Joint Hospital Joint Hospital Surgical Grand Surgical Grand

RoundRound2121stst July, 2012 July, 2012

RHRH

Liver Secondaries Liver Secondaries with Occult Primary with Occult Primary

How far should we go?How far should we go?

Dr Chan Man Pan Dr Chan Man Pan Caritas Medical CentreCaritas Medical Centre

TerminologyTerminologyDifferent terms has been used by Different terms has been used by

investigatorsinvestigatorsUnknown or occult primary tumor, Unknown or occult primary tumor,

Metastasis of unknown origin, Tumor of Metastasis of unknown origin, Tumor of unidentified originunidentified origin……..

Currently, the most widely accepted Currently, the most widely accepted term is term is ““Cancer of Unknown PrimaryCancer of Unknown Primary”” (CUP)(CUP)

DefinitionDefinition

Pavlidis, N., et. al. (2003). Diagnostic and therapeutic management of cancer of an unknown primary. European Journal of Cancer, 39(14), 1990-2005.

Magnitude of problemMagnitude of problem

Pavlidis, N., et. al. (2003). Diagnostic and therapeutic management of cancer of an unknown primary. European Journal of Cancer, 39(14), 1990-2005.

EpidemiologyEpidemiologyAnnual age-adjusted incidence is 7 Annual age-adjusted incidence is 7 –– 12 12

cases per 100,000 population / year in USAcases per 100,000 population / year in USAMedian age at presentation ~ 60 years oldMedian age at presentation ~ 60 years oldSlightly male predominant Slightly male predominant No obvious aetiological or risk factor can be No obvious aetiological or risk factor can be

identifiedidentifiedCommonly presented as lymph node or Commonly presented as lymph node or

liver metastasis liver metastasis

Pavlidis, N. et. al. (2009). Carcinoma of unknown primary (CUP). Critical reviews in oncology/hematology, 69(3), 271-8.

Lazaridis, G., et. al (2008). Liver metastases from cancer of unknown primary (CUPL): a retrospective analysis of presentation, management and prognosis in 49 patients and systematic review of the literature. Cancer treatment reviews, 34(8), 693-700.

Liver secondaries with Liver secondaries with occult primaryoccult primary

Aggressive and resistant disease Aggressive and resistant disease with a grim outcomewith a grim outcome…………

How far should we go in How far should we go in investigating?investigating?

Does surgery have a role?Does surgery have a role?

How far should we go?How far should we go?Searching for primary is meaningful Searching for primary is meaningful

only if management can be affected only if management can be affected Chance of successfully locating the Chance of successfully locating the

primary?primary?

Armamentarium Armamentarium History taking & physical examHistory taking & physical examBasic blood test, Urinalaysis, Fecal Basic blood test, Urinalaysis, Fecal

occult bloodoccult bloodSerum tumor markers Serum tumor markers Imaging (CXR CT PET MRI Imaging (CXR CT PET MRI

Mammography)Mammography)EndoscopyEndoscopyHistologyHistology

Tumour marker Tumour marker

Pavlidis, N., et. al.(2003). Diagnostic and therapeutic management of cancer of an unknown primary. European Journal of Cancer, 39(14), 1990-2005.

Non specific elevation of multiple markers in majority of CUP patient

Tumour markerTumour markerRoutine measurement of epithelial tumour Routine measurement of epithelial tumour

markers is not recommended markers is not recommended However, in some cases, it might be However, in some cases, it might be

diagnostically helpful—eg, beta-HCG and AFP diagnostically helpful—eg, beta-HCG and AFP are increased in patients with poorly are increased in patients with poorly di erentiated carcinoma of midline distribution, ffdi erentiated carcinoma of midline distribution, ffas are PSA in men with bone metastasesas are PSA in men with bone metastases

CA-125 in women with primary serous CA-125 in women with primary serous peritoneal adenocarcinoma, and CA15-3 in peritoneal adenocarcinoma, and CA15-3 in women with isolated axillary adenocarcinoma.women with isolated axillary adenocarcinoma.Pavlidis N, et. al. (2012). Cancer of Unknown Primary site. Lancet. 14;379(9824):1428-35

PET CTPET CT

Kwee, Thomas C.et. al. (2009). Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. European Radiology. 19(3):731-744.

