One of my daily alerts brought up this very interesting article published in the Journal of Gastrointestinal Oncology last month (June 2015). I personally found it fascinating. Moreover, it gave me some hope that specialists are out there looking for novel treatments to help with the difficult fight against Neuroendocrine Cancer.
This is an article about something generally described as “Intra-operative Chemotherapy”, i.e. the administration of chemo during surgery. This isn’t any old article – this is written by someone who is very well-known in Neuroendocrine Cancer circles – Dr. Yi-Zarn Wang.
The general idea behind this isn’t exactly new as there’s also a procedure known as HIPEC (Hyperthermic Intraperitoneal Chemotherapy) or “chemo bath”. This is mostly used intra-operatively for people with advanced appendiceal cancers such as Pseudomyxoma Peritonei (PMP). It normally follows extreme surgery – you can read more about this in a blog I wrote at the beginning of the year entitled “The Mother of all Surgeries”.
However, this is both different and significant because it is targeted at midgut neuroendocrine tumour (NET) patients who are often diagnosed at an advanced stage with extensive mesenteric lymph node and liver metastasis. Despite extensive surgery which needs to be both aggressive and delicate, there can sometimes be small specks left behind which will not show up on any type scan, particularly in the mesentery area. It is possible these specks could eventually grow big enough to cause fresh metastasis or syndrome recurrence/worsening and then need further invasive treatment.
The treatment aims to eliminate potential tumour residuals in mesenteric lymph node dissection beds using a safe and local application of chemotherapy agent 5-fluorouracil (5-FU). The 5-FU is delivered via ‘intraoperative application’ of 5-FU saturated gelfoam strips secured into the mesenteric defect following the extensive lymphadenectomy. The term ‘Chinese dumpings’ is used to describe the 5-FU saturated gelfoam strips once they are in place in the treatment site. I understand from other research that they can also be used in liver surgery (anecdotal from a forum site).
The report concluded that those who were treated with the intra-operative 5-FU received less follow-up surgery than those who were not (the control group). However, it added that further studies were required to evaluate its effect on long-term survival.
So…. this form of intra-operative treatment is very interesting. Incidentally there is already a form of intra-operative treatment using radiotherapy (IORT) which is a similar concept but essentially still in its infancy. However, the first IORT machine of its kind in the UK was deployed in Jun 2016. I blogged about this here.
p.s. If you get time, the introduction section of this article is a very powerful explanation of the problems and challenges faced by surgeons when presented with extensive abdominal neuroendocrine disease.
EIGHT years ago. I was diagnosed with metastatic Neuroendocrine Cancer – 26th July 2010. Until I arrived at my 5th anniversary, I hadn’t thought much about how (or if) I should mark these occasions. I never thought I would dwell on such things as ‘Cancerversaries‘ but I now totally get why many patients and survivors do.
There are various types of ‘Cancerversary‘ that for some, could trigger a mix or range of emotions including gratitude, relief and fear of cancer recurrence or growth. These milestones could be the date of a cancer diagnosis, the end of a particular type of treatment (anniversary of surgery etc) or a period since no signs or symptoms of cancer were reported. Everybody will most likely handle it their own way – and that’s perfectly understandable.
The 5 year milestone was significant, mainly I suspect, because it’s a time period very frequently used in prognostic outcome statistics. When I was researching after my diagnosis, the 5 year figure for metastatic Neuroendocrine Cancer wasn’t that great, in fact it looked less favourable than more aggressive cancers. Then I gradually worked out that the prognostic figures for Neuroendocrine Cancer were very dated (like many other things) and did not take into account improved diagnostic techniques and the introduction of a plethora of new treatments, in particular somatostatin analogues. Consequently, I no longer pay any attention to prognostic statistics – I’m actually more influenced by the large number of long-term survivors I see out there.
Check out the fantastic response to my 7th year cancerversary post. Click here to be inspired.
My cancer is treatable but not curable but I will never call it terminal. Despite some issues this year so far, I’m still here and I intend to be here next year, and for many more years after that!
