Prognostic factors and prognostic models for renal cell carcinoma: a literature review

PurposeFollowing curative treatment for localised renal cell carcinoma (RCC), up to 30% of patients develop tumour recurrence. Prognostic scores are essential to guide individualised surveillance protocols, patient counselling and potentially in the future to guide adjuvant therapy. In metastatic RCC, prognostic scores are routinely used for treatment selection in clinical practice as well as in all major trials.MethodsWe performed a literature review on the current evidence based on prognostic factors and models for localised and metastatic RCC.ResultsA number of prognostic factors have been identified, of which tumour node metastasis classification remains the most important. Multiple prognostic models and nomograms have been developed for localised disease, based on a combination of tumour stage, grade, subtype, clinical features, and performance status. However, there is poor level of evidence for their routine use. Prognostic scores for patients with metastatic RCC receiving targeted treatments are used routinely, but have limited accuracy. Molecular markers can improve the accuracy of established prognostic models, but frequently lack external, independent validation.ConclusionSeveral factors and models predict prognosis of localised and metastatic RCC. They represent valuable tools to provide estimates of clinically important endpoints, but their accuracy should be improved further. Validation of molecular markers is a future research priority.

[1]  Hai Huang,et al.  Microvascular invasion as a prognostic indicator in renal cell carcinoma: a systematic review and meta-analysis. , 2015, International journal of clinical and experimental medicine.

[2]  L. Bostad,et al.  A prospective risk-stratified follow-up programme for radically treated renal cell carcinoma patients: evaluation after eight years of clinical use , 2016, World Journal of Urology.

[3]  J. Cheville,et al.  The International Society of Urological Pathology (ISUP) Grading System for Renal Cell Carcinoma and Other Prognostic Parameters , 2013, The American journal of surgical pathology.

[4]  P. Humphrey,et al.  The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. , 2016, European urology.

[5]  A. Belldegrun,et al.  Molecular Signatures of Localized Clear Cell Renal Cell Carcinoma to Predict Disease-Free Survival after Nephrectomy , 2009, Cancer Epidemiology Biomarkers & Prevention.

[6]  A. Shalhav,et al.  Clinically localized type 1 and 2 papillary renal cell carcinomas have similar survival outcomes following surgery , 2016, World Journal of Urology.

[7]  J. Patard,et al.  Multi-institutional validation of a new renal cancer-specific survival nomogram. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  Recognizing the Continuous Nature of Expression Heterogeneity and Clinical Outcomes in Clear Cell Renal Cell Carcinoma , 2017, Scientific Reports.

[9]  K. Bensalah,et al.  European Association of Urology Guidelines Regarding Adjuvant Therapy for Renal Cell Carcinoma , 2016 .

[10]  T. Klatte,et al.  Microvascular and lymphovascular tumour invasion are associated with poor prognosis and metastatic spread in renal cell carcinoma: a validation study in clinical practice , 2018, BJU international.

[11]  N. Rioux-Leclercq,et al.  Prognostic ability of simplified nuclear grading of renal cell carcinoma , 2007, Cancer.

[12]  A. Belldegrun,et al.  Pathobiology and prognosis of chromophobe renal cell carcinoma. , 2008, Urologic oncology.

[13]  J. Lam,et al.  Postoperative surveillance protocol for patients with localized and locally advanced renal cell carcinoma based on a validated prognostic nomogram and risk group stratification system. , 2005, The Journal of urology.

[14]  P. Russo,et al.  Histologic subtype impacts cancer-specific survival in patients with sarcomatoid-variant renal cell carcinoma treated surgically , 2016, World Journal of Urology.

[15]  E. Steyerberg,et al.  Prognosis Research Strategy (PROGRESS) 3: Prognostic Model Research , 2013, PLoS medicine.

[16]  J. Cheville,et al.  Histologic coagulative tumor necrosis as a prognostic indicator of renal cell carcinoma aggressiveness , 2005, Cancer.

[17]  M. Kattan,et al.  A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma. , 2005, The Journal of urology.

[18]  Pierre I Karakiewicz,et al.  Prognostic factors and predictive models in renal cell carcinoma: a contemporary review. , 2011, European urology.

[19]  T. Klatte,et al.  Preoperative serum cholesterol is an independent prognostic factor for patients with renal cell carcinoma (RCC) , 2015, BJU international.

[20]  Amnon Zisman,et al.  Cytogenetic and Molecular Tumor Profiling for Type 1 and Type 2 Papillary Renal Cell Carcinoma , 2009, Clinical Cancer Research.