PET CTPET CT

Kwee, Thomas C.et. al. (2009). Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. European Radiology. 19(3):731-744.

PET CTPET CT

Kwee, Thomas C.et. al. (2009). Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. European Radiology. 19(3):731-744.

PET CTPET CT

Kwee, Thomas C.et. al. (2009). Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. European Radiology. 19(3):731-744.

PET scan VS PET CTPET scan VS PET CT

Gutzeit, A. et al. (2005). Unknown primary tumors: detection with dual-modality PET/CT--initial experience. Radiology, 234(1), 227-34.

Whole body MRIWhole body MRINo published data on this topicNo published data on this topic

Diagnostic EndosocpyDiagnostic EndosocpyPanendoscopy, OGD, Colonoscopy, Panendoscopy, OGD, Colonoscopy,

bronchoscopybronchoscopyGuided by Clinical and Laboratory findingGuided by Clinical and Laboratory finding

GI endoscopy in patients with abdominal symptoms GI endoscopy in patients with abdominal symptoms or fecal occult blood + ve, or histology point to a GI or fecal occult blood + ve, or histology point to a GI tract origintract origin

Pavlidis, N. et. al. (2009). Carcinoma of unknown primary (CUP). Pavlidis, N. et. al. (2009). Carcinoma of unknown primary (CUP). Critical reviews in Critical reviews in oncology/hematologyoncology/hematology, , 6969(3), 271-8(3), 271-8..

Endoscopic studies of asymptomatic areas identify Endoscopic studies of asymptomatic areas identify the primary tumour in less than 10% of such casesthe primary tumour in less than 10% of such cases

Gaber AO, et al. (1983). Metastatic malignant disease of unknown origin. Gaber AO, et al. (1983). Metastatic malignant disease of unknown origin. Am J Surg.Am J Surg. 145:493-497 145:493-497

Pavlidis N, et. al. (2012). Cancer of Unknown Primary site. Lancet. 14;379(9824):1428-35

In searching for primaryIn searching for primaryPrimary tumor can only be located in Primary tumor can only be located in

20% to 30% of case (with 20% to 30% of case (with combination of imaging, endoscopy combination of imaging, endoscopy and histology)and histology)

Most common primary site is lung, Most common primary site is lung, colorectal and pancreascolorectal and pancreas

Pavlidis, N., et. al. (2010). Cancer of unknown primary site: 20 questions to be answered. Annals of oncology: official journal of the European Society for Medical Oncology / ESMO, 21 Suppl 7(Supplement 7), vii303-7

Prognostic factorsPrognostic factors

Lazaridis, G., et. al (2008). Liver metastases from cancer of unknown primary (CUPL): a retrospective analysis of presentation, management and prognosis in 49 patients and systematic review of the literature. Cancer treatment reviews, 34(8), 693-700.

Prognostic factorsPrognostic factors

Prognostic factor Prognostic factor Certain histological subgroup are Certain histological subgroup are

more amenable to treatment more amenable to treatment Liver biopsy is essential as a primary Liver biopsy is essential as a primary

diagnostic procedure.diagnostic procedure.

Neuroendocrine carcinoma Neuroendocrine carcinoma with liver metastasiswith liver metastasis

Pancreas, right hemicolon and small Pancreas, right hemicolon and small intestine are most frequent primary intestine are most frequent primary site site

Surgical resection in curative intent Surgical resection in curative intent can offer survival benefit in selected can offer survival benefit in selected casescases

5 year survival rate 60-80% 5 year survival rate 60-80%

Pavel, M., et al. (2012). ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology, 95(2), 157-76.

The American surgeon; Jun 2004

Median follow up 9 monthsMedian Disease free survival 6.5 months

SummarySummaryHow far should we go in How far should we go in

investigating?investigating?

Hawksworth et al, (2004) Surgical and Ablative Treatment for Metastatic Adenocarcinoma to the liver from Unknown Primary tumor. The American surgeon, 70(6), 512 - 517

PET/PET-CT

SummarySummaryHow far should we go in managementHow far should we go in management

A multidisciplinary approachA multidisciplinary approachMore studies are neededMore studies are needed

Thank youThank you