It’s good to be busy, it can take your mind off stuff you don’t really want to think about. That was my tactic after being diagnosed with incurable Neuroendocrine Cancer. I just kept working and working and was still sending work emails and making telephone calls on the day I was being admitted to hospital for major surgery. After all, how could they possibly function without me? Although I was banned from work after the surgery, I still dropped an email to let them know I was doing cartwheels down the hospital corridor. They expected nothing less.
I guess the image of ‘invincibility’ was important to me at that time. It was part of my personal expectations and credibility. Some 6 weeks after leaving hospital following a 9 hour open surgery, I literally crawled back to the office, weak and drawn but determined to ‘make a statement’ by dint of my physical presence. A round of applause was given and for me this was as effective as any medicine I was taking. My credibility was intact.
Treatment, tests and consultations would now be managed around work instead of the other way – after all, they couldn’t possibly function without me? This ‘charade’ went on for some time until I eventually realised they could actually function without me and the only person expecting me to be ‘in service‘ on a treatment, testing or consultation day, was me. Additionally, it became patently obvious that people would totally understand my reasons for slowing down. However, a more serious message was being received from my body which was hinting it was more delicate than I had thought. My credibility, until hitherto sacrosanct, was taking its toll and things weren’t really back to normal. I began to realise I needed a different and better ‘normal‘.
After my ‘eureka’ moment, I totally changed my lifestyle putting my health above my credibility in the ‘pecking order’. I still keep busy – that’s important. I’m now happily doing things I enjoy at my own pace and my fatigue levels are now under control. Here’s my 5 top suggestions for prioritising your time and activities to be able to live with an incurable cancer.
Reduce your stress. This is difficult with the modern life we now lead but if you can live without things that cause you stress – cease or drastically reduce their effect on you and boldness might be required to strike the right balance.
Quality sleep. If your illness has a fatigue element, a decent night’s sleep becomes more important. Get into a routine if possible.
Take time to exercise. It doesn’t need to be a marathon or a climb up Mt Everest. Even a regular short walk is enough and you can build up from there. This also helps with the sleep, fatigue and stress reduction.
Learn to say no more often. This is difficult, particularly if you are the energetic multi-tasking go-getter type but your body has a voice – listen to it.
Do more of the things you enjoy. We’re all guilty of procrastination from time to time but get more of the things you enjoy into your calendar, it supports all the other suggestions above!
I now have a new ‘normal’ and I feel healthier and more positive. I sometimes think I might be taking on too much leading to a return to the ‘old ways’. However, the big difference today is that I have no qualms about taking myself ‘out of service‘ or reducing my workload and commitments. My body tends to remind me now and then.
This is the second article in the Neuroendocrine Cancer Nutrition series. In the first article, I focused on Vitamin and Mineral deficiency risks for patients and there is a big overlap with the subject of Gastrointestinal Malabsorption. Those who remember the content will have spotted the risks pertaining to the inability to absorb particular vitamins and minerals. This comes under the general heading of Malabsorption and in Neuroendocrine Cancer patients, this can be caused or exacerbated by one or more of a number of factors relating to their condition. It’s also worth pointing out that malabsorption issues can be caused by other reasons unrelated to NETs. Additionally, malabsorption and nutrient deficiency issues can form part of the presenting symptoms which eventually lead to a diagnosis of Neuroendocrine Cancer; e.g. in my own case, I was initially diagnosed with Iron Deficiency Anemia in association with some weight loss. Even after diagnosis, these issues still need to be carefully monitored as they can manifest as part of the consequences of having cancer and cancer treatment.
Malabsorption will present via several symptoms which may be similar to other issues (i.e. they could masquerade as, or appear to worsen the effect of a NET Syndrome). These symptoms may include (but are not limited to) tiredness/fatigue/lethargy, stomach cramps, diarrhea, steatorrhea (see below), weight loss. Some of these symptoms could be a direct result of nutrient deficiencies caused by the malabsorption. Some patients (and perhaps physicians?) could mistake these for symptoms of Neuroendocrine disease including certain syndromes, perhaps leading to prescribing expensive and unnecessary drugs when a different (and cheaper) strategy might be better.
