The overall 5-year survival is around 78%, but this depends largely on stage at diagnosis, as well as on established prognostic factors.[19]National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. Cancer stat facts: kidney and renal pelvis cancer. 2024 [internet publication].
https://seer.cancer.gov/statfacts/html/kidrp.html
Five-year relative survival by stage at diagnosis (kidney and renal pelvis cancer, 2014-2020 data):[19]National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. Cancer stat facts: kidney and renal pelvis cancer. 2024 [internet publication].
https://seer.cancer.gov/statfacts/html/kidrp.html
Localized 93.3%
Regional 75.1%
Distant 18.2%
The advent of targeted treatments and immune checkpoint inhibition for advanced disease is continuing to improve the outlook for RCC. Patients who experience symptoms on presentation have poorer prognosis.[16]Kawaciuk I, Hyrsl L, Dusek P, et al. Influence of tumour-associated symptoms on the prognosis of patients with renal cell carcinoma. Scand J Urol Nephrol. 2008;42(5):406-11.
http://www.ncbi.nlm.nih.gov/pubmed/18932106?tool=bestpractice.com
Prognosis is particularly poor in those who develop paraneoplastic syndromes.[18]Sacco E, Pinto F, Sasso F, et al. Paraneoplastic syndromes in patients with urological malignancies. Urol Int. 2009;83(1):1-11.
https://www.karger.com/Article/Pdf/224860
http://www.ncbi.nlm.nih.gov/pubmed/19641351?tool=bestpractice.com
Tumor histology subtypes can indicate varying prognoses, but when adjusted for stage and tumor grade, this may become less relevant. Clear-cell histology may, in general, be associated with poorer prognosis; in addition, sarcomatoid differentiation in any histology tends to dictate a more aggressive tumor.[37]Warren AY, Harrison D. WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies. World J Urol. 2018 Dec;36(12):1913-26.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280811
http://www.ncbi.nlm.nih.gov/pubmed/30123932?tool=bestpractice.com
Overall, pathologic and clinical staging, as well as certain patient characteristics, are included in prognostic models.
Prognostic models
RCC is diagnosed by a combination of imaging and pathology to confirm malignancy, and to stage patients both clinically and pathologically.[7]Amin MB, Edge S, Green F, et al. AJCC cancer staging manual. 8th ed. (2017). Cham, Switzerland: Springer International; 2017.[8]Brierley JD, Gospodarowicz MK, Wittekind C, eds. Union for International Cancer Control. TNM classification of malignant tumors. 8th ed. Chichester: Wiley-Blackwell; 2017. Prognostic models have been developed to integrate these diagnostic findings into a schema that includes other patient factors, and that may better predict for survival or prognosis than classic staging.[74]Zisman A, Pantuck AJ, Dorey F, et al. Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol. 2001 Mar 15;19(6):1649-57.
http://www.ncbi.nlm.nih.gov/pubmed/11250993?tool=bestpractice.com
[75]Frank I, Blute ML, Cheville JC, 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. 2002 Dec;168(6):2395-400.
http://www.ncbi.nlm.nih.gov/pubmed/12441925?tool=bestpractice.com
[77]Heng DY, Xie W, Regan MM, et al. External validation and comparison with other models of the
International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013 Feb;14(2):141-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144042
http://www.ncbi.nlm.nih.gov/pubmed/23312463?tool=bestpractice.com
The effort to integrate molecular profiling and biomarkers into prognostic models continues.
The UCLA Integrated Staging System and SSIGN (Mayo) algorithms can be applied to patients with early localized disease, postnephrectomy.[74]Zisman A, Pantuck AJ, Dorey F, et al. Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol. 2001 Mar 15;19(6):1649-57.
http://www.ncbi.nlm.nih.gov/pubmed/11250993?tool=bestpractice.com
[75]Frank I, Blute ML, Cheville JC, 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. 2002 Dec;168(6):2395-400.
http://www.ncbi.nlm.nih.gov/pubmed/12441925?tool=bestpractice.com
The Memorial Sloan Kettering Cancer Center (MSKCC) model is one of the more widely used prognostic models in metastatic disease, and has been well validated.[60]Motzer RJ, Bacik J, Mazumdar M. Prognostic factors for survival of patients with stage IV renal cell carcinoma: Memorial Sloan-Kettering Cancer Center experience. Clin Cancer Res. 2004 Sep 15;10(18 Pt 2):6302S-3S.
