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Prognostic factors and predictive models

Prognostic factors and predictive models. Vincenzo Ficarra Associate Professor of Urology, University of Padova, Italy Scientific Director OLV Robotic Surgery Institute, Aalst, Belgium. RCC Prognostic Factors. Kidney Cancer. Clinical Laboratory ? Bioptical. Localized. Metastatic.

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Prognostic factors and predictive models

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  1. Prognostic factors and predictive models Vincenzo Ficarra Associate Professor of Urology, University of Padova, Italy Scientific Director OLV Robotic Surgery Institute, Aalst, Belgium

  2. RCC Prognostic Factors Kidney Cancer Clinical Laboratory ? Bioptical Localized Metastatic Surgery Medical therapies Pathological Molecular Cytogenetic Clinical Laboratory

  3. RCC Oncologic Outcomes PFS Local/Distant recurrence Localized OS CSS RFS Death Kidney cancer Diagnosis Metastatic Disease PFS

  4. Role of Integrated staging systems in non-metastatic RCC • Postoperative counseling • Postoperative surveillance protocols • Definition of selectioncriteria for ongoing • adjuvant trials

  5. Clinical Prognostic Factors • Age • Gender • Performance Status • Mode of presentation (Symptoms) • Clinical tumour size • Clinical staging (cTNM)

  6. Performance Status ECOG Karakiewicz P., Ficarra V. et al. Eur J Cancer 2007; 43: 1023-29

  7. Mode of presentation Karakiewicz P., Ficarra V. et al. Eur J Cancer 2007; 43: 1023-29

  8. Models predicting recurrence after NT:Preoperative parameters Symptoms Clinical size Symptoms Clinical size Gender Clinical size Symptoms Nodes (Imaging) Necrosis (imaging)

  9. Models predicting survival after NT:Preoperative parameters Accuracy: 84-88% (external) Karakiewicz P. et al. Eur Urol 2009; 55: 287-295

  10. Preop. Karakiewicznomogram (3364 pts) c index (1 year) 87.8 (84.4-91.4) c index (2 yrs) 87 (84.4-89.5) c index (5 yrs) 84 (82.3-87.1) c index (10 yrs) 85.9 (83.2-88.6) Gontero P. and SATURN Project members (submitted to BJU Intern)

  11. Models predicting survival after NT:Preoperative parameters Accuracy: 70-73% (external) Kutikov A. et al. J Clin Oncol 2009; 28: 311-317

  12. Pathologic Prognostic Factors • Tumour extension (TNM) • Tumour size • Histologic Subtypes • Grading • Necrosis • Sarcomatoid de-differentiation • Microvascular invasion

  13. Evolution of the TNM staging system for organ-confined RCC TNM, 1997 TNM, 2002 TNM, 2009 T1  7 cm T1a  4 cm  4 cm T1b > 4 - 7 cm > 4 - 7 cm T2 > 7 cm > 7 cm T2a > 7 - ≤ 10 cm T2b > 10 cm

  14. TNM, 2009 Version – Why ? 544 patients with unilateral, sporadic pT2 RCC treated with radical nephrectomy or nephron sparing surgery between 1970 and 2000 Frank I et al. J. Urol. 2005; 173: 380-384

  15. Validation of the 2009 TNM version 5,339 patients with RCC surgically treated between 1997 and 2007 Novara G et al. Eur Urol 2010; 58: 588-95

  16. Validation of the 2009 TNM version Waalkes S et al. Eur. Urol. 2011; 59: 258-263

  17. Development of the TNM staging system for locally advanced RCC TNM, 2002 TNM, 2009 T3a Fat and adrenal invasion Fat invasion orV1 T3b V1 – V2 V2 T3c V3 V3 T4 Outside Gerota’s fascia Outside Gerota’s fascia and adrenal invasion

  18. Validation of the 2009 TNM version 5,339 patients with RCC surgically treated between 1997 and 2007 Novara G et al. Eur Urol 2010; 58: 588-95

  19. Redefining pT3 RCC: Fat invasion + Venous involvement V1 V2 V1+fat inv V2+fat inv V1-2+adrenal inv

  20. Redefining pT3 RCC: Fat invasion + Venous involvement Margulis V. et al. Cancer 2007; 109: 2439-44

  21. Clear Cell Papillary Chromophobe Oncocitoma

  22. RCC with prominent leiomyomatous proliferation clear cell papillary RCC Tubulocystic RCC Oncocytic papillary RCC

  23. Prognostic Value of Histologic Subtypes Capitanio U. et al BJU Inter 2008: 103: 1496-1500

  24. Prognostic Value of Histologic Subtypes Capitanio U. et al BJU Inter 2008: 103: 1496-1500

  25. Histologic Subtypes and definition of other histologic factors

  26. Fuhrman Nuclear Grading Grade 1 Grade 2 Grade 3 Grade 4

  27. Fuhrman nuclear grading 14,064 cases (clear cell RCC) Sun M. et al Eur Urol 2009; 56: 775

  28. Nucleolar Grade but not Fuhrman Grade Is applicable to Papillary RCC Sika D et al Am J Surg Pathol. 2006 Sep;30(9):1091-6.

