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-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
Active Surveillance
Lane B. et al. Curr Opin Urol 2012; 22: 353-59
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 0.4–0.5 cm/year while on
active surveillance.
Lane B. et al. Curr Opin Urol 2012; 22: 353-59
Active Surveillance
Pooled analysis comparing patients who 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
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
Active Surveillance with follow-up
longer than 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
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 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
Indications for Ablative Therapies
AUA, 2009
ESMO, 2010
EAU, 2013
NCCN, 2013
• Recommended
• Grade A
• Category 2A
in cT1a cases with
major comorbidities
and increased
surgical risk
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
• Optional
• Investigational
in healthy patients
with cT1a tumor
In all cases
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
Autorino R et al. Urol Oncol 2012; 30: 20-27
Mechanisms of Cryoablation
Renal tumour
(- 40 °C)
Normal renal tissue
(- 19.4 °C)
Cryoablation approaches
• Laparoscopic Cryoablation
(LCA)
- general anaesthesia mandatory
• Percutaneous Cryoablation
(PCA)
- MRI guided (reported under GA)
- CT guided (reported under sedation)
Laparoscopic Cryoablation (LCA)
• Transperitoneal
- anterior renal mass
• Retroperitoneal
- posterior renal mass
Percutaneous Cryoablation (PCA)
MRI guided
CT guided
Cryoablation approaches
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
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)
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
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: 1224-1229
Aron M, Gill IS. Eur Urol 2007; 51: 348-357
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
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: 510-516
Cryoablation: meta-analysis of case
series studies (complications 20%)
El Dib C. et al. BJU Inter 2012; 110: 510-516
Cryoablation: functional outcomes
Autorino R et al. Urol Oncol 2012; 30: 20-27
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: 510-516
RFA: meta-analysis of case series studies
(complications 19%)
El Dib C. et al. BJU Inter 2012; 110: 510-516
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
Meta-Analysis of studies published between 1980 to 2006
Kunkle DA et al J Urol 2008; 179: 1227-1234
Alternative Treatments: Radiofrequency
or Cryoablation
Meta-Analysis of studies published between 1980 to 2006
Kunkle DA et al J Urol 2008; 179: 1227-1234
Alternative Treatments:
Differences in clinical application
70
68
Patient’s age(Yrs)
*
*
*
68
67
66
66
64
62
60
60
58
56
NSS
Cryoabl
Kunkle DA et al J Urol 2008; 179: 1227-1234
RFA
AS
*p < 0.05
Alternative Treatments:
Differences in clinical application
4
3,5
3,4
Tumour size (cm)
*
3
2,5
*
3
2,6
2,5
2
1,5
1
0,5
0
NSS
Cryoabl
Kunkle DA et al J Urol 2008; 179: 1227-1234
RFA
AS
*p < 0.05
Alternative Treatments:
Differences in clinical application
60
54
Follow-up (months)
50
*
40
33
30
*
18
20
*
16
10
0
NSS
Cryoabl
Kunkle DA et al J Urol 2008; 179: 1227-1234
RFA
AS
*p < 0.05
Alternative Treatments:
Pathological confirmation of SRM
Kunkle DA et al J Urol 2008; 179: 1227-1234
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
Ablative therapies Vs surgery
Faddegon S. et al. Urol Clin North Am 2012; 39: 181-190
Cryoablation: future perspectives
Autorino R et al. Urol Oncol 2012; 30: 20-27