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

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80

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3 6 9 12

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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

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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

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iver

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10

20

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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

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3 6 9 12

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Years From Liver Resection or RFA

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* 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

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0

10

20

30

40

50

60

70

80

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3 6 9 12

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o

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P = 0.086

* No Neoadjuvant Therapyo Neoadjuvant Therapy

Years From Liver Resection or RFA

Perc

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P = 0.140

10

20

30

40

50

60

70

80

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3 6 9 12

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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