ablativi Vincenzo Ficarra Direttore Clinica di Urologia Azienda Ospedaliera Universitaria di Udine

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1 Sorveglianza attiva e trattamenti ablativi Vincenzo Ficarra Direttore Clinica di Urologia Azienda Ospedaliera Universitaria di Udine

2 Risk of mortality in RCC patients Kutikov A. et al. J Clin Oncol 2010; 28:

3 Cardiovascular and cancer death Patel HD. et al. BJU Inter 2014; (available online)

4 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, 2014

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

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 lifeexpectancy and increased perioperative risk. Intervention should be considered for growth to greater than 3 4 cm or by greater than cm/year while on active surveillance. Lane B. et al. Curr Opin Urol 2012; 22:

7 Surveillance protocols 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 3 months for 1 year, every 6 months for the second year, and annually thereafter Lane B. et al. Curr Opin Urol 2012; 22:

8 Indications for Ablative Therapies AUA, 2009 ESMO, 2010 EAU, 2014 NCCN, 2014 Recommended Grade A Category 2A in ct1a cases with major comorbidities and increased surgical risk Optional Investigational Patients with small tumours and/or significant comorbidity who are unfit for surgery should be considered for an ablative approach AT can be considered for patients with ct1a renal lesions and who are not surgical candidates in healthy patients with ct1a tumor In all cases

9 Oncological aim of ablative technology Ablative technology must be able to completly destroy all viable tissue, with no area of viable tissue left The surgeon must be able to monitor and precisely target the area to be ablated to assure complete tumour destrucion Low morbidity

10 Autorino R et al. Urol Oncol 2012; 30:

11 Mechanisms of Cryoablation Renal tumour (- 40 C) Normal renal tissue ( C)

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

13 Laparoscopic Cryoablation (LCA) Transperitoneal - anterior renal mass Retroperitoneal - posterior renal mass

14 Percutaneous Cryoablation (PCA) MRI guided CT guided

15 Cryoablation approaches

16 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

17 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)

18 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

19 Radiofrequency Ablation (RFA): Percutaneous Approach

20 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: Aron M, Gill IS. Eur Urol 2007; 51:

21 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:

22 Cryoablation: meta-analysis of case series studies (efficacy 89%) Successfully treated tumour was defined as no growth or no evidence of recurrence on CT scan or MRI El Dib C. et al. BJU Inter 2012; 110:

23 Cryoablation: meta-analysis of case series studies (complications 20%) El Dib C. et al. BJU Inter 2012; 110:

24 Cryoablation: functional outcomes Autorino R et al. Urol Oncol 2012; 30:

25 RFA: meta-analysis of case series studies (efficacy 90%) Successfully treated tumour was defined as no growth or no evidence of recurrence on CT scan or MRI El Dib C. et al. BJU Inter 2012; 110:

26 RFA: meta-analysis of case series studies (complications 19%) El Dib C. et al. BJU Inter 2012; 110:

27 RFA: survival outcomes Ma Y. et al. BJU Inter 2014; 113:

28 RFA: survival outcomes Wah TZ. et al. BJU Inter 2014; 113:

29 RFA: survival outcomes Wah TZ. et al. BJU Inter 2014; 113:

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

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

32 Alternative Treatments: Differences in clinical application Patient s age(yrs) * 66 * 67 * NSS Cryoabl RFA AS Kunkle DA et al J Urol 2008; 179: *p < 0.05

33 Alternative Treatments: Differences in clinical application 4 3,5 3 2,5 3,4 Tumour size (cm) * * 2,5 2, ,5 1 0,5 0 NSS Cryoabl RFA AS Kunkle DA et al J Urol 2008; 179: *p < 0.05

34 Alternative Treatments: Differences in clinical application Follow-up (months) 40 * * * NSS Cryoabl RFA AS Kunkle DA et al J Urol 2008; 179: *p < 0.05

35 Alternative Treatments: Pathological confirmation of SRM Kunkle DA et al J Urol 2008; 179:

36 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:

37 Indications for Ablative Therapies AUA, 2009 ESMO, 2010 EAU, 2014 NCCN, 2014 Recommended Grade A Category 2A in ct1a cases with major comorbidities and increased surgical risk Optional in healthy patients with ct1a tumor Investigational In all cases Patients with small tumours and/or significant comorbidity who are unfit for surgery should be considered for an ablative approach AT can be considered for patients with ct1a renal lesions and who are not surgical candidates