Crash Course……. We eat food, but our digestive system doesn’t absorb food, it absorbs nutrients. Food has to be broken down from things like steak and broccoli into its nutrient pieces: amino acids (from proteins), fatty acids and cholesterol (from fats), and simple sugars (from carbohydrates), as well as vitamins, minerals, and a variety of other plant and animal compounds. Digestive enzymes, primarily produced in the pancreas and small intestine (they’re also made in saliva glands and the stomach), break down our food into nutrients so that our bodies can absorb them. If we don’t have enough digestive enzymes, we can’t break down our food—which means even though we’re eating well, we aren’t absorbing all that good nutrition.
What is malabsorption?
The malabsorption associated with Neuroendocrine Cancer is most prevalent with the inability to digest fat properly which can lead to steatorrhea. Patients will recognise this in their stools. They may be floating, foul-smelling and greasy (oily) and frothy looking. Many patients confuse steatorrhea with diarrhea but technically it’s a different issue although both issues may present concurrently. Whilst we all need some fat in our diets (e.g. for energy), if a patient is not absorbing fat, it ends up being wasted in their stools and in addition to the steatorrhea, it can also potentially lead to (unwanted) weight loss and micronutrient deficiencies of the fat-soluble vitamins A, D, E and K. Certain water-soluble vitamins, particularly B3 and B12, are also at risk. Many NET Patients are prescribed a supplement of pancreatic enzymes to combat these issues – see Article 5 in this series – Pancreatic Enzyme Replacement Therapy (PERT).
What causes it with NET Patients?
Structural Changes (i.e. Surgery)
This can play a very big part in malabsorption issues. For example, if a patient has undergone Pancreatic surgery, this will most likely effect the availability of pancreatic (digestive) enzymes needed to break down food. Many Small Intestine NET (SI NET) patients will suffer due to the removal of sections of their ileum, an area where absorption of water-soluble vitamins and other nutrients take place. In fact, the terminal ileum is really the only place where B12 is efficiently absorbed. Low B12 is known to cause fatigue. Some patients with Gastric tumours succumb to pernicious anemia with the most common cause being the loss of stomach cells that make intrinsic factor. Intrinsic factor helps the body absorb vitamin B12 in the intestine. Although a less common tumour location, jejunum surgery could result in loss of nutrients as this section of the small intestine is active in digestive processes. Malabsorption issues for SI NETs are an added complication to the issues caused by a shorter bowel (e.g. faster transit time), something which is regularly assumed to be the effects of one of theNET Syndromes (particularly diarrhea and fatigue), when in actual fact, it’s a simple consequence of cancer treatment and may need a different treatment regime.
Evidence of the problems being caused by the effects of small intestinal surgery can be found in a recently published Swedish study which you can read here: Click here. This particular study recommends supplementation of B12 and D3 for those affected. If you’re having trouble getting your physician to monitor your vitamin levels, show them these studies. I get these vitamins checked annually.
The Gallbladder and Liver
The Gallbladder plays an important part in the digestive system – particularly in fat breakdown. The liver continually manufactures bile, which travels to the gallbladder where it is stored and concentrated. Bile helps to digest fat and the gallbladder automatically secretes a lot of bile into the small intestine after a fatty meal. However, when the gallbladder is removed, the storage of bile is no longer possible and to a certain extent, neither is the ‘on demand automation’. This results in the bile being constantly delivered/trickled into the small intestine making the digestion of fat less efficient. One of the key side effects of Somatostatin Analogues (Octreotide and Lanreotide) is the formation of gall stones and many Neuroendocrine Cancer patients have their gallbladder removed to offset the risk of succumbing to these issues downstream. However, the removal of the gallbladder increases the risk of Bile Acid Malabsorption (BAM) as described below. Any issues with Bile Ducts can also have a similar effect.
The Liver has multiple functions including the production of bile as stated above. However, one of its key functions within the digestive system is to process the nutrients absorbed from the small intestine. If this process is affected by disease, it can potentially worsen the issues outlined above.
