Sorveglianza attiva e trattamenti mini-invasivi

Sorveglianza attiva e trattamenti mini-invasivi

Vincenzo FicarraDipartimento di Scienze Sperimentali

Mediche e Cliniche – Clinica di Urologia, Università degli Studi di Udine

Active SurveillanceActive Surveillance

• Active surveillance is defined as the initial Active surveillance is defined as the initial monitoring of tumour size by serial abdominal monitoring of tumour size by serial abdominal imaging (ultrasound, CT, or MRI) with delayed imaging (ultrasound, CT, or MRI) with delayed intervention reserved for those tumours that intervention reserved for those tumours that show clinical progression during follow-upshow clinical progression during follow-up

• Active surveillance is a reasonable option for Active surveillance is a reasonable option for elderly and/or comorbid patients with small elderly and/or comorbid patients with small renal masses and limited life expectancyrenal masses and limited life expectancy

Ljungberg B. et al. EAU Guidelines, 2013


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



• 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.


Smaldone MC et al. Cancer 2012; 118: 997-1006

Pooled analysis comparing patients who did not progress to metastasis and patients who demonstrated evidence of Progression at follow-up (33.5 months)


• A substantial proportion of small renal masses A substantial proportion of small renal masses remained radiographically static after an initial period remained radiographically static after an initial period of active surveillance of active surveillance

• Progression to metastases occurred in a small Progression to metastases occurred in a small percentage of patients and generally was a late event percentage of patients and generally was a late event

• Patients who have competing health risks, Patients who have competing health risks, radiographic surveillance may be an acceptable initial radiographic surveillance may be an acceptable initial approach, and delayed intervention may be reserved approach, and delayed intervention may be reserved for patients who have tumors that exhibit significant for patients who have tumors that exhibit significant linear or volumetric growth.linear or volumetric growth.

Smaldone MC et al. Cancer 2012; 118: 997-1006

Active Surveillance with follow-up Active Surveillance with follow-up longer than 5 yearslonger than 5 years

Haramis G et al. Urology 2011; 77: 787-791

• 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

Surveillance protocols Surveillance protocols

• A definite protocol for ‘active’ surveillance of SRMs A definite protocol for ‘active’ surveillance of SRMs has yet to be definedhas yet to be defined

• A suggested approach consists to alternate between A suggested approach consists to alternate between US and cross-sectional (CT or magnetic resonance) US and cross-sectional (CT or magnetic resonance) imaging (some would argue that the inconsistency in imaging (some would argue that the inconsistency in size estimates using multiple modalities is a weakness size estimates using multiple modalities is a weakness of this approach) of this approach)

• Imaging interval: every 3months for 1 year, every 6 Imaging interval: every 3months for 1 year, every 6 months for the second year, and annually thereafter.months for the second year, and annually thereafter.


AUA, 2009 ESMO, 2010 EAU, 2013 NCCN, 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 Oncological aim of ablative technologytechnology

• Ablative technology must be able to Ablative technology must be able to completly destroy all viable tissue, with completly destroy all viable tissue, with no area of viable tissue leftno area of viable tissue left

• The surgeon must be able to monitor The surgeon must be able to monitor and precisely target the area to be and precisely target the area to be ablated to assure complete tumour ablated to assure complete tumour destrucion destrucion

• Low morbidityLow morbidity

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

Mechanisms of CryoablationMechanisms of CryoablationMechanisms of CryoablationMechanisms of Cryoablation

Normal renal tissue(- 19.4 °C)

Renal tumour(- 40 °C)

Cryoablation approaches

• Laparoscopic Cryoablation Laparoscopic Cryoablation (LCA)(LCA)

- general anaesthesia mandatory- general anaesthesia mandatory

• Percutaneous Cryoablation Percutaneous Cryoablation (PCA)(PCA)

- MRI guided (reported under GA)- MRI guided (reported under GA) - CT guided (reported under sedation)- CT guided (reported under sedation)

Laparoscopic Cryoablation (LCA)Laparoscopic Cryoablation (LCA)

• TransperitonealTransperitoneal - anterior renal mass- anterior renal mass

• RetroperitonealRetroperitoneal - posterior renal mass- posterior renal mass

Percutaneous Cryoablation (PCA)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 High-frequency alternating current emitted through electrode placed within emitted through electrode placed within targeted tissuetargeted tissue

• T° > 60° C with denaturation of T° > 60° C with denaturation of proteins; melting of cell membranes, proteins; melting of cell membranes, loss of enzymatic function, destruction loss of enzymatic function, destruction of cytoplasmof cytoplasm

Radiofrequency Ablation (RFA): Approaches

• Laparoscopic Radiofrency Laparoscopic Radiofrency Ablation (LRFA)Ablation (LRFA)

- general anaesthesia mandatory- general anaesthesia mandatory

• Percutaneous Radiofrequency Percutaneous Radiofrequency Ablation (PRFA)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 - limitation in the detection of residual

tumour in the same sessiontumour in the same session

• MRI: currently the bestMRI: currently the best - allows re-treatment of residual - allows re-treatment of residual

tumour in the same sessiontumour 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: 1224-1229Aron M, Gill IS. Eur Urol 2007; 51: 348-357

Alternative Treatments: Follow-up and outcomes

Kunkle DA et al J Urol 2008; 179: 1227-1234

• 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: 510-516El Dib C. et al. BJU Inter 2012; 110: 510-516

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%)


Cryoablation: functional outcomes


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

RFA: meta-analysis of case series studies (complications 19%)


Complications after ablative therapies for small renal tumors

Atwell TD et al. J Vasc Interv Radiol 2012; 23: 48-54Atwell TD et al. J Vasc Interv Radiol 2012; 23: 48-54

Alternative Treatments: Radiofrequency or Cryoablation


Meta-Analysis of studies published between 1980 to 2006

Alternative Treatments: Differences in clinical application


60

66

67

68

56

58

60

62

64

66

68

70

NSS Cryoabl RFA AS

**

*p < 0.05

Patient’s age(Yrs) *



3,4

2,5 2,6

3

0

0,5

1

1,5

2

2,5

3

3,5

4

NSS Cryoabl RFA AS

* *

*p < 0.05

Tumour size (cm)



54

1816

33

0

10

20

30

40

50

60

NSS Cryoabl RFA AS

* *

*p < 0.05

Follow-up (months)

*

Alternative Treatments: Pathological confirmation of SRM


Local recurrence-free survival

Campbell S et al J Urol 2009; 182: 1271-79

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: 181-190Faddegon S. et al. Urol Clin North Am 2012; 39: 181-190

Cryoablation: future perspectives


Sorveglianza attiva e trattamenti mini-invasivi

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