Sorveglianza attiva e trattamenti mini-invasivi

2. Sorveglianza attiva e trattamenti mini-invasivi Vincenzo Ficarra Dipartimento di Scienze Sperimentali Mediche e Cliniche – Clinica di Urologia, Università degli Studi di Udine

3. Active Surveillance • Active surveillance is defined as the initial monitoring of tumour size by serial abdominal imaging (ultrasound, CT, or MRI) with delayed intervention reserved for those tumours that show clinical progression during follow-up • Active surveillance is a reasonable option for elderly and/or comorbid patients with small renal masses and limited life expectancy Ljungberg B. et al. EAU Guidelines, 2013

5. Active Surveillance Lane B. et al. Curr Opin Urol 2012; 22: 353-59

6. Active Surveillance • SRMs less than 3 cm are very unlikely to metastasize and deferring treatment has not been associated with increased failure to cure. • Active surveillance is a reasonable initial strategy in most patients with SRMs, particularly those with limited life-expectancy and increased perioperative risk. • Intervention should be considered for growth to greater • than 3–4 cm or by greater than 0.4–0.5 cm/year while on • active surveillance. Lane B. et al. Curr Opin Urol 2012; 22: 353-59

7. Active Surveillance Pooledanalysiscomparingpatientswho did not progress to metastasis and patients who demonstrated evidence of Progression at follow-up (33.5 months) Smaldone MC et al. Cancer 2012; 118: 997-1006

8. Active Surveillance • A substantial proportion of small renal masses remained radiographically static after an initial period of active surveillance • Progression to metastases occurred in a small percentage of patients and generally was a late event • Patients who have competing health risks, radiographic surveillance may be an acceptable initial approach, and delayed intervention may be reserved for patients who have tumors that exhibit significant linear or volumetric growth. Smaldone MC et al. Cancer 2012; 118: 997-1006

9. Active Surveillance with follow-up longerthan 5 years • 15 clear cell RCC and 2 papillary RCC • Median follow-up was 77.1 months • Median growth rate was 0.15 cm/y. • 2 (11%) required delayed intervention. • No metastases or cancer-related deaths occurred Haramis G et al. Urology 2011; 77: 787-791

10. Surveillanceprotocols • A definite protocol for ‘active’ surveillance of SRMs • has yet to be defined • A suggested approach consists to alternate between US and cross-sectional (CT or magnetic resonance) imaging (some would argue that the inconsistency in size estimates using multiple modalities is a weakness of this approach) • Imaging interval: every 3months for 1 year, every 6 months for the second year, and annually thereafter. Lane B. et al. Curr Opin Urol 2012; 22: 353-59

11. Indications for Ablative Therapies

12. Oncological aim of ablative technology • Ablative technology must be able to completlydestroyallviabletissue, with no area of viabletissueleft • The surgeon must be able to monitor and precisely target the area to be ablated to assure complete tumourdestrucion • Lowmorbidity

13. Autorino R et al. UrolOncol 2012; 30: 20-27

14. Mechanisms of Cryoablation Renal tumour (- 40 °C) Normal renal tissue (- 19.4 °C)

15. Cryoablation approaches • Laparoscopic Cryoablation (LCA) • - general anaesthesia mandatory • Percutaneous Cryoablation (PCA) • - MRI guided (reported under GA) • - CT guided (reported under sedation)

16. Laparoscopic Cryoablation (LCA) • Transperitoneal • - anterior renal mass • Retroperitoneal • - posterior renal mass

17. Percutaneous Cryoablation (PCA) CT guided MRI guided

18. Cryoablation approaches

19. Mechanisms of Radiofrequency Ablation (RFA) • Heat based ablative technique • High-frequency alternating current emitted through electrode placed within targeted tissue • T° > 60° C with denaturation of proteins; melting of cell membranes, loss of enzymatic function, destruction of cytoplasm

20. Radiofrequency Ablation (RFA): Approaches • Laparoscopic Radiofrency Ablation (LRFA) • - general anaesthesia mandatory • Percutaneous Radiofrequency Ablation (PRFA) • - MRI guided (reported under GA) • - CT guided (reported under sedation)

21. RFA: Image guidance and ablation monitoring • US: limited use • CT: used • - limitation in the detection of residual tumour in the same session • MRI: currently the best • - allows re-treatment of residual tumour in the same session

22. Radiofrequency Ablation (RFA): Percutaneous Approach

23. Radiofrequency Ablation (RFA): Tumour “skipping” • Persistence of viable tumour • cells within RFA-treated renal • masses • Are all these skipped lesion going to cause tumour recurrence ? • (?) Fixation effect of RF • energy Weld KJ et al. BJU Inter 2005; 96: 1224-1229 Aron M, Gill IS. Eur Urol 2007; 51: 348-357

24. Alternative Treatments: Follow-up and outcomes • Radiographic follow-up (CT scan or MRI) • - enhancement on post-contrast imaging • is considered evidence of incompletely • treated disease • - Grossly viable disease • Percutaneous biopsies • - viable tumour may be present despite a • lack of radiographic enhancement • - microscopic disease Kunkle DA et al J Urol 2008; 179: 1227-1234

25. Cryoablation: meta-analysis of case series studies (efficacy 89%) Successfullytreatedtumour was defined as no growth or no evidence of recurrence on CT scan or MRI ElDib C. et al. BJU Inter 2012; 110: 510-516

26. Cryoablation: meta-analysis of case series studies (complications 20%) ElDib C. et al. BJU Inter 2012; 110: 510-516

27. Cryoablation: functional outcomes Autorino R et al. UrolOncol 2012; 30: 20-27

28. RFA: meta-analysis of case series studies (efficacy 90%) Successfullytreatedtumour was defined as no growth or no evidence of recurrence on CT scan or MRI ElDib C. et al. BJU Inter 2012; 110: 510-516

29. RFA: meta-analysis of case series studies (complications 19%) ElDib C. et al. BJU Inter 2012; 110: 510-516

30. Complications after ablative therapies for small renal tumors Atwell TD et al. J VascIntervRadiol 2012; 23: 48-54

31. Alternative Treatments: Radiofrequency or Cryoablation Meta-Analysis of studies published between 1980 to 2006 Kunkle DA et al J Urol 2008; 179: 1227-1234

32. Alternative Treatments: Radiofrequency or Cryoablation Meta-Analysis of studies published between 1980 to 2006 Kunkle DA et al J Urol 2008; 179: 1227-1234

33. Alternative Treatments: Differences in clinical application * Patient’s age(Yrs) * * *p < 0.05 Kunkle DA et al J Urol 2008; 179: 1227-1234

34. Alternative Treatments: Differences in clinical application Tumour size (cm) * * *p < 0.05 Kunkle DA et al J Urol 2008; 179: 1227-1234

35. Alternative Treatments: Differences in clinical application Follow-up (months) * * * *p < 0.05 Kunkle DA et al J Urol 2008; 179: 1227-1234

36. Alternative Treatments: Pathological confirmation of SRM Kunkle DA et al J Urol 2008; 179: 1227-1234

37. Local recurrence-free survival Statistically significant differences (p < 0.05): LPN, OPN, LRN, and ORN rates are statistically indistinguishable and are all significantly higher than Cryo and RFA rates; Cryo and RFA rates are statistically indistinguishable Campbell S et al J Urol 2009; 182: 1271-79

38. Ablative therapies Vs surgery Faddegon S. et al. UrolClin North Am 2012; 39: 181-190

39. Cryoablation: future perspectives Autorino R et al. UrolOncol 2012; 30: 20-27