Bile Acids Malabsorption
Another risk created by the lack of terminal ileum is Bile Acids Malabsorption (BAM) (sometimes known as Bile Salts Malabsorption and some texts described the resultant diarrhea as ‘Bile Acid Diarrhea”). Bile Acids are produced in the liver and have major roles in the absorption of lipids in the small intestine. Following a terminal ileum resection which includes a right hemicolectomy, there is a risk that excess Bile Acids will leak into the large intestine (colon) via the anastomosis (the new joint between small and large intestines). This leakage can lead to increased motility, shortening the colonic transit time, and so producing watery diarrhea (or exacerbating an existing condition).
Somatostatin Analogues can also impact (or worsen) the ability to digest fat as they inhibit the production of pancreatic digestive enzymes (amongst other things). This is a well-known side effect of both Octreotide and Lanreotide. The levels of the fat-soluble vitamins (ADEK) and B vitamins such as B12, need to be monitored through testing and/or in reaction to symptoms of malabsorption. If necessary these issues need to be offset with the use of supplements as directed by your dietician or doctor. Supplements are less affected by malabsorption of nutrients but their efficiency can be impacted by fast gut transit times (thus why testing is important). The evidence and recommendations for malabsorption caused by somatostatin analogues is here: Click Here.
Deficiencies of these vitamins and certain minerals can lead to other conditions/comorbidities, some more serious than others. For a list of the vitamins and minerals most at risk for Neuroendocrine Cancer patients, have a read of my article which was co-authored by Tara Whyand – Vitamin and Mineral deficiency risks.
There is a third article in this series discussing a related issue with Neuroendocrine Cancer, particularly where gut surgery has been performed. You can link directly to this article here – “Gut Health” – (Gut Health, Probiotics and Small Intestinal Bacterial Overgrowth (SIBO)).
The fourth article looks at Amines and why they can cause food reactions or exacerbate syndromes.
Many people also confuse steatorrhea with diarrhea (although these issues can appear simultaneously), again leading to wrong conclusions about the causes and effects, and worryingly, the treatment required. Check out my diarrhea article – click here.
Read a Gut Surgery Diet Booklet authored by Tara – CLICK HERE
A common problem in patients and from what I see, many just assume this is part of their various syndromes leading to the wrong therapy or no therapy as it’s simply ignored. Again, I remain very grateful to Tara Whyandfor some assistance.
This is a big and complex subject and I only intended to cover the basics. Everyone is different and nothing in here should be accepted as medical advice for you or anyone you know. If you need professional advice, you should speak to your doctor or registered dietitian.
Although initially considered rare tumours up until 10 years ago, the most recent data indicates the incidence of Neuroendocrine Neoplasms (NENs) has increased exponentially over the last 4 decades and they are as common as Myeloma, Testicular Cancer, and Hodgkin’s Lymphoma. In terms of prevalence, NENs represent the second most common gastrointestinal malignancy after colorectal cancer. Consequently, many experts are now claiming NENs are not rare (see below).
A recent study published on 5 Dec 2018 reports that even if you isolate Small Intestine NETs in the USA population, the incidence rate is 9/100,000. Contrast this against the US incidence rate as at 2012 of 7/100,000 for all NETs. The rare threshold in Europe is 5/100,000 and below. They’re not common (in incidence rate terms which means the numbers diagnosed each year) but they are certainly no longer rare, a more accurate description would be ‘uncommon’.
However, on 7th January 2019, an internationally known NET Specialist described NETs as very common but he was talking in terms of the prevalence (how many people are living with the disease)
In fact, the graph of the SEER database figures for NETs in both 2004 and 2012 indicates the rate of incidence increase is faster than any other cancer on the planet, particularly attributed to lung, small intestine, and rectal NETs. The World Health Organisation’s revised classification of Neuroendocrine Neoplasms in 2010, abandoned the division between benign and malignant NET as all NETs have malignant potential and should be graded accordingly. The 2004 SEER data compiled did not take into account what might have been considered to be benign NETs.
However, the most recent USA study up to 2012 has confirmed the incidence beyond 2004 has continued to rise (and rise, and rise, and rise) and this is covered below in the section entitled “Meanwhile inUSA”. One of the principal authors of both database studies has now gone public and said NETs are no longer rare.
