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Cancer of Unknown Primary Clinic (CUP)

Over 1300 people in the Netherlands are diagnosed with cancer of unknown primary (CUP) every year. This cancer type is also known as an occult primary, metastases of unknown origin (MUO), metastatic malignancy of unknown origin, or metastatic cancer of unknown primary. These people are told that they are terminally ill as a result of metastases, but that the location of the primary tumor, the origin of the cancer, or carcinoma, cannot be determined. In most cases, this means that it is not possible to determine the best treatment option because most cancer treatments are tied to a specific tumor type. CUP patients have often already faced an uncertain, frustrating, and tedious diagnostic process, which did not lead to the identification of the primary tumor. The results and treatment remain uncertain.

Please keep in mind that it is simply not always possible to find the source of the carcinoma, not even with the most advanced diagnostic techniques. That's why CUP is seen as a separate condition. At the Netherlands Cancer Institute, we have a dedicated team of experts who specialize in care for patients with CUP. We also conduct scientific research into the benefits of whole-genome sequencing (WGS) for patients with CUP, and whether this may lead to a suitable treatment option for these patients.

Our work

What to expect at the NKI?

The NKI has a specialized CUP care team. Patients with CUP can come to the NKI for a second opinion with our CUP team. You will be seen by a medical oncologist (internist) from our CUP care team at our clinic or through a video call. This specialist will review your details - results of previous radiology diagnostics, endoscopy results (a procedure that looks at the inside of your stomach and/or esophagus), and the pathology results of any biopsies that were taken. If necessary, your medical oncologist can look at the scans again. Depending on your situation, we may want to request additional diagnostics. It is important to keep in mind that these additional diagnostics will only be available if we expect that the results of these examinations could influence or determine your treatment; your overall physical shape and fitness levels are taken into consideration as well. 

We will request all biopsies from your current hospital, so the NKI pathologists can analyze them again. If necessary, our pathologists can perform additional tests on these biological samples. IOur pathologists may ask you to come in to have another biopsy taken, but only if the CUP team believes that this could be of additional value. This will allow us to perform whole-genome sequencing (WGS), which offers the following benefits:

  • This procedure may reveal the primary tumor, which would allow us to deliver a treatment specific to that tumor type;
  • We may detect specific DNA mutations for which we have a treatment option available as part of a trial.
Serena Marchetti
The specialization of our CUP team in terms of care and research is an important step towards offering treatment for patients with cancer of unknown primary.
Serena Marchetti Internist

Our care

What kind of CUP care do we offer?

Many patients who have been diagnosed with CUP have already been through an extensive diagnostic process. This may have been physically or mentally taxing, have taken a long time, or have caused uncertainties and anxiety. This is why our CUP team works hard to make sure that any necessary additional examinations will be scheduled as soon as possible. CUP requires a broad but highly specialized approach. Our CUP care team consists of highly committed expert medical oncologists (internists) and pathologists who collaborate closely and share even the smallest points of reference that could potentially lead to the discovery of the primary tumor. Our pathology department meets every week to discuss whole genome sequencing for CUP patients.

After an elaborate analysis of all diagnostic examinations, your medical oncologist will discuss a potential treatment plan with you. In certain cases and after careful deliberation, we may decide not to start a treatment, in which case your medical oncologist will discuss options for palliative treatment with you. If treatment is an option, this will usually be delivered at the referring hospital in your area, by your medical oncologist. In certain cases, we may discuss the option to participate in a trial with you, either at the NKI or at a different center.


Do I need a referral?

If you have been diagnosed with metastatic cancer of unknown primary at a different hospital, or if your general practitioner wants to refer you to us, you can come to our institute for a second opinion. Please do not wait too long before you request your second opinion. You will need a referral from your medical oncologist/internist or general practitioner, who will submit all the results from previous examinations to us. Would you like more information about (the possibility of) a second opinion? Please see the following page, or contact our Patient Information Center at +31 (0)20-5129111.

How to set up your appointment?

Once we have received your data, we will review everything to find out whether the referral is complete, and how much urgency is required. Afterward, we will set up an appointment with you. Someone will call you to schedule a date for your appointment.

CUP care team

The CUP care team at the Netherlands Cancer Institute excels at CUP care. The CUP care team consists of all specialists below. if necessary, they can count on the support of our radiologists and nuclear health specialists. Our CUP team is experienced in palliative care and includes pain specialists as well as psychological support. Several members of our CUP care team are involved in various national initiatives concerning CUP.

News and innovation

Scientific research

The NKI is a Comprehensive Cancer Center, which means that our institute meets the highest standards for quality in research and care. We distinguish ourselves through the full integration of research and care, which is reflected in the close collaboration between the researchers and physicians on our CUP care team. Researchers are actively investigating CUP. We are a frontrunner in the Netherlands in terms of Whole Genome Sequencing (WGS), including its application for patients with CUP. In collaboration with your insurance company, this has been an important contribution to the basic coverage of WGS for CUP patients. The NKI also provides treatment as part of a trial. This is where we conduct research into new cancer drugs.


Relevant organizations and websites

You can use the following organizations to find peer support groups (mostly in Dutch):

For more relevant information, please see the following websites (in Dutch):

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