Liver Resection or Ablation for Metastatic Adrenocortical Carcinoma
R. Taylor Ripley, M.D., Clinton D. Kemp M.D., Aarti Mathur, M.D., Jeremy L. Davis, M.D., Richard E. Royal, M.D.,
Steven K. Libutti, M.D., Seth M. Steinberg, PhD., Bradford J. Wood, M.D., Udai S. Kammula M.D., Itzhak
Avital, M.D.
Surgery Branch, National Cancer Institute / NIHBethesda, MD
Introduction
• Adrenocortical carcinoma:– 0.5 – 2 cases / million.– ~ 0.2% cancer deaths in US.– Second most aggressive endocrine
cancer (anaplastic thyroid cancer first)
– Male : Female – 1 : 1.5
• Presentation:– Hormonal Excess: ~60%– Abdominal Mass: ~40%
Pommier et al. Surgery. 1992; 112: 963-71.
Liver ACC metastases
Introduction
• Prognosis:– 5-year survival about 35%.– Stage dependant survival.
Icard et al. World J Surg. 2001; 25: 891-7.
Crucitti et al. Surgery. 1996; 119: 161-70.
• Metastatic disease at presentation:– 17.8%, 21.6%, and 39%.
Shulick and Brennan. Ann Surg Oncol. 1999; 6: 719-26.
Liver ACC metastases
Introduction
• Liver most common site of presenting metastatic disease:
– 57%, 10.9%, and 64%
Bilimoria et al. Cancer. 2008(12); 113: 3130-6.
• Metastatic disease to the liver after initial curative resection the 2nd most common site.
– Liver: 15% (12/82)– Lung: 20% (16/82)
Crucitti et al. Surgery. 1996; 119: 161-70. Shulick and Brennan. Ann Surg Oncol. 1999; 6: 719-26.
Liver ACC metastases
Introduction
• Complete resection is associated with prolonged survival.
• The associated may represent less aggressive disease rather than technical factors.
• Metastatic disease seems amenable to complete resection.
Shulick and Brennan. Ann Surg Oncol. 1999; 6: 719-26.
Liver ACC metastases
Objectives
To describe the experience with liver resection and ablation for metastatic adrenocortical carcinoma
To determine the outcome and potential prognostic factors of these patients
Liver ACC metastases
Methods• Retrospective Cohort Review:
– Liver resection or ablation performed for metastatic ACC at the NCI
• Inclusion Criteria:
– Liver resection; radiofrequency ablation; pathologically confirmed ACC
• Exclusion Criteria:
– Embolization; biopsy.
Liver ACC metastases
Age at Diagnosis 40 (6 - 73)Age at Liver Procedure 45 (8 - 73)
Sex, M/F 14 / 13
Lee Staging Classification No. (%)II 4 (15%)III 11 (41%)IV 12 (44%)
Hormonal Status at Initial Presentation No. (%)Nonfunctional 10 (37%)
Functional 17 (63%)Hypercortisolism 9 (53%)
Hyperaldosteronism 3 (18%)Virilization 3 (18%)
Feminization 2 (12%)
Disease Status After Initial Operation No. (%) or Mo. (Range)No Evidence of Disease (NED) 22 (81%)
Patient Resected to NED (n = 22)Disease-Free Interval mo., median (range) 9.0 (1 mo - 21.5+ years)
DemographicsLiver ACC metastases
Demographics: Sites and Resection of Extrahepatic Disease
Stage IV Presentation (n = 12) No. (%)Resected to NED 8 (68%)
Sites Present / Resected No. (%) / No. (%)Liver 7 (58) / 4 (57)Lung 4 (33) / 1 (25)
Spleen 1 (8) / 1 (100)Pancreas 1 (8) / 1 (100)
Peritoneum 1 (8) / 1 (100)Subcutaneous 1 (8) / 1 (100)
Liver ACC metastases
Results
RFAN = 8
Liver Resection or RFA for Metastatic ACC
N = 27
ResectionN = 19
NEDN = 11
Not NEDN = 8
Overall
YesN = 13
NoN = 6
EHD Present
YesN = 10
NoN = 3
Resection
CompleteYesN = 5
NoN = 5
Liver ACC metastases
Sites of EHDNED (Y/N) Sites of EHD Resection
Spine, Diaphragm, IVC N Diaphragm
Lung - 15 nodules bilateral Y Lungs
Adrenal bed, Omentum, Pelvis N Omentum, Pelvis
Omentum, Retroperiteum, Mesentry Y Omentum, Retroperiteum, Mesentry
Lung N None
Lung, Adrenal bed N Lung
Lung N None
Lung, Portal Vein Y Lung; Portal Vein
Lung, Retroperitoneum N Retroperitoneum
Retroperitoneum, Periportal LN Y Retroperitoneum, Periportal LN
Diaphragmatic Nodules Y Diaphragmatic Nodules