Incidence and Prevalence
Before I continue, it’s important to understand the difference between incidence and prevalence. In the crudest of terms, incidence is the number of new cases of a disease being diagnosed (normally aligned to a specific quota of the population per year, generally 100,000). Prevalence normally indicates an amount of people living at any one time with a disease. It’s also important to note that different nations or groups of nations classify ‘rare’ in different ways – not really helpful when looking at worldwide statistics.
So why the increase? I suspect the reasons include (but are not limited to), more awareness (population and medical staff), better detection techniques and probably more accurate reporting systems, at least in USA, Norway, Canada and now in the UK i.e. a mixture of underdiagnoses and misreporting. The Canadian study is important as it also noted the proportion of metastases at presentation decreased from 29% to 13%. This is the first study that suggests an increased incidence of NETs may be due to an increased (and earlier?) detection. This has the knock on effect of increasing prevalence as most NET Cancer patients will normally live for longer periods. Add to this the plethora of better treatments available today, you have a highly prevalent cancer. Most of that is good news.
However, their true incidence may be 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. In Australia, one study claimed that 0.05% of all autopsies found a Pheochromocytoma or Paraganglioma. A very interesting slideshow from a well respected NET expert claimed there are 200,000 undiagnosed NET patients in USA. Slide below: You may also wish to check out my article “The Invisible NET Patient Population” where this is explored further.
US SEER 2004 – The Trigger and Turning Point
In the largest study of its kind up to that point, well-known Neuroendocrine Cancer expert James C. Yao researched the Surveillance, Epidemiology and End Results (SEER) database. His team studied 35,825 cases of Neuroendocrine Cancers in the United States covering data between 1973 and 2004. The report concluded that in 2004 there were 5.25 new cases of NETs per 100,000 people, compared with 1.09 per 100,000 in 1973 . This is in contrast to the overall incidence of malignancies, which has remained relatively constant since 1992 (see the yellow line on the graph).The study also pointed out that due to increased survival durations over time, NETs are more prevalent than previously reported. If you analyse the NET data for 1994 (10 years before the end of the study period), you will see an incidence rate of approx 3.25/100,000. In 2004, the incidence rate had risen to 5.25/100,000. Although not an exact science, it does suggest the potential incidence rate at 2014 (10 years after the study period) might possibly have climbed well beyond 6/100,000 and even further if the same rate of increase displayed by the study had continued (spoiler alert – it actually came out as 7/100,000 see below under ‘Meanwhile in USA’). This study also confirmed a prevalence of 103,000 NET patients as at 2004. As this is regarded as the most accurate NET statistic ever produced, it is interesting to note that was at a time when the prognostics for NET were not as good as they are today indicating there must be a very significant increase if extrapolated to the current time. Moreover, this was prior to the WHO 2010 reclassification of NETs so more diagnoses will be counted today that were not counted in 2004. See below to see the significance of this figure (see section ‘Do the math’).
The 2004 data was an astonishing set of statistics – particularly as they were based on 12 year old data. However, there is now new data up to 2012 that overtakes the above-mentioned groundbreaking study and confirmed the incidence is now even higher. See section entitled “Meanwhile inUSA …….”
Rare but collectively common?
Some will claim that some of the individual types of Neuroendocrine Neoplasm are rare so the disease is rare. That’s clutching at straws really, there’s a rare type of breast cancer but that disease is hardly rare. On that subject let’s talk about something no-one really talks about, Small Cell Lung Cancer (SCLC) which is a type of Neuroendocrine Carcinoma. On it’s own this type is not rare (around 15% of all cancers of the lung).
I suspect on their own, these types of Neuroendocrine Tumours are rare based on the numbers but things are changing. Check out this short video clip from the Pheo/Para Alliance. Let’s do some maths: Based on the US population of 320,000,000, that’s 106,666.
A few more facts about Pheochromoctyoma/Paraganglioma:
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).
Here is an article claiming that former US President Dwight D Eisenhower had a biopsy confirming he had a Pheochromocytoma. Click here.