[21]  Andrew J Vickers,et al.  Everything you always wanted to know about evaluating prediction models (but were too afraid to ask). , 2010, Urology.

[22]  Prognostic value of the Glasgow Prognostic Score in renal cell carcinoma: a meta-analysis , 2017, World Journal of Urology.

[23]  Shenglin Ma,et al.  Prognostic value of preoperative NLR, dNLR, PLR and CRP in surgical renal cell carcinoma patients , 2017, World Journal of Urology.

[24]  J. Cheville,et al.  Paraneoplastic syndromes are associated with adverse prognosis among patients with renal cell carcinoma undergoing nephrectomy , 2016, World Journal of Urology.

[25]  R. Body,et al.  Protocol for a multicentre randomised feasibility STUdy evaluating the impact of a prognostic model for Management of BLunt chest wall trauma patients: STUMBL trial , 2017, BMJ Open.

[26]  David B Seligson,et al.  Hypoxia-Inducible Factor 1α in Clear Cell Renal Cell Carcinoma , 2007, Clinical Cancer Research.

[27]  M. Bains,et al.  The Prognostic Impact of a Positive Vascular Margin in pT3 Clear Cell Renal Cell Carcinomas , 2015 .

[28]  Marco Borghesi,et al.  Positive surgical margins after nephron-sparing surgery for renal cell carcinoma: incidence, clinical impact, and management. , 2013, Clinical genitourinary cancer.

[29]  Sylvie Négrier,et al.  Imaging , Diagnosis , Prognosis Prognostic Model for Survival in Patients with Metastatic Renal Cell Carcinoma : Results from the International Kidney Cancer Working Group , 2011 .

[30]  T. Choueiri,et al.  The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. , 2015, The Lancet. Oncology.

[31]  R. Figlin,et al.  Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  Lorenzo Marconi,et al.  EAU guidelines on renal cell carcinoma: 2014 update. , 2010, European urology.

[33]  Soonmyung Paik,et al.  Use of archived specimens in evaluation of prognostic and predictive biomarkers. , 2009, Journal of the National Cancer Institute.

[34]  J. Patard,et al.  A proposal for reclassification of the Fuhrman grading system in patients with clear cell renal cell carcinoma. , 2009, European urology.

[35]  P. Weibl,et al.  Validation of serum C‐reactive protein (CRP) as an independent prognostic factor for disease‐free survival in patients with localised renal cell carcinoma (RCC) , 2013, BJU international.

[36]  T. Jang,et al.  Advanced‐stage renal cell carcinoma treated by radical nephrectomy and adjacent organ or structure resection , 2009, BJU international.

[37]  T. Choueiri,et al.  External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. , 2013, The Lancet. Oncology.

[38]  A. Matakidou,et al.  Prognostic effect of cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma: a comparative study using inverse probability of treatment weighting , 2018, World Journal of Urology.

[39]  F. Algaba,et al.  Vimentin over-expression and carbonic anhydrase IX under-expression are independent predictors of recurrence, specific and overall survival in non-metastatic clear-cell renal carcinoma: a validation study , 2016, World Journal of Urology.

[40]  K. Ballman,et al.  Biomarker: Predictive or Prognostic? , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  C. Porta,et al.  Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project†. , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[42]  N. Rioux-Leclercq,et al.  Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  Margarita Lopatin,et al.  A 16-gene assay to predict recurrence after surgery in localised renal cell carcinoma: development and validation studies. , 2015, The Lancet. Oncology.

[44]  R. Figlin,et al.  Prognostic factors for progression-free and overall survival with sunitinib targeted therapy and with cytokine as first-line therapy in patients with metastatic renal cell carcinoma. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[45]  A. Harris,et al.  REporting recommendations for tumour MARKer prognostic studies (REMARK) , 2005, British Journal of Cancer.

[46]  V. Margulis,et al.  Can we better select patients with metastatic renal cell carcinoma for cytoreductive nephrectomy? , 2010, Cancer.

[47]  M. P. Laguna Re: A Prospective Risk-Stratified Follow-up Programme for Radically Treated Renal Cell Carcinoma Patients: Evaluation after Eight Years of Clinical Use , 2017 .

[48]  T. Klatte,et al.  200 Comparison of the prognostic value of pretreatment measurements of systemic inflammatory response in patients undergoing curative resection of clear cell renal cell carcinoma , 2015 .

[49]  W. Sauerbrei,et al.  Reporting of prognostic studies of tumour markers: a review of published articles in relation to REMARK guidelines , 2009, British Journal of Cancer.

[50]  Matteo Brunelli,et al.  Original and reviewed nuclear grading according to the Fuhrman system , 2005, Cancer.

[51]  Mark W. Ball,et al.  Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma , 2018, Science.

[52]  M. Galsky A prognostic model for metastatic renal-cell carcinoma. , 2013, The Lancet. Oncology.

[53]  J. Cheville,et al.  Prediction of progression after radical nephrectomy for patients with clear cell renal cell carcinoma , 2003, Cancer.

[54]  H. Kluger,et al.  Clinicopathological and immunohistochemical characteristics of papillary renal cell carcinoma with emphasis on subtyping. , 2015, Human pathology.

[55]  T. Klatte,et al.  The protease activated receptor 1 gene variation IVSn -14 A>T is associated with distant metastasis and cancer specific survival in renal cell carcinoma. , 2013, The Journal of urology.

[56]  M. Kattan,et al.  A postoperative prognostic nomogram for renal cell carcinoma. , 2001, The Journal of urology.

[57]  B. Delahunt,et al.  Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors. , 1997, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[58]  Gyan Bhanot,et al.  Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns. , 2010, Genes & cancer.

[59]  T. Choueiri,et al.  Prognostic factors associated with long-term survival in previously untreated metastatic renal cell carcinoma. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[60]  A. Belldegrun,et al.  Presence of tumor necrosis is not a significant predictor of survival in clear cell renal cell carcinoma: higher prognostic accuracy of extent based rather than presence/absence classification. , 2009, The Journal of urology.

[61]  K. Strimbu,et al.  What are biomarkers? , 2010, Current opinion in HIV and AIDS.

[62]  S. Hofbauer,et al.  Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma , 2014, British Journal of Cancer.

[63]  Alexander L. R. Lubbock,et al.  Carbonic Anhydrase 9 Expression Increases with Vascular Endothelial Growth Factor–Targeted Therapy and Is Predictive of Outcome in Metastatic Clear Cell Renal Cancer , 2014, European urology.

[64]  J. Cheville,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. , 2002, The Journal of urology.

[65]  William P. Parker,et al.  Predicting Oncologic Outcomes in Renal Cell Carcinoma After Surgery. , 2018, European urology.

[66]  A. Ravaud,et al.  Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Français d'Immunothérapie. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[67]  Wanling Xie,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. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  J. Manola,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 , 2016, The Lancet.

[69]  S. Fuhrman,et al.  Prognostic significance of morphologic parameters in renal cell carcinoma , 1982, The American journal of surgical pathology.

[70]  A. Ravaud,et al.  Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study , 2018, Clinical Cancer Research.

[71]  M. Kattan,et al.  ClearCode34: A prognostic risk predictor for localized clear cell renal cell carcinoma. , 2014, European urology.

[72]  S. Signoretti,et al.  Molecular Subtypes Improve Prognostic Value of International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Model. , 2017, The oncologist.

[73]  Michael P. Messenger,et al.  Prognostic utility of pre-operative circulating osteopontin, carbonic anhydrase IX and CRP in renal cell carcinoma , 2012, British Journal of Cancer.

[74]  K. Pummer,et al.  Validation of the pre-treatment neutrophil–lymphocyte ratio as a prognostic factor in a large European cohort of renal cell carcinoma patients , 2013, British Journal of Cancer.

[75]  J. Cheville,et al.  Loss of BAP1 protein expression is an independent marker of poor prognosis in patients with low‐risk clear cell renal cell carcinoma , 2014, Cancer.

[76]  T. Choueiri,et al.  Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. , 2014, European urology.

[77]  P. Tan,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. , 2010, Urology.

[78]  K. Bensalah,et al.  The subclassification of papillary renal cell carcinoma does not affect oncological outcomes after nephron sparing surgery , 2016, World Journal of Urology.

[79]  M Mazumdar,et al.  Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[80]  C. Mathers,et al.  Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 , 2015, International journal of cancer.

[81]  K. Chamie,et al.  Histopathology of surgically treated renal cell carcinoma: survival differences by subtype and stage. , 2012, The Journal of urology.

[82]  R. Motzer,et al.  Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[83]  William P. Parker,et al.  Application of the Stage, Size, Grade, and Necrosis (SSIGN) Score for Clear Cell Renal Cell Carcinoma in Contemporary Patients. , 2017, European urology.

[84]  David B Seligson,et al.  Prognostic relevance of the mTOR pathway in renal cell carcinoma , 2007, Cancer.