Lung N None
Lung, Adrenal bed N Adrenal bed
Extrahepatic Disease At Liver ResectionLiver ACC metastases
Surgery
Operations, No. (%):
• Wedge Left and Post. Sectionectomy: 1 (5)
• Trisectionectomy: 2 (11)
• Left Lateral Sectionectomy: 3 (16)
• Wedge Resection: 3 (16)
• Segmentectomy: 3 (16)
• Right Hepatectomy: 7 (37)•
Metastases, No. (%):
• 1: 10 (53)
• 2: 3 (16)
• 3: 1 (5)
• 4: 3 (16)
• Multiple: 2 (10)
Liver ACC metastases
Surgery
Morbidity, No. (%):
• PE / DVT 5 (26)
• Intraabdominal Abscess 2 (11)
• Wound Infection 1 (5)
• ARF and IVC Thrombosis 1 (5)
• Bile Leak (Overlap with DVT) 1 (5)•
Systemic Therapy, No. (%):
• Neoadjuvant: 9 (47)
• Adjuvant: 13 (68)
Liver ACC metastases
Results
ResectionN = 19
Liver Resection or RFA for Metastatic ACC
N = 27
RFAN = 8
NEDN = 2
Not NEDN = 6
Overall
YesN = 6
NoN = 2
EHD Present
YesN = 1
NoN = 5
Ablation
CompleteYesN = 1
NoN = 0
Liver ACC metastases
Extrahepatic Disease At Liver RFA
Sites of EHDNED (Y/N) Sites of EHD Resection
Lung. Spine N None
Bilateral Lung N None
Lung, RP, Adrenal bed N None
Lung N None
Lung, Scapula N None
Adrenal Bed Y Adrenal Bed
Liver ACC metastases
Radiofrequency Ablation
Systemic Therapy, No. (%):
• Neoadjuvant: 5 (63)
• Adjuvant: 7 (88)
Metastases, No. (%):
• 1: 2 (25)
• 2: 3 (38)
• 4: 1 (13)
• Multiple: 2 (25)
Liver ACC metastases
• Median Overall Survival:– 1.9 years
• Actuarial 5-year Survival:– 29%
• Median Potential F/u:– 6.2 yrs
N = 27Years
Perc
enta
ge S
urvi
val
0
10
20
30
40
50
60
70
80
90
100
3 6 9 12
**
**
**
****
*
*
*
*
*
*
Results: Survival after Liver Resection or Ablation
Liver ACC metastases
• Median Overall Survival:– Resection: 1.9 years– RFA: Not Reached
• Actuarial Survivals:– Resection:
• 2-yr: 50%• 5-yr: 29%
– RFA: • 2-yr: 53%
Years
Perc
enta
ge S
urvi
val
0
10
20
30
40
50
60
70
80
90
100
3 6 9 12
*
*
*
o
o
o
o
o
o
o
o
o
o
o
o
o
Results: Survival after Liver Resection or Ablation
Liver ACC metastases
• 18/19 NED liver after resection.
• Median RFS in Liver: 11 mo.
• 5-yr RFS Liver: 20%
• Median Potential F/u: 6.2 yrs.
Results: Recurrences after Resection
Years From Liver Resection
Perc
enta
ge W
ithou
t Rec
urre
nce
in th
e L
iver
0
10
20
30
40
50
60
70
80
90
100
3 6 9 12
*
*
*
*
*
*
*
*
*
*Perc
enta
ge W
ithou
t Rec
urre
nce
Years From Liver Resection
Liver ACC metastases
• Median OS All Patients:– DFI < 9 mo: 0.9 yrs– DFI > 9 mo: 4.1 yrs– P = 0.013
• Median OS Resection:– DFI < 9 mo: 1 yr– DFI > 9 mo: 3 yrs– P = 0.047
0
10
20
30
40
50
60
70
80
90
100
3 6 9 12
*
*
*
*
*
*
*
*
o
o
o
o
o
o
Years From Liver Resection or RFA
Perc
enta
ge S
urvi
val
* DFI < 9 monthso DFI > 9 months
Results: DFI after Adrenalectomy is Associated with Longer Survival after Liver Resection
Liver ACC metastases
o*
Results: Neoadjuvant Therapy Prior to Liver Procedure Is Not Associated with Prolonged Survival
Years From Liver Resection
Perc
enta
ge S
urvi
val
0
10
20
30
40
50
60
70
80
90
100
3 6 9 12
*
*
*
*
*
o
o
o
o
o
o
o
o
P = 0.086
* No Neoadjuvant Therapyo Neoadjuvant Therapy
Years From Liver Resection or RFA
Perc
enta
ge S
urvi
val
P = 0.140
10
20
30
40
50
60
70
80
90
100
3 6 9 12
*
*
*
*
*
*
o
o
o
o
o
o
o
o
o
o
Liver ACC metastases
Conclusions
• This study represents a highly selected group of patients, therefore the conclusion should be evaluated with caution.
• Despite resection of metastatic liver lesions, most patients experience recurrences both in the liver and systemically.
• Long-term hepatic disease control can be obtained in some patients.
• Patients with longer DFI after initial adrenalectomy may be more appropriate candidates for liver resection.
• The value of liver resection for metastatic ACC remains controversial.
Liver ACC metastases