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Explaining CUP

Cancer of Unknown Primary (CUP) is hidden cancer. The term is applied when a patient is diagnosed as having cancer which has spread (metastatic cancer), but the origin of the cancer cannot be identified (through imaging or pathology). This makes treatment, which is based on the profile of the primary cancer, extremely difficult.

Initial clinical presentations are usually non specific and the patient may have cancer that has spread to more than one part of the body. The origin of the cancer can sometimes be found through investigations; and sometimes it remains hidden. Finding the primary site, or the tissue of origin, is important for treatment. If a secondary cancer appears in the lungs, for example, but originated in the bowel, it remains bowel cancer genetically and needs to be treated as such.

CUP probably accounts for 2-3% of cancer diagnoses; but this figure depends on how CUP is defined. Other terms for CUP include: Tumour of Unknown Origin, Occult Primary Malignancy – Occult meaning hidden from the Latin Occultus – and, more specifically, Carcinoma of Unknown Primary. Depending on their features, cancers are classified as either carcinoma, sarcoma, lymphoma or melanoma. Most CUP definitions are of metastatic carcinoma of unknown primary. But further definitions are needed to achieve effective treatment.

The pathology samples of blood, and tissue from a biopsy if one is taken, give the doctors clues but the reason CUP is so problematic is because in these patients the cells have lost their unique features in the cancer spread. This makes identifying the original cancer cells (the target of systemic treatment e.g. by chemotherapy) difficult.

Because carcinoma of unknown primary may originate in any epithelial cells in the body, and CUP biology is not understood (other than that the primary stays small or disappears yet spreads unpredictably) it is a challenging diagnosis for the cancer doctor as well as the patient.

CUP is a very complex condition which takes many different forms so the cancer is likely to be very different for every patient, with widely different outcomes.  Improving genetic, pathological and radiological techniques will reduce the incidence of CUP in the future.

Please note: We do not offer medical advice. If you have any medical queries you should direct them at a qualified medical practitioner. We offer information which is intended to help patients – their carers, families and friends – and those who want to know more about the CUP phenomenon.

Why is the primary hidden?

‘What, Why and How’ are fairly typical reactions to a CUP diagnosis. It seems incomprehensible in our scientific age that a Primary is invisible. There are a number of possibilities for the invisibility including:

  • Size of a grain of rice or smaller. The primary may be very small – too small to be picked-up by present day tests including ultrasound, CT scans, MRI and PET.
  • Fallen on stony ground. The primary may have been successfully attacked by the body’s immune system as it tries to get a toehold and has migrated through the body to find sanctuary in a place where it can thrive and confuse the immune system.
  • Self healing. The primary might have ‘self healed’ or been be pushed out of the body if, for example, it was hanging perilously to part of the digestive system after it has spread.
  • Hidden. The secondaries, if growing close to the primary, may make it difficult to distinguish from a larger cancer mass.

Who does CUP affect and what are the ‘routes to diagnosis’?

CUP affects men and women almost equally. It is rare, but not unknown, in children and as with all cancers the majority of people affected are over 60 years of age. About 5% of those with CUP are under 50. Statistics should always be treated with caution but the detailed data show slightly more women than men are affected. There are no particularly significant geographic differences in the distribution of CUP by regional networks in the UK that could offer any clue to the nature of CUP. (Whilst the link shows some differences this is likely to reflect different registration practices by cancer registries.)

The majority of those found to have CUP present as an emergency i.e. through Accident & Emergency.  This reflects a number of factors: 40% of those with CUP are aged 80 or over; ‘deprived’ patients are likely to present to A&E; and because CUP symptoms are non specific it is difficult to be alerted early to cancer. The data show that those presenting through A&E rather than through their GP have a poorer survival rate. Some 10% of all emergency presentations are CUP (NCIN, 2014).

CUP statistics

There is a delay  of years before the data on cancer incidence and mortality is available in the UK. A comprehensive analysis of annual cancer incidence and mortality is available from Cancer Research UK (click on the document for incidence and mortality in the 10 commonest cancers to see CUP figures). The good news is that UK CUP statistics over time show the problem of CUP is declining; but that will be of little comfort for someone facing a diagnosis now. Improving genetic, pathological and radiological techniques will probably reduce the incidence further in the future (if the disease continues to be measured in the same way).

CUP is a problem all over the world and this is shown in an analysis of international CUP occurence (included in the poster in the link). It should be noted that the reliability of the data is questionable from some countries.