancer: a meta-analysis of randomized phase III studies and review. _Oncotarget_ 8, 31112–31118 (2017). Article  PubMed  PubMed Central  Google Scholar  * Motzer, R. J. et al. Nivolumab

versus everolimus in advanced renal-cell carcinoma. _N. Engl. J. Med._ 373, 1803–1813 (2015). Article  CAS  PubMed  PubMed Central  Google Scholar  * Motzer, R. J. et al. Nivolumab plus

ipilimumab versus sunitinib in advanced renal-cell carcinoma. _N. Engl. J. Med._ 378, 1277–1290 (2018). THIS TRIAL ESTABLISHES A NEW STANDARD OF CARE FOR THE FIRST-LINE TREATMENT OF

METASTATIC RCC. Article  CAS  PubMed  PubMed Central  Google Scholar  * Motzer, R. J. et al. IMmotion151: a randomized phase III study of atezolizumab plus bevacizumab versus sunitinib in

untreated metastatic Renal Cell Carcinoma (mRCC) [abstract]. _J. Clin. Oncol._ 36 (Suppl. 6), 578 (2018). Article  Google Scholar  * Motzer, R. J. et al. JAVELIN Renal 101: a randomized,

phase 3 study of avelumab+axitinib versus sunitinib as first-line treatment of advanced renal cell carcinoma (aRCC) [abstract]. _Ann. Oncol._ 29 (Suppl. 8), LBAA6_PR (2018). Google Scholar 

* US National Library of Medicine. _ClinicalTrials.gov_ https://www.clinicaltrials.gov/ct2/show/NCT03055013 (2019). * US National Library of Medicine. _ClinicalTrials.gov_

https://www.clinicaltrials.gov/ct2/show/NCT03024996 (2019). * US National Library of Medicine. _ClinicalTrials.gov_ https://www.clinicaltrials.gov/ct2/show/NCT03142334 (2019). * US National

Library of Medicine. _ClinicalTrials.gov_ https://www.clinicaltrials.gov/ct2/show/NCT03288532 (2018). * US National Library of Medicine. _ClinicalTrials.gov_

https://www.clinicaltrials.gov/ct2/show/NCT03138512 (2019). * Liu, J. et al. Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease. _Cancer

Discov._ 6, 1382–1399 (2016). Article  CAS  PubMed  Google Scholar  * Hung, P. H. et al. Increased risk of end-stage renal disease in patients with renal cell carcinoma: a 12-year nationwide

follow-up study. _Medicine (Baltimore)_ 93, e52 (2014). Article  PubMed  Google Scholar  * Barlow, L. J., Korets, R., Laudano, M., Benson, M. & McKiernan, J. Predicting renal functional

outcomes after surgery for renal cortical tumours: a multifactorial analysis. _BJU Int._ 106, 489–492 (2010). Article  PubMed  Google Scholar  * Jeon, H. G., Jeong, I. G., Lee, J. W., Lee,

S. E. & Lee, E. Prognostic factors for chronic kidney disease after curative surgery in patients with small renal tumors. _Urology_ 74, 1064–1068 (2009). Article  PubMed  Google Scholar

  * Li, L. et al. Risk of chronic kidney disease after cancer nephrectomy. _Nat. Rev. Nephrol._ 10, 135–145 (2014). Article  PubMed  Google Scholar  * Cho, A. et al. Post-operative acute

kidney injury in patients with renal cell carcinoma is a potent risk factor for new-onset chronic kidney disease after radical nephrectomy. _Nephrol. Dial. Transplant._ 26, 3496–3501 (2011).

Article  PubMed  Google Scholar  * Lam, A. Q. & Humphreys, B. D. Onco-nephrology: AKI in the cancer patient. _Clin. J. Am. Soc. Nephrol._ 7, 1692–1700 (2012). Article  CAS  PubMed 

PubMed Central  Google Scholar  * Gallieni, M. et al. Acute kidney injury in cancer patients. _Contrib. Nephrol._ 13, 137–148 (2018). Article  Google Scholar  * Cosmai, L. et al. Opening an

onconephrology clinic: recommendations and basic requirements. _Nephrol. Dial. Transplant._ 33, 1503–1510 (2018). THIS PAPER DISCUSSES THE REQUIREMENTS NEEDED TO RUN AN ONCO-NEPHROLOGY

CLINIC AS WELL AS ITS FIELD OF INTEREST. Article  PubMed  Google Scholar  * Taylor, A. T. Radionuclides in nephrourology, part 2: pitfalls and diagnostic applications. _Nucl. J. Med._ 55,

786–798 (2014). Article  CAS  Google Scholar  * Srigley, J. R. et al. Protocol for the examination of specimens from patients with invasive carcinoma of renal tubular origin. _Arch. Pathol.

