The Invisible NET Patient Population 

Exaggeration or close to the truth?


I found some of the quotes from the recent NET SEER Database study (Dasari et al) very interesting.  The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program is a comprehensive source of population-based information initiated in 1973 that is updated annually. Although the study is US-based, it represents the largest study of Neuroendocrine Neoplasms (NENs) ever recorded and is therefore a good guide to what might be found beyond USA. In fact, other national declarations of incidence and prevalence of NENs seem to bear these statistics out, i.e incidence rates of 7-8/100,000 …… almost 7 times the rate recorded in the 1970s. If you want to understand the factors behind this massive increase, I covered this extensively in my post “Neuroendocrine Neoplasms – not as rare as you think“.  In this article, I looked at USA and beyond. Those who are regular readers of my articles will already know I’ve been ‘banging on’ about this for a few years. Other organisations and individuals (including NET specialists) are now indicating these tumors are not rare, some vindication for my aforementioned ‘banging on’.  This is now a serious disease with some serious statistics behind it and we need a new way of doing things.

There are two further quotes which I’d like to focus on in this article:

1. From the NET SEER Database study published 2017:

…… many cases of NETs may not have been reported to cancer registries unless considered malignant…… it is likely that we have underestimated their true incidence and prevalence” – i.e. the slide here:

SEER 2012 Underestimated

2. From Dana Farber (Kulke, Chan):

“Estimated more than 200,000 undiagnosed cases in the US” – this slide here:


…. But what do these quotes actually mean?  See below

Underestimating the true incidence and prevalence of NENs

I studied the latest SEER NET study, formally titled “Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States” (authored by Arvind Dasari, MD, MS; Chan Shen, PhD; Daniel Halperin, MD; et al). From this document, I can see the authors were aware of the well-known faults in cancer registries worldwide and the effect this has on the true incidence and prevalence of Neuroendocrine Cancer.  These issues, which are a worldwide problem, include the incorrect registration of Neuroendocrine Cancer as other types based on the anatomical location of the primary tumor.  At this point, you may wish to check out my post “The Human Anatomy of Neuroendocrine Cancer” which provides some real-life examples of the confusion between primary Neuroendocrine location and other cancers. That said, things are definitely improving because the latest SEER data shows a marked increase in the incidence of High-Grade Neuroendocrine Carcinomas (NEC), an area where this issue is prevalent. A similar increase in NEC was also illustrated in the UK’s figures from Public Health England (PHE) in 2016 (click here) indicating that cancer registries are getting better and not before time, although it has to be said this only came about due to a major intervention by NET Patient Foundation and others. Through this work, it’s becoming clear that the incidence of all NETs in UK is around 8 to 9 per 100.000 (rare threshold <=5).

But there’s another issue impacting whether a diagnosis is actually entered on a cancer registry or not.  Unfortunately, there are members of the medical community who still see well differentiated NETs as benign tumors, ‘not a proper cancer’ and still use ancient terminology ………  ‘Carcinoid’.  The WHO 2010 classification for NETs was based on the concept that all NETs have malignant potential. Here’s a quote from the UKINETS Guidelines in 2011 (Ramage, Caplin, Meyer, Grossman, et al).

Tumours should be classified according to the WHO 2010 classification (Bosman FT, Carneiro F, Hruban RH, et al. WHO Classification of Tumours of the Digestive System. Lyon: IARC, 2010). This classification is fundamentally different from the WHO 2000 classification scheme, as it no longer combines stage related information with the two-tiered system of well and poorly differentiated NETs. The WHO 2010 classification is based on the concept that all NETs have malignant potential, and has therefore abandoned the division into benign and malignant NETs and tumours of uncertain malignant potential.

The guidance in WHO 2017 for Endocrine Organs and WHO 2019 for the Digestive System reinforces this statement.

The undiagnosed NET patient population

From above, you can see why the incidence (and therefore the prevalence) of our disease has almost definitely been underestimated.  You can ignore the “in excess of 100,000”, it is most definitely in excess of 200,000 but doctors feel they cannot come out and say that becsue of the orphan drug limit of 200,000 ……politics. However, that’s not the end of my story……..