Meanwhile in Norway ……
Data from the Norwegian Registry of Cancer showed a similar incidence of Neuroendocrine Cancers with a 72% increase between 2000 and 2004 compared with 1993–1997. Also in Norway, an article published in 2015 entitled “Epidemiology and classification of gastroenteropancreatic neuroendocrine neoplasms using current coding criteria” indicated a high crude incidence of GEP-NEN, at 5·83 per 100 000 inhabitants over the period 2003-2013 (adjusting to 7.64 for Europe in 2013 – see diagram below extracted from cited article 2a). It was also noted together with the statement “….a significant increasing trend over time”. [2a] Citation [2b]
Meanwhile in Canada …….
CNETs have highlighted an article published in the magazine ‘Cancer’, February 15, 2015, showing that the incidence of Neuroendocrine Tumours has markedly increased in Canada over the course of 15 years (1994-2009). The results showed that the incidence of Neuroendocrine Tumours has increased from 2.48 to 5.86 per 100,000 per year. 
Meanwhile in UK …….
The latest figures from Public Health England (PHE) indicate the incidence of NETs has risen to almost 9/100,000 (i.e. not rare) using the latest International Classification of Diseases for Oncology (ICD-O) methodology version 3 – ICD-O-3. Even that figure is understated because it does not include Lung Neuroendocrine Carcinomas (i.e. SCLC and LCNEC). As at 31 Mar 2016, the age-standardised incidence rate for NETs in England (excluding small and large cell neuroendocrine carcinomas, SCLC and LCNEC respectively) was 8.84, 8.37 in males and 9.30 in females – rising from 3.9 in 2001. These figures are from the NET Patient Foundation and were issued as a result of a NPF and PHE (NCRAS) partnership project which has been compiling statistics on the incidence, prevalence and survival of NET Patients in England using English cancer registry data. They also have an aim to also access the rest of UK cancer registry data to get UK wide figures.
A slide from the recent UKINETS 2017 conference indicating an agreement from UK and Ireland NET Specialists.
Meanwhile in New Zealand …….
Meanwhile in USA …….
The latest evidence of its rise is contained in the largest ever study ever conducted. It is based on data up to 2012 so it’s worth noting that in 2019, this data is now 7 years old (5 years for the project prevalence figure), so even these figures may still be conservative. The document, which was published in 2017 can be found here: Click here. A short summary follows:
In this population-based study that included 64 971 patients with neuroendocrine tumors, age-adjusted incidence rates increased 6.4-fold between 1973 and 2012, mostly for early stage tumors. Survival for all neuroendocrine tumors has improved, especially for distant stage gastrointestinal and pancreatic neuroendocrine tumors.
Of the 64 971 cases of NETs, 34 233 (52.7%) were women. The age-adjusted incidence rate increased 6.4-fold from 1973 (1.09 per 100 000) to 2012 (6.98 per 100 000). This increase occurred across all sites, stages, and grades. In the SEER 18 registry grouping (2000-2012), the highest incidence rates were 1.49 per 100 000 in the lung, 3.56 per 100 000 in gastroenteropancreatic sites, and 0.84 per 100 000 in NETs with an unknown primary site. The estimated 20-year limited-duration prevalence of NETs in the United States on January 1, 2014, was 171 321
Conclusion: The incidence and prevalence of NETs have continued to rise in the United States, owing to the increased diagnosis of early-stage disease and possibly stage migration. The survival of patients with NETs has improved, and this improvement has been greater for those with distant gastrointestinal NETs and, in particular, distant pancreatic NETs.
Combine that with a revised annual incidence rate of 23,000 and the very well known fact that NETs is a highly prevalent disease, it must be mathematically impossible for the figure not to be above the USA rare threshold of 200,000 in 2017. As you can see from the graph below, the incidence rate for NETs continues to outstrip the incidence rate for all malignant neoplasms (another word for tumour). Amazingly, the report authors even state “…….. it is likely that we have underestimated their true incidence and prevalence”.
The NET Research Foundation published an amazing infographic which summarises the output of the SEER 2012 study (although it does omit the prevalence figure ‘as at’ date). See it below and you can read the accompanying text here.
Let’s do the Math
Neuroendocrine Cancer is not only the fastest growing cancer in incidence terms but as a group of cancers, given the mounting epidemiological evidence, it can no longer be rare as a grouping of cancers. Neuroendocrine disease IS NOT RARE.