Lab. Med._ 134, e25–e30 (2010). Article  PubMed  Google Scholar  * Algaba, F. et al. Handling and reporting of nephrectomy specimens for adult renal tumors: a survey by the European Network

of Uropathology. _J. Clin. Pathol._ 65, 106–113 (2012). Article  PubMed  Google Scholar  * Gupta, S. et al. Safety and efficacy of molecularly targeted agents in patients with metastatic

kidney cancer with renal dysfunction. _Anticancer Drugs._ 22, 794–800 (2011). Article  CAS  PubMed  PubMed Central  Google Scholar  * Nouhaud, F. X. et al. Baseline chronic kidney disease is

associated with toxicity and survival in patients treated with targeted therapies for metastatic renal cell carcinoma. _Anticancer Drugs._ 26, 866–871 (2015). Article  CAS  PubMed  Google

Scholar  * Zabor, E. C. et al. Factors associated with recovery of renal function following radical nephrectomy for kidney neoplasm. _Clin. J. Am. Soc. Nephrol._ 11, 101–107 (2016). Article

  CAS  PubMed  Google Scholar  * 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  PubMed  PubMed Central  Google Scholar  * Calvo, E. et al. Improvement in survival end points of patients with metastatic renal cell carcinoma through sequential

targeted therapy. _Cancer Treat. Rev._ 50, 109–117 (2016). Article  PubMed  Google Scholar  * Escudier, B. et al. Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis,

treatment and follow-up. _Ann. Oncol._ 27 (Suppl. 5), v58–v68 (2016). Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS REVIEWER INFORMATION _Nature Reviews

Nephrology_ thanks H. Hammers, M. H. Rosner and the other anonymous reviewer(s) for their contribution to the peer review of this work. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Department of Internal Medicine, University of Pavia, Pavia, Italy Camillo Porta * Division of Translational Oncology, I.R.C.C.S. Istituti Clinici Scientifici Maugeri, Pavia, Italy Camillo

Porta * Division of Nephrology, A.S.S.T. Santi Paolo e Carlo, San Carlo Borromeo Hospital, Milan, Italy Laura Cosmai & Maurizio Gallieni * Department of Urology, Mayo Clinic, Rochester,

MN, USA Bradley C. Leibovich * Barts Cancer Institute Experimental Medicine Centre, Queen Mary University of London St Bartholomew’s Hospital, London, UK Thomas Powles * Department of

Clinical and Biomedical Sciences “Luigi Sacco”, University of Milan, Milan, Italy Maurizio Gallieni * Department of Urology, Netherlands Cancer Institute, Amsterdam, Netherlands Axel Bex

Authors * Camillo Porta View author publications You can also search for this author inPubMed Google Scholar * Laura Cosmai View author publications You can also search for this author

inPubMed Google Scholar * Bradley C. Leibovich View author publications You can also search for this author inPubMed Google Scholar * Thomas Powles View author publications You can also

search for this author inPubMed Google Scholar * Maurizio Gallieni View author publications You can also search for this author inPubMed Google Scholar * Axel Bex View author publications

You can also search for this author inPubMed Google Scholar CONTRIBUTIONS All authors researched the data, contributed to discussions of the content, wrote the article and reviewed or edited

the manuscript before submission. CORRESPONDING AUTHOR Correspondence to Camillo Porta. ETHICS DECLARATIONS COMPETING INTERESTS C.P. and A.B. contributed to the European Medicines Agency

(EMA) Committee for Medicinal Products for Human Use (CHMP) discussion regarding approval of sunitinib as an adjuvant treatment for resected renal cell carcinoma. The other authors declare

no competing interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Porta, C., Cosmai, L., Leibovich, B.C. _et al._ The

adjuvant treatment of kidney cancer: a multidisciplinary outlook. _Nat Rev Nephrol_ 15, 423–433 (2019). https://doi.org/10.1038/s41581-019-0131-x Download citation * Published: 26 March 2019

* Issue Date: July 2019 * DOI: https://doi.org/10.1038/s41581-019-0131-x SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link

Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative