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

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-upActive 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 expectancyActive 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

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

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

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

Active Surveillance A substantial proportion of small renal masses remained radiographically static after an initial period of active surveillanceA 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 eventProgression 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.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:

Active Surveillance with follow-up longer than 5 years Haramis G et al. Urology 2011; 77: 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

Surveillance protocols A definite protocol for ‘active’ surveillance of SRMsA definite protocol for ‘active’ surveillance of SRMs has yet to be defined 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)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.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:

AUA, 2009ESMO, 2010EAU, 2013NCCN, 2013 Recommended in cT1a cases with major comorbidities and increased surgical risk Optional in healthy patients with cT1a tumor Investigational In all cases Grade A Patients with small tumours and/or significant comorbidity who are unfit for surgery should be considered for an ablative approach Category 2A AT can be considered for patients with cT1a renal lesions and who are not surgical candidates Indications for Ablative Therapies

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

Autorino R et al. Urol Oncol 2012; 30: 20-27

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

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

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

Percutaneous Cryoablation (PCA) MRI guided CT guided

Cryoablation approaches

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

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

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

Radiofrequency Ablation (RFA): Percutaneous Approach

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:

Alternative Treatments: Follow-up and outcomes Kunkle DA et al J Urol 2008; 179: 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

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

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

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

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

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

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

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

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

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

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

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

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

Local recurrence-free survival Campbell S et al J Urol 2009; 182: 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

Ablative therapies Vs surgery Faddegon S. et al. Urol Clin North Am 2012; 39:

Cryoablation: future perspectives Autorino R et al. Urol Oncol 2012; 30: 20-27