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AN13 METASTATIC NEOPLASMS - PRIMARY SITE "UNKNOWN"

Document
Last amended 
1 July 2015

Advisory from Disability Compensation Branch

No13 of 2000

 

This is an advisory note only.  It was prepared by Medical Officers of the Department of Veterans' Affairs , Disability Compensation Branch and Legal Services Group.  All have agreed this policy view.  It is not a Repatriation Commission Guideline or a Departmental Instruction.   The advice is not intended to conflict with the proper application of the Veterans' Entitlements Act 1986 or the judgements of the Courts.  It may be subject to change as a result of further interpretation by the Courts of the legislation.  Nevertheless it represents a considered view that should be taken into account by all delegates.

 

METASTATIC NEOPLASMS - PRIMARY SITE "UNKNOWN"

 

Purpose

The purpose of this advisory is to provide guidance on what to do when a claim is received for a cancer, and the primary site of that cancer is unknown.

This advisory replaces Departmental Instruction B41/95 of 18 July 1995 and takes account of recent Federal Court decisions concerning the steps to take in deciding a claim (Deledio) and the standard of proof to be applied to the diagnosis of an injury, illness or disease (Cooke, Gosewinkel)

 

Background

All malignant neoplasms originating at a particular site in the body (the primary site) are capable of spreading to other parts of the body.  Neoplasms at a distant site that have spread from the primary site are known as metastases (or secondaries).  In some patients the first evidence of a cancer may be from the metastases and the primary site may not be known.

Cases where metastatic disease is present but the primary site is unknown account for approximately 5% of all solid cancers. 

  • The primary tumour is too small to detect.
  • The primary tumour has regressed.
  • Sufficient investigation to identify the primary site has not been undertaken.

When the primary site is unknown after an initial diagnosis, in a large proportion of cases it will remain unknown even after thorough investigation.

 

Standard of Proof

The standard of proof that applies when confirming the diagnosis of a disease, illness or injury is “reasonable satisfaction”, that is “more probable than not”.

If the primary site of a cancer is uncertain, then in order for a particular primary site to be confirmed as the diagnosis, the material before the decision maker must indicate that it is probable or more likely than not that the cancer arose at that site.

Protocols for dealing with cases

Step 1(a)

For living veterans, the decision maker should first consider whether the veteran has undergone an adequate diagnostic process.  This should generally comprise:

  • Careful history.
  • Thorough physical examination.
  • An attempt to obtain histological or cytological confirmation and identification of the tumour type.
  • Pathology tests: Full blood count; liver and renal function tests; urinalysis; stool examination for occult blood.
  • Radiology tests: Chest X-ray; CT scan of the abdomen and pelvis.

If such a process has not occurred, the decision maker should take account of the circumstances of the individual case and then, in consultation with a medical adviser, decide what investigation should be arranged.

Investigations additional to the above, particularly invasive tests such as endoscopies, are only warranted where there is a good clinical indication (e.g. relevant symptoms or abnormality on physical examination).  Such further tests have a low detection rate and are unlikely to change the treatment or prognosis.1

Step 1(b)

For deceased veterans, autopsy results should be obtained if available.  In a significant proportion of cases, the primary site will remain unknown despite an autopsy.

Step 2

Evaluate the evidence by considering:

  • The histology and the site or sites of the metastatic disease (taking account of the scientific information below).
  • The presence of any symptoms or signs suggestive of primary cancer at a particular site.
  • The results of relevant investigations, both positive and negative.
  • The veteran's past history of disease, treatment and carcinogenic exposures.

Step 3

Discuss the evidence with a medical adviser and then consider the need for further evidence or specialist opinion.

Step 4

If possible, determine the probable primary site.  If this can be done then the primary cancer and the metastases should be regarded as one disease and the RMA SOP for the primary site should be applied to the claim.  The diagnostic label should include a reference to the metastatic disease.  If a probable primary site can be determined and a SOP applied, then the decision maker should proceed to determine the application and apply the four steps of the decision making as outlined in the Commission guidelines relating to the Deledio Full Federal Court decision.

 

If a probable primary site cannot be determined:

For reasonable hypothesis cases:

If no primary site can be determined then the disease or cause of death becomes cancer of unknown primary site (or similar), which is a non-SOP condition.  Any hypothesis regarding the connection to service has to be considered in accordance with the pre SOP law relying on the cases of East / Bushell / Bey.

This means, for example, that if a veteran has metastatic adenocarcinoma, the likely primary site for which cannot be determined, the hypothesis raised may be that the veteran's cancer arose due to a heavy service-related smoking habit (on the basis that most of the more common possible primary sites for adenocarcinoma are smoking-related).  This hypothesis could not satisfy the requirements of the case law.  As was said in East, “a reasonable hypothesis requires more than a possibility, not fanciful or unreal, consistent with the known facts.  It is a hypothesis pointed to by the facts, even though not proved on the balance of probabilities.”