http://clincancerres.aacrjournals.org/content/10/18/6302S.long
http://www.ncbi.nlm.nih.gov/pubmed/15448021?tool=bestpractice.com
Further prognostic criteria for patients with metastatic RCC treated with sunitinib, sorafenib, and bevacizumab have been elucidated, in addition to validation of some of the MSKCC criteria.[76]Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009 Dec 1;27(34):5794-9.
http://www.ncbi.nlm.nih.gov/pubmed/19826129?tool=bestpractice.com
This study found that hemoglobin less than the lower limit of normal, corrected calcium greater than the upper limit of normal (ULN), Karnofsky performance status less than 80%, time from original diagnosis to treatment of less than 1 year, 2 or more organ sites of metastatic disease, neutrophils greater than the ULN, and platelets greater than the ULN were independent adverse prognostic factors.[76]Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009 Dec 1;27(34):5794-9.
http://www.ncbi.nlm.nih.gov/pubmed/19826129?tool=bestpractice.com
Patients were segregated into three risk categories: favorable-risk group (no prognostic factors), in which median overall survival (mOS) was not reached and 2-year OS (2y OS) was 75%; intermediate-risk group (1 or 2 prognostic factors), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (3 to 6 prognostic factors), in which mOS was 8.8 months and 2y OS was 7%.[76]Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009 Dec 1;27(34):5794-9.
http://www.ncbi.nlm.nih.gov/pubmed/19826129?tool=bestpractice.com
The other most commonly used risk stratification score is the International Metastatic Renal Cell Carcinoma Database Consortium criteria, which includes neutrophilia and thrombocytosis. Predictors of poor survival are:
Karnofsky performance status of less than 80%
Less than 1 year from diagnosis to treatment
Anemia (hemoglobin concentration less than the lower limit of normal)
Hypercalcemia (corrected calcium concentration greater than the ULN)
Neutrophilia (neutrophil count greater than the ULN)
Thrombocytosis (platelet count greater than the ULN).[77]Heng DY, Xie W, Regan MM, et al. External validation and comparison with other models of the
International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol. 2013 Feb;14(2):141-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144042
http://www.ncbi.nlm.nih.gov/pubmed/23312463?tool=bestpractice.com
Early-stage RCC prognosis
Early-stage disease in general has excellent prognosis, with greater than 95% cancer-specific survival among all management strategies (median follow-up 22 to 120 months).[4]Jewett MA, Zuniga A. Renal tumor natural history: the rationale and role for active surveillance. Urol Clin North Am. 2008 Nov;35(4):627-34; vii.
http://www.ncbi.nlm.nih.gov/pubmed/18992616?tool=bestpractice.com
Increasing age, larger tumor size and higher tumor grade were the most common predictors of worse cancer-specific survival.[88]Pierorazio PM, Johnson MH, Patel HD, et al. Management of renal masses and localized renal cancer: systematic review and meta-analysis. J Urol. 2016 Oct;196(4):989-99.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593254
http://www.ncbi.nlm.nih.gov/pubmed/27157369?tool=bestpractice.com
Risk of local relapse after adequate curative surgery for small renal tumors is rare (up to 2%) and is unlikely after 5 years.[174]Donat SM, Diaz M, Bishoff JT, et al. Follow-up for clinically localized renal neoplasms: AUA guideline. J Urol. 2013 Aug;190(2):407-16.
https://www.auajournals.org/doi/10.1016/j.juro.2013.04.121
http://www.ncbi.nlm.nih.gov/pubmed/23665399?tool=bestpractice.com
However, between 20% to 30% of patients with localized disease who undergo curative surgery will develop recurrent or metastatic disease within 5 years.[175]Dabestani S, Marconi L, Kuusk T, et al. Follow-up after curative treatment of localised renal cell carcinoma. World J Urol. 2018 Dec;36(12):1953-59.