A number of statements are clear about Neuroendocrine Tumors:

  • Low/Intermediate grade well differentiated tumors are known to have been growing slowly over a number of years before discovery or accurate diagnosis occurs,
  • They can be difficult to diagnose,
  • They are not that well-known amongst the general medical population,
  • Many people are initially misdiagnosed with another condition, with some this will result in late presentation with metastatic disease.
  • Some people will be labelled with the wrong cancer as doctors often based their findings on where in the anatomy things are found (i.e. the Steve Jobs confusion)
  • Many NETs are found during autopsies.

The living undiagnosed NET patient population

It’s worth pointing out that one of the conclusions made by the recent SEER NET study is that the increase in incidence and prevalence can be attributed to a number of factors including earlier diagnosis.  This is of course excellent news.  Also, worth noting that another conclusion of the study is that we are all living longer, reflecting improvements in therapies.  This is also great news and is a factor in increased prevalence figures. However, it seems obvious that there are hundreds of thousands of people out there still be diagnosed who have tumors silently growing inside them and who are in a loop of referrals between primary and secondary care awaiting a proper diagnosis. See the Dana Farber slide above.  Please help these people by sharing this article – you never know who it will reach – Diagnosing the Undiagnosed. There’s also the problem of NETs being dismissed as benign and not recorded in cancer registries or labelled as the anatomical location cancer name in which they were found – a classic example here from Rectal NETs where a recent study published in Dec 2020 indicates that these NET types may be vastly understated having been included in the databases for Colorectal Cancer and hidden from NET figures. They are clearly more common than many of us think.  Read more here. How many other NET types have been recorded in this way?

The potential for even more undiagnosed. To add to the underdiagnoses of NETs issue, is this most amazing piece of research published in 2018 – Pan-cancer molecular classes transcending tumor lineage across 32 cancer types, multiple data platforms, and over 10,000 cases.  It was published in the American Association of Cancer Research (AACR) journal ‘Clinical Cancer Research and authored by Chad Creighton et al. D.  This was a pan-cancer piece of research which indicated that Neuroendocrine disease may be more prevalent than anyone has ever thought.  There’s a summary article here which I suggest you read fully.  The rather explosive extract is as follows:

We expected that about 1 percent of

The dead undiagnosed NET patient population

The true incidence of NETs may be much higher owing to the lack of diagnosis until after death.  For example:

  • In USA, a respected NET specialist stated that the autopsy find for (excuse the outdated terminology…….) ‘carcinoid‘ is 4 times the recorded diagnosis rate (based on the known incidence rate at the time, this is 8 per 100,000).
  • In Australia, one study claimed that 0.05% of all autopsies found a Pheochromocytoma or Paraganglioma. “
  • The Mayo Clinic experience shows that in up to 50% of cases of pheochromocytoma, the correct diagnosis is made at autopsy (ergo the incidence rate could be double what is published).
  • A Hong Kong study indicated that 1% of all autopsies discovered an ‘Islet Cell’ tumour (i.e. a Pancreatic NET or pNET).
  • In one series, (excuse the outdated terminology…….) ‘carcinoid’ tumors were found in 1.22% of 16,294 autopsies in Malmö, Sweden, 90% of which were incidental findings.

It’s possible that many of these people showed no NET symptoms during their life but …… it’s equally possible that many of these people had NET symptoms but just put up with it and/or had been diagnosed with something else, and then died without a correct diagnosis.  There is no evidence that any investigation follow ups were done so this possibility remains.

And to complete the article, a real example of where this can happen. An article claiming that former US President Dwight D Eisenhower had a biopsy confirming he had a Pheochromocytoma.  Click here.

Are you undiagnosed but suspect NETs?

You may be one of the invisible NET Patient population. Check out how you might be able to confirm or allay those fears by clicking here.


