OPINION – nothing in here should be taken as advice from the author.
On paper, surgery remains the only potentially ‘curative‘ option for Neuroendocrine Tumours (NETs) but there are stage, grade and anatomical constraints to that opinion. Many people get ‘twitchy’ about any inference of the ‘C word’ (cure) but our most eminent NET specialists use the term frequently including in the major treatment guidelines.
I use the word ‘curative’ with some reservations because for many who are diagnosed at an advanced stage, surgery will not cure but will debulk or cytoreduce as much tumour as possible in order to palliate symptoms and improve quality of life. This is a big deal because NETs is one of a small number of cancers where debulking surgery can often provide a survival advantage for metastatic cases. One of the reasons it’s a big deal is because with more aggressive cancers at an advanced stage, surgery just might not be offered. It follows that surgery is most likely adding to the fairly decent NETs survival statistics, including for those with metastatic disease at diagnosis. More on this below.
That’s a fairly simplistic explanation on behalf of surgery. However, as we all know, nothing in Neuroendocrine Cancer is simple. There are always a number of factors involved and every decision can in some way be on an individual basis. There are guidelines for treatment of most types of NETs but ……. they are just that – guidelines. NET Centres and NET Specialists are encouraged to use these guidelines, for example, a European Centre of Excellence has ENETS Guidelines. There is a North American equivalent set published by NANETS and NCCN have a decent complementary set. The UK and Ireland guys (UKINETS) also published a set although many UK centres are ENETS accredited.
Whether to cut or not to cut (or watch and wait then cut if necessary) and the sequencing of treatments is a really difficult issue for NET specialists. I quite liked watching these two video clips and they cover this issue quite nicely including some interesting abdominal challenges in surgery from known NET Specialists – these short video sessions are highly recommended:
a. Risk Stratification and Management of NETs – click here
Surgery can sometimes be a tough call (……to cut or not to cut?)
It is an area where I have some sympathy for physicians and surgeons who sometimes have tough decisions to make. Surgery is risky, particularly where people are presenting in a weak condition, perhaps with very advanced disease, secondary illness and comorbidities. I also suspect age is a factor (I was surprised to find myself considered ‘young’ at 55). Physicians and surgeons need to weigh up these risks and the consequences of the surgery against a ‘watch and wait’ or alternative non-surgical approach. This would normally be discussed via a ‘Tumor Board’ or Multi-Disciplinary Team (MDT) meeting. However, and although imaging helps, the situation is not really 100% clear until the surgeon ‘gets inside’. Remember, all physicians and surgeons are bound by the ‘Hippocratic oath’ of “Do no harm“. Sometimes with NETs, it’s a tough call not only before they go inside but whilst they’re inside.
Surgery should be a carefully considered treatment (…..think before cutting?)
I read many stories from many different parts of the world and I also hear them from people who contact me privately on a daily basis. Some of them are perplexed why they are not receiving surgery and some are not entirely happy with the surgery they received. Many are perplexed by different advice from different doctors. I find it very difficult to respond to many. My most frequent answer is “ask your doctor” but I’m normally pretty helpful with the sorts of questions to ask.
One thing which tends to surprise people is speed – or lack of it! With lower grade NETs, the extent of the tumour (stage), its metastases, histological grade and secretory profile should be determined as far as possible before planning treatment. I like to remind people that in 2010, it took from 26 July to 9 Nov before my body saw a scalpel. With Grade 1/2 well differentiated NETs, you can often get away with that gap. Sometimes when you are diagnosed with NET, it’s a case of ‘hurry up and wait’.
