What Happens If Your Primary Cancer Tumor Cannot Be Found?

A small group of patients never knows where their cancer first started.


Breast cancer.  Prostate cancer.  Colon cancer.  Patients with cancer are labelled based on the origin of their malignancies.  This categorization serves a real purpose:  one of the most important factors in determining treatment options and prognosis is the origin of the cancer, the “primary tumor” site.

But for about three out of every 100 cancer patients, the original cancer site is never found.

  That is, the patient presents with new symptoms (such as pain or bleeding or a lump) or is asymptomatic (has no symptoms) but is found on a physical exam, routine X-ray, or other study to have cancer.  What is actually diagnosed is a cancer metastasis – a tumor (or tumors) that has grown from cells that traveled from the now-unidentifiable primary cancer and invaded another site (or sites) within the body.  The metastasis is biopsied, cancer is diagnosed, and a search is triggered for the primary tumor, a comprehensive evaluation usually heavily dependent on radiologic imaging studies such as CT scans.  But the original primary malignant tumor is never found.  And given that we label all cancer patients, this unique group is said to suffer from “cancer of unknown primary origin (CUP).”

So, how is it possible to not find the original cancerous tumor?  After all, even in patients whose cancer has already metastasized to other sites (such as the liver, lungs, bone, and/or brain), the origin of the metastases, the primary tumor, is often large and virtually always identified as a mass on a mammogram, a nodule on a prostate exam, a growth found during colonoscopy.

  So how can the primary tumor disappear?  There are several possible explanations.  Some primary tumors may outgrow their blood supply and die or shrink to an undetectable size, disappearing while distant cancer metastases continue to grow.  In other patients, an unsuspected primary tumor may be surgically removed during a procedure to treat a benign condition.

  For example, the Food & Drug Administration recently discouraged the use of a minimally invasive (“laparoscopic”) surgical tool utilized in the performance of a hysterectomy (removal of the uterus) for benign tumors called fibroids.  It turns out that, unbeknownst to anyone at the time, one in 350 women undergoing hysterectomy for this non-cancerous condition harbors a uterine cancer called a sarcoma, and the use of this specific surgical instrument (a morcellator) may spread the unsuspected cancer cells, to the detriment of the patient.

But does it matter if the primary cancer is not found?  Unfortunately for CUP patients, it matters a great deal.  Again, the actual origin of an individual’s cancer has great significance in terms of treatment options and prognosis (including survival).  Thus, while many cancers originate in similar types of tissues (for example, breast, thyroid, prostate, and other cancers all develop from glandular tissues), there are significant and clinically meaningful cellular differences between the glandular tissue types (breast versus thyroid, for example).

In CUP patients, we start by categorizing the cancer cells into one of four groups based on their appearance and other cellular features:  Adenocarcinoma (glandular tissues; about 60% of CUP cases); Poorly Differentiated Carcinoma (aggressive cancer cells which do not clearly resemble any specific tissue type; about 20% to 30% of CUP cases); Squamous Carcinoma (accounting for less than 10% of CUP cases; similar to skin and cells lining certain organs); and Neuroendocrine Carcinoma (rare; cells resembling those scattered throughout the body which produce hormones).  And today, we also can put the cancer cells through a myriad of molecular tests, searching through their DNA for a genetic fingerprint more clearly suggesting their exact tissue origin.

With as much information about the cell type as possible, cancer physicians make an educated guess as to the treatment regimen most likely to impact the cancer and benefit the CUP patient.  Unfortunately, as CUP by definition presents with metastatic (spread) disease, and given that we do not know with certainty the exact origin of the CUP patient’s malignancy, the overall prognosis is very poor.  Median survival (half survive longer and half shorter) for CUP patients is less than four months; at one year following diagnosis, less than 25% of CUP patients are alive, and at five years, less than 10%.

So what should you do if you or a loved one is diagnosed with cancer, but the primary malignancy cannot be identified?  Immediately move your care to a major cancer institution (a nationally recognized cancer center or large academic facility).  CUP is a rare malignant condition requiring experience, expertise, and technology to assess and treat, and cancer institutions are filled with experience, expertise, and technology.   Such an institution will perform advanced radiologic imaging studies and molecular testing in an attempt to identify the primary tumor and administer targeted treatment.  And if the diagnosis of CUP is unchanged, cancer institutions offer the greatest likelihood of impactful treatment and specialized, compassionate care for the CUP patient and their loved ones.

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