For example, if you roughly extrapolate the US SEER data graph above to 2017 and recalculate the prevalence rate based on 23 000 per year from the 2014 figure of 171 321. Unfortunately, some people will have passed, but it’s well documented as a highly prevalent cancer and therefore more people live. The prevalence of neuroendocrine tumors in USA was higher than the combined estimated prevalence of esophageal cancer (n = 36,857), gastric adenocarcinoma (n = 79,843) and pancreatic adenocarcinoma (n = 49,620) in 2013. In fact, one of the conclusions of the 2012 SEER report is that we are living longer with NETs. This is in line with many other cancers due to improved diagnostic and treatment regimes. Cleary more work still needs doing.
The heading of this section is my name for those who have not yet been diagnosed with NETs but are walking around having been either misdiagnosed, diagnosed with another cancer in the same part of the anatomy, living and putting up with the symptoms whilst the tumours grow. Read my Invisible NET Patient Population article here. To add to this part of the underdiagnoses of NETs 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. DOI: 10.1158/1078-0432.CCR-17-3378. This was a pan cancer piece of research which indicated that Neuroendocrine disease may be more prevalent than anyone had ever thought. There’s a summary article here which I suggest you read fully. The rather explosive extract is as follows:
Whilst reporting has been improved, it is most likely still not 100% accurate. Therefore, even the figures above may be understated due to an incorrect cause of death reporting and incorrect diagnosis/recording of the wrong cancers (e.g. pNETs recorded as Pancreatic Cancer, Lung NETs recorded as Lung Cancer, etc). This is certainly still happening in UK and I suspect in most other countries. Add to that the regular reports of Neuroendocrine Tumours being found during autopsies and you have the potential for an even further unrecorded increase had these been found prior to death. In fact, according to SEER 2012, the true incidence and prevalence is most likely underestimated. In fact here is a statement straight from the horse’s mouth:
The issue is also complicated by the method used in USA for naming a disease ‘rare’. Rather than use incidence rates, the USA uses the number of people living with the disease at any one time (i.e. essentially the prevalence). This is currently 200,000 as a threshold – anything below that is considered rare. It seems mathematically impossible for NETs to be less than 200,000 given the data provided above.
When I first started researching NETs back in 2010, the US figure (which varies from source to source) was around 125-150,000. Why are people quoting figures less than this in 2017 when the 2014 figure has now been confirmed above? There also seems to be a selective omission of the new US incidence rate of 7/100,000.
You will also see that Dana Farber is estimating more than 200,000 people are as yet undiagnosed. Even if that were 50% accurate, it would put the current prevalence figure in US over 300,000.
Let’s cut to the chase – NETs are not rare, they are just less common
Are we shouting loud enough about this? I don’t think so. ‘Rare’ is very frequently used within the NET community almost to the point of being a status symbol. Based on these figures, this looks like an outdated approach along with its associated icons. The evidence above is so compelling that saying the group of cancers officially called Neuroendocrine Neoplasms is rare is starting to sound like fake news.
“A neoplasm on the rise. More prevalent than you may think. Incidence increased dramatically during past 3 decades” (Novartis)
“it’s less rare than we used to think. It’s more malignant than we previously thought” (Dr Richard Warner)
“…..it is one of the most rapidly increasing cancers in the U.S. There has been a 500-percent increase in the last 30 years” (Dr Edward Wolin)
“Estimated more than 200,000 undiagnosed cases in the US” (Dana Farber)
“I actually think NETs are not a rare cancer” (Dr James Yao)
“NETS will no longer be rare” (UKINETS 2017 one of the opening slides)
“NETs are no longer rare” (Dr Andrew Hendifar)
“…..when you think of prevalence, NETs are actually quite common” (Dr Jonathan Strosberg)
“One study showed that the number of people diagnosed has risen 50% over the last decade and unfortunately, I worry that is an underestimate” (Dr Eric Liu)
“Neuroendocrine Cancer – NETs are not rare, just less common. We need a new paradigm” (Ronny Allan since 2015)