http://www.ncbi.nlm.nih.gov/pubmed/29767327?tool=bestpractice.com
Advanced stage/metastatic RCC prognosis
In one study in patients diagnosed with locally advanced disease, the 10-year progression-free survival for those with T3 clear cell tumors was 72%.[176]Bazzi WM, Sjoberg DD, Feuerstein MA, et al. Long-term survival rates after resection for locally advanced kidney cancer: Memorial Sloan Kettering Cancer Center 1989 to 2012 experience. J Urol. 2015 Jun;193(6):1911-6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439353
http://www.ncbi.nlm.nih.gov/pubmed/25524244?tool=bestpractice.com
The median overall survival of untreated metastatic disease is 5 months; this improved to 10.2 months in the cytokine era, and to 17.7 months when treated with targeted molecular therapy.[177]Gangadaran SGD. Current management options in metastatic renal cell cancer. Oncol Rev. 2017 Jun 14;11(2):339.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481727
http://www.ncbi.nlm.nih.gov/pubmed/28680539?tool=bestpractice.com
Specifically, evidence has demonstrated a near doubling of overall survival since the general availability of sunitinib for metastatic RCC.[178]Heng DY, Chi KN, Murray N, et al. A population-based study evaluating the impact of sunitinib on overall survival in the treatment of patients with metastatic renal cell cancer. Cancer. 2009 Feb 15;115(4):776-83.
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.24051
http://www.ncbi.nlm.nih.gov/pubmed/19127560?tool=bestpractice.com
The COMPARZ data from patients treated with pazopanib or sunitinib estimated median of favorable risk group at approximately 42 months, intermediate-risk group at approximately 26 months, and poor risk group at less than 1 year.[120]Motzer RJ, Hutson TE, Reeves J, et al. Randomized open-label phase III trial of pazopanib versus sunitinib in first-line treatment of patients with metastatic renal cell carcinoma (MRCC): results of the COMPARZ trial. ESMO Congress; October 1, 2012; Vienna. Abstract LBA8.
https://www.webges.com/cslide/library/esmo/mylibrary/search/session/0/370_135
The advent of immune checkpoint inhibitors and combinations of therapies has led to prolonged disease control in some patients and use of older median overall survival data is no longer completely applicable.[80]Calvo E, Porta C, Grünwald V, et al. The current and evolving landscape of first-line treatments for advanced renal cell carcinoma. Oncologist. 2019 Mar;24(3):338-48.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519762
http://www.ncbi.nlm.nih.gov/pubmed/30158285?tool=bestpractice.com
[179]Garje R, An J, Greco A, et al. The future of immunotherapy-based combination therapy in metastatic renal cell carcinoma. Cancers (Basel). 2020 Jan 7;12(1):143.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017064
http://www.ncbi.nlm.nih.gov/pubmed/31936065?tool=bestpractice.com
Metachronous metastases (recurrent metastatic disease diagnosed at a later time) fare better than synchronous metastases (metastases diagnosed in separate sites at the same time), and there is evidence to support repeat metastasectomy.[180]Hofmann HS, Neef H, Krohe K, et al. Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma. Eur Urol. 2005 Jul;48(1):77-81.
http://www.ncbi.nlm.nih.gov/pubmed/15967255?tool=bestpractice.com
Patients with the best prognoses are those with a long disease-free interval since original diagnosis (>12 months), R0 resections (no residual microscopic tumor cells remaining in tumor bed; surgical resection margins on pathology are completely negative [i.e., clear of tumor]), and no more than 6 metastases.[180]Hofmann HS, Neef H, Krohe K, et al. Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma. Eur Urol. 2005 Jul;48(1):77-81.
http://www.ncbi.nlm.nih.gov/pubmed/15967255?tool=bestpractice.com
[181]Kavolius JP, Mastorakos DP, Pavlovich C, et al. Resection of metastatic renal cell carcinoma. J Clin Oncol. 1998 Jun;16(6):2261-6.
http://www.ncbi.nlm.nih.gov/pubmed/9626229?tool=bestpractice.com
Survival at 5 years has been found to range from 30% to 50% in patients with resection of metastases for pulmonary lesions, and up to 33% at 10 years with pulmonary resections.[180]Hofmann HS, Neef H, Krohe K, et al. Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma. Eur Urol. 2005 Jul;48(1):77-81.
http://www.ncbi.nlm.nih.gov/pubmed/15967255?tool=bestpractice.com
[181]Kavolius JP, Mastorakos DP, Pavlovich C, et al. Resection of metastatic renal cell carcinoma. J Clin Oncol. 1998 Jun;16(6):2261-6.
http://www.ncbi.nlm.nih.gov/pubmed/9626229?tool=bestpractice.com
[182]Piltz S, Meimarakis G, Wichmann MW, et al. Long-term results after pulmonary resection of renal cell carcinoma metastases. Ann Thorac Surg. 2002 Apr;73(4):1082-7.
http://www.ncbi.nlm.nih.gov/pubmed/11996245?tool=bestpractice.com