Back to the guidelines, of course most people will probably fit reasonably well into the relevant guidelines flow chart. A very generic example here (not for active use please, your area may have an alternative based on availability of treatments etc):
If you search long and hard, you will find articles about whether to “cut or not to cut”. Not just a dilemma for NETs but also for many cancer types. During my research, I found there’s some overlap between this conundrum and the issue of “overdiagnosis”. By “overdiagnosis”, I mean the unnecessary declaration and treatment of something which would probably not harm a person whilst they live. This is a bit of a modern phenomena as diagnostic tools and screening programmes become more sophisticated and more sensitive …..something to consider with Ga68 PET scans as they are more widely used. If you search for ‘overdiagnosis’ you will see many articles, in particular (and as an example), with many Thyroid diagnoses. In another example, I read an article about Rectal cancerwhere the author suggested a ‘wait and see’ approach might be better for most. Worth adding at this point that many autopsies show up NETs in areas such as the appendix (…..more often than you think) – check out my article “Benign vs Malignant” and The Invisible NET Patient Population. When I attended ENETS 2017 and 2018, I heard many ‘experts’ talk about conservative approaches. However, I also heard many talk about aggressive approaches. Another term I see a lot is “one surgeon’s inoperable is another’s operable”.
Timing of Surgery (……to cut now, to cut later?)
Following on from the scenario above, timing of surgery can be another factor in a ‘watch and wait’ situation. I guess this might be something in the back of the minds of more cautious doctors when faced with a rather indolent and very slow growing Neuroendocrine Tumour. For some this can be a sensible thing – ‘kicking butt’ in a surgical context is sometimes the wrong approach. The worry is that if they are not a NET specialist, they may not fully understand the vagaries of neuroendocrine tumor behaviour (i.e. they all have malignant potential – WHO 2010/2017). We’ve all heard the stories of people being told it’s not cancer, right? Please note my article Benign vs Malignant. However, you may be interested in this post from someone who is one of the most experienced NET surgeons on the planet. Dr Eric Liu talks quite candidly about the ‘timing’ of surgery suggesting a ‘watch and wait’ approach in certain scenarios.
Of course cutting now might actually be a pre-emptive measure. For example, if physicians can see a growth which is critically placed close to an important structure such as a blood vessel or the bile duct or bowel. Even if the disease cannot be cured, removing the tumour may prevent problems in the future by removing disease from key areas before the vital structure has been damaged or blocked. For example, my surgeon conducted a high risk operation on some desmoplasia (serotonin fibrosis) which had encircled my aorta and cava almost occluding the latter. There’s an excellent surgery pamphlet from NET Patient Foundation and I strongly recommend a read as it’s an experienced surgeon’s approach to surgery with NETs (actually written by my own surgeon Mr Neil Pearce!). Click here to read it.
One NET centre in USA has published very detailed surgical statistics indicating that surgical cytoreduction in NET patients has low morbidity and mortality rates and results in prolonged survival. Their conclusion went on to say “We believe that surgical cytoreduction should play a major role in the care of patients with NETs”. You can read the extract from this document by clicking here. Authors: Woltering et al.
Was Steve Jobsa smart guy who made a stupid decision when it came to his health? It might seem so, from the broad outlines of what he did in 2003 when a CT scan and other tests found a cancerous tumour in his pancreas. Doctors urged him to have an operation to remove the tumour, but Mr. Jobs put it off and instead tried a vegan diet, juices, herbs, acupuncture and other alternative remedies. Nine months later, the Neuroendocrine Tumour had grown. Only then did he agree to surgery, during which his doctors found the cancer had spread to his liver. The rest is summarised in my article Steve Jobs.
This is a difficult subject and no one size fits all. Treatment for NETs can be very individual including surgery. I guess you need to be comfortable with your team. I was lucky, in that I lived close to a NET Centre. I was referred to their surgical team once my staging and grading were complete and I was stabilised on somatostatin analogues (carcinoid syndrome under control). I realise it’s difficult for many but I always say to people who make contact, it’s best if you can be seen by a NET centre or an experienced NET specialist – at least be guided by one if not possible or practical. Personally, I think the surgeon’s experience in dealing with NETs is really important. But even experienced NET centres/specialists have to make tough calls.
You may benefit from my 10 Questions article which also has links to NET Specialists.
In 2013, just when I thought everything seemed to be under control, I was told I had a ‘lesion’ on the left upper lobe of my thyroid. At the time, it was a bit of a shock as I had already been subjected to some radical surgery and wondered if this was just part of the relentless march of metastatic NET disease. The thyroid gland does in fact get mentioned frequently in NET patient discussions but many of the conversations I monitored didn’t seem to fit my scenario – cue relentless study! I’ve been meaning to write this blog for some time but here is a synopsis of my research translated into ‘patient speak’. This is intentionally brief, it’s a big subject. I’ll finish off with an update on where I am with my thyroid issue.