In the circumstances described the hypothesis relates to material that raises a mere possibility which is not enough to satisfy the requirements of the law. point to

 

For balance of probabilities cases:

If the decision maker cannot be reasonably satisfied about the diagnosis, then the case is a non-SOP claim for cancer of unknown primary site (or similar). The approach outlined for reasonable hypothesis matters should then be followed.  In the circumstances it would be an attempt to say that while I cannot be reasonably satisfied that the primary site was “the liver”, nevertheless I am reasonable satisfied that the unknown primary site was “the liver”.  This would be a contradiction.

Note: There is no RMA SOP that applies to the category of 'cancer of unknown primary site'.  An RMA SOP for cancer of a particular site does not apply if the cancer at that site has metastasised from another site.  This is a medical issue not a legal one and the absence of a metastases in a SoP for a particular cancer site or type does not allow any unfavourable conclusion to be made about relation to service.

 

General epidemiology and pathology of metastatic cancer

The following general information from the scientific literature should be of some assistance when trying to determine a likely primary site.

 
Histology of metastatic disease

In general, most metastatic tumours in adults are carcinomas.  In cases of metastases of unknown primary site, approximately half are adenocarcinomas.  Poorly differentiated/undifferentiated and squamous cell carcinomas account for approximately 30%, with lymphomas, sarcomas, melanomas, germ cell tumours, neuroendocrine tumours and other types being uncommon.

A given type of carcinoma can arise at many sites in the body (e.g. adenocarcinoma may arise in the lung, prostate, colon, rectum, stomach, pancreas, kidney and many other sites), so the identification of a particular histological type does not establish the primary site.  Certain morphological (cell) features are frequently associated with specific sites (e.g. clear cells in the case of kidney cancer), but these are also not diagnostically specific.  Histology may suggest a particular primary site or a short-list of possible sites, but it will not definitively establish the origin of metastatic carcinoma.

For some non-carcinomas, histopathology of metastases will positively identify the type of primary disease and allow confirmation of diagnosis.  Using advanced immunocytochemical techniques, pathologists can establish with certainty a diagnosis of lymphoma, sarcoma, melanoma, germ cell tumours and neuroendocrine tumours. Such information will be sufficient to confirm relevant diagnoses, particularly Non-Hodgkin's Lymphoma, Soft Tissue Sarcoma and Malignant Melanoma of the Skin.

In cases of metastases of unknown primary site where the primary is subsequently able to be detected (e.g. at autopsy), the most frequently seen primary sites are lung, pancreas, colon/rectum, stomach, liver and kidney.  None of these sites accounts for more than 10% of total cases.  Some commonly occurring tumours are relatively easy to detect and therefore infrequently present as a cancer of unknown primary site (e.g. prostate, breast).

 

Site of metastatic disease

For known primary cancers, particular patterns of metastatic spread are commonly seen.  For example, lung cancer and prostate cancer often spread to bone, and colon cancer typically spreads to the liver.  Therefore, metastases at certain sites are seen more frequently with particular primary cancers.  However, many cancers can spread to the common metastatic sites (i.e. lymph nodes, liver, bone, lung, brain).  Thus, the presence of metastases at a particular site does not often provide a firm clue to the site of an unknown primary.  Nevertheless, the metastatic site, in conjunction with other available evidence, may suggest a likely primary site.  The following table provides general data (not specific to the veteran population) on the common metastatic and primary sites:

 

Site of metastases

Common primary site

Approximate likelihood

Brain

Lung

Gastrointestinal tract

Melanoma

Lymphoma

70%

9%

2%

2%

Bone

Lung

Prostate

40%

17%

Cervical lymph nodes

Mouth

Pharynx

Larynx

Skin

Lung

Thyroid

 50%

 50%

 50%

<10%

<10%

<5%

Liver

Lung

Colon/Rectum

Pancreas

Liver

Melanoma

Breast

Stomach

18%

17%

16%

9%

6%

6%

5%

Lung

Lung

Colon/Rectum

Breast

Kidney

Prostate

Thyroid

NA

NA

NA

NA

NA

NA

Malignant pleural effusion

Breast

Lung

Lymphoma

24%

19%

10%

Malignant ascites

Colon/rectum

Stomach

NA

NA

 

NA = not available.

 

Note:This does not mean that it is not possible or even probable.  Fore the purpose of  an “ hypothesis” they should be considered and the normal Deledio approach adopted.

 

This paper is prepared with the assistance of the Decision Support Unit

 

Dr Jon Kelley

Dr Bev Grehan

 

 

 

 

John Douglas

Director

Policy Eligibility and Research

 

8 December 2000