I suspect there’s an invisible patient population for many conditions but the slow-growing and relatively quiet nature of Neuroendocrine Cancer means there could be a significant undiagnosed burden walking around, looking for a diagnosis, putting up with symptoms and being treated for other conditions. I see people on forums looking for clues, social media can sometimes be helpful here. That said, I do get the feeling some do not have NETs, regardless of the symptoms they associate with the disease, but I guess many of them will go on to be formally diagnosed with something. I’m contacted by many ‘undiagnosed’ people on my own blog and supporting Facebook sites (mostly privately) and I can tell you that’s a tough gig.  I only hope I’ve given them some useful ideas about where to look or what to ask/suggest.

I feel earlier diagnosis reported in the SEER study is partly due to increased awareness, particularly in the medical world. I would also suggest that it has improved in the general population due to the explosion of social media information dissemination. It’s also accurate to say that improvements in diagnostic capabilities is also playing its part in pushing up incidence rates, just as improved therapies have pushed up prevalence rates, something emphasised by Dasari (et al) in the most recent study.  Things are improving but there is so much more to do.

The issues caused by inefficient registries together with ‘the undiagnosed’, combine to suggest there is a large invisible NET patient population out there ……. we just need to find them!  

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16 thoughts on “The Invisible NET Patient Population 

  • Ron Sekula

    Would it be a good idea to get a ct scan as one would get a colonoscopy at a certain age?
    I asked my doctor that question. His reply was that it would “ raise to many questions”.

    • I also believe there wouldn’t be enough scans and resources in existence to meet the demand, you can see how long it’s taking to inoculate the over 50s for COVID

  • Thanks Ronny, I have read and re-read so many of your posts and am so thankful for your continued education and activism! I am one of the ‘silent’ patients with a diagnosis of Carcinoid Syndrome with Occult Tumor. It has been a frustrating, difficult journey, but I thankfully had a GP that knew enough to be suspicious and at least found the needle-in-the-haystack with persistently elevated plasma 5-HIAA even though no tumors can be found on imaging.

    • My guess is it’s hiding somewhere in the folds of your small intestine.

      Have you had a Ga68 PET scan? Any signs of metastases because carcinoid syndrome is normally only present with liver metastases (there are one or two exceptions such as lung and cervix/ovaries)

    • Very difficult to prove given the changes in diagnostic technology, physician education and general awareness (social media explosion). I think he’s right though

  • Deanna Vickery, Mrs

    As usual a very interesting article which makes me think that the most important factor to finding these invisible patients is intensive training for the first-contact points ie our GPs.
    Thankyou Ronny.

    • Thanks Deanna. I’m personally not so sure that GP’s should be the main target of awareness. It is more likely that a patient will be actually diagnosed at secondary care and so gastroenterologists, oncologists, and even pathologists should be a target. Many people are referred to secondary care for “something” based on the presentational symptoms and the action of secondary care is critical. Many people are sent back to primary care from secondary care nothing found. The problem for GPs is that NETs is one of 200 cancers and one of 10,000 conditions and it’s impossible for GPs to be given “intensive training” in every single one of them. Their gut instinct, hopefully honed by 10 years of training, normally works for most. That’s not to say we should not include them in our awareness activities but the ‘NETs primer’ we send them is there alongside the ‘a’ disease primer, the ‘b’ disease primer, the ‘c’ disease primer and so on. Most of these primers will unfortunately and understandably become ‘shelfware’. Just my opinion though.

  • Jeff Drifmeyer

    ‘a large invisible NET patient population out there ……. we just need to find them’
    thanks for pointing this out. But, begs the question…what can be done about it? i.e. How do we, in fact, “find them?”
    Any thought of mounting a case finding campaign? Excellent care is available its just hard then it should be to get to, as you point out.
    ..perhaps in coordination with world NET day in Nov?
    without such a concerted effort, lives among the estimated 200K will be lost due to misdiagnosis, and inappropriate treatment. We can do better
    Jeff D

    • Well we are finding them, as you will have read, the increase in incidence is a direct result of earlier diagnosos. Ergo, the figure some years ago was very probably way above 200,000. No-one can deny that my blog is not spreading awareness, so I guess I’m doing my bit. Remember, I’m just a wee Scottish patient. However, I think the community as a whole could be more effective if it dropped the ineffectual and crazy fascination with black and white striped animals. We could certainly do better than that.

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