Where is the thyroid and what does it do?
Before I found out about my thyroid problem, I had absolutely no idea what its function was. I can tell you know, it’s a small organ but it has a massive job!
It lies in the front of your neck in a position just below your ‘Adam’s apple’. It is made up of two lobes – the right lobe and the left lobe, each about the size of a plum cut in half – and these two lobes are joined by a small bridge of thyroid tissue called the isthmus. It is sometimes described as butterfly shape. The two lobes lie on either side of your wind-pipe. The fact that it comes up a lot in NET patient discussions is hardly surprising as it’s an endocrine organ responsible for making two hormones that are secreted into the blood: Thyroxine (T4) and Triiodothyronine (T3). These hormones are necessary for all the cells in your body to work normally.
Do I have Thyroid Cancer?
I’ve had a number of biopsies on the thyroid lesion, several fine needle aspiration (FNA) and one ‘core’. The FNAs were generally inconclusive and the core confirmed fibrous tissue only. However, the general diagnosis is inconclusive and I have been labelled “THY3F”. Curiously this decodes to “an abnormality is present but it could either be a benign (non cancerous) growth or a malignant cancerous growth of the follicular cells. A quick primer on Thyroid Cancer is below if you’re interested.
It’s easy to worry about irregularities showing up on scans if you have NETs. Take the thyroid for example, the Ga68 PET has a habit of ‘lighting up’ thyroids – this is a worry because it’s an endocrine organ; and there is a type of thyroid NET (not forgetting the parathyroid), and NETs have a habit of metastasizing to strange places. Sure, you should get it checked out when this happens, but while you will only hear about the outliers on social media, statistically, the vast majority of thyroid nodules are benign. We know about ours because we get so many scans but many people will probably never know and will probably never be bothered by them either. When you look at the figures below, it becomes clear that many NET patients are going to have a thyroid nodule regardless of their diagnosis.
The following is a list of facts regarding thyroid nodules:
Thyroid nodules are three times more common in women than in men
30% of 30-year-old women will have a thyroid nodule.
One in 40 young men has a thyroid nodule.
More than 95% of all thyroid nodules are benign (non-cancerous growths).
Some thyroid nodules are actually cysts, which are filled with fluid rather than thyroid tissue.
Purely cystic thyroid nodules (thyroid cysts) are almost always benign.
Most women will develop a thyroid nodule by the time they are 50 years old.
The incidence of thyroid nodules increases with age.
50% of 50-year-old women will have at least one thyroid nodule.
60% of 60-year-old women will have at least one thyroid nodule.
70% of 70-year-old women will have at least one thyroid nodule.
Fear of spread
It’s easy to be concerned about irregularities showing up on scans if you have NETs. However, the Ga68 PET has a habit of ‘lighting up’ thyroids and this is a double worry because it’s an endocrine organ, and there is a type of thyroid NET (not forgetting the parathyroid). But it eventually became clear through research that most are unconnected. Sure, you should get it checked out, but while you will only hear about the outliers on social media, the vast majority of cases are benign. If you constantly fear cancer spread with every single issue you undergo as a human being, you probably need some help. You may therefore find my ‘fear’ articles a useful read plus there are two videos presented by professionals who help caner patients cope with these issues:
Thyroid overdiagnosis and overtreatment. You can find many medical papers confirming that incidence of thyroid tumour diagnosis has increased dramatically in many countries in the developed world over the past three decades. Papillary thyroid cancer, which has been responsible for virtually the entire increase, is rarely lethal. The 20 year survival rate is greater than 90%, and approaches 100% for the smallest cancers. The increasing incidence is most likely due to overdiagnosis—the detection of subclinical cancers never destined to cause harm. This conclusion has been reached because the incidence has been primarily due to the detection of small papillary cancers, mortality due to thyroid cancer has not changed significantly, and small foci of papillary thyroid cancer are commonly found at autopsy in people who died of other causes. Overdiagnosis is a problem because it exposes people to the potential side effects of treatment, but without an equal