  29. Fuhrman nuclear grading in papillary RCC Nuclear grading Nucleolar grading Klatte T et al J Urol. 2010; 183: 2143-2147

  30. A novel tumor grading scheme for Chromophobe Renal Cell Carcinoma Paner et al Am J Surg Pathol. 2010; 34: 1233-1240

  31. Prognostic Value of Coagulative necrosis in clear cell Sengupta S. et al Cancer 2005; 104: 511-520

  32. Prognostic Value of Coagulative necrosis in clear cell Klatte T. et al J Urol 2009; 181: 1558-64

  33. Prognostic Value of Coagulative necrosis in papillary RCC Sengupta S. et al Cancer 2005; 104: 511-520

  34. Prognostic Value of Coagulative necrosis in papillary RCC Klatte T. et al Clin Cancer Res 2009; 15: 1162

  35. Prognostic Value of Coagulative necrosis in chromophobe RCC Independent predictors of aggressive chromophobe RCC Amin MB et al Am J Clin Surg Pathol 2008; 32: 1822-34

  36. Prognostic Value of Sarcomatoiddedifferentiation

  37. Prognostic Value of Sarcomatoiddedifferentiation Cheville JC et al Am J Surg Pathol 2004; 28: 435-441

  38. Models predicting recurrence after NT:Postoperative parameters Accuracy: 74% (internal) - 61-84% (external) Kattan M. et al J Urol 2001; 166: 63-67

  39. Models predicting recurrence after NT:Postoperative parameters Accuracy: 75-81% (external) Zisman A. et al JCO 2002; 20: 4559-4566 Cindolo L., Ficarra V., et al Cancer 2005; 104: 1362-1371

  40. Models predicting recurrence after NT:Postoperative parameters Accuracy: 82% (internal) – 78-79% (external) Sorbellini M. et al J Urol 2005; 173: 48-51

  41. Models predicting recurrence after NT:Postoperative parameters Accuracy: 84% (internal) – 80% (external) • T stage (TNM, 2002) Score • - pT1a 0 • - pT1b 2 • - pT2 3 • - pT3-4 4 • N stage • - pNx-pN0 0 • - pN1-2 2 • Tumor Size Score • - less than 10 cm 0 • - 10 or greater 1 • Nuclear Grade • - Grade 1-2 0 • - Grade 3 1 • - Grade 4 3 • Necrosis • - absent 0 • - present 1 Leibovich B. et al Cancer 2003; 97: 1663-71

  42. Stage, Size, Grade and Necrosis (SSGN) Score e RFS (0-2) (3-5) (> 6) Leibovich B. et al Cancer 2003; 97: 1663-71

  43. Adjuvant therapy in RCC: planned trials

  44. Models predicting survival after NT:Postoperative parameters N0/M0 N+/M+ Zisman A. et al JCO 2002; 20: 4559-4566

  45. External validation of the UCLA Integrated Staging System 3,199 confined RCC and 1,083 metastatic RCC C index: 0.765 – 0.863 C index: 0.584 – 0.776 Patard JJ, Ficarra V. et al JCO 2004; 22: 3316-3322

  46. Models predicting survival after NT:Postoperative parameters (SSGN) Score accuracy: 75-88% (external) • T stage (TNM, 1997) Score • - pT1 0 • - pT2 1 • - pT3a-b-c 2 • - pT4 0 • N stage • - pNx-pN0 0 • - pN1-2 2 • M stage • - M0 0 • - M1 4 • Tumor Size Score • - less than 5 cm 0 • - 5 or greater 2 • Nuclear Grade • - Grade 1-2 0 • - Grade 3 1 • - Grade 4 3 • Necrosis • - absent 0 • - present 2 Frank I et al 2002; 168: 2395-2400

  47. External validation of the SSIGN Score (slides revision) Concordance index: 0.88 Ficarra V., Martignoni G. et al J Urol 2006; 175: 1235-1239

  48. Models predicting survival after NT:Postoperative parameters Accuracy: 75-89% (external) Karakiewicz P., Ficarra V. et al JCO 2007; 25: 1316-1322

  49. Molecular markers for RCC Belldegrun As et al Eur Urol Suppl 2007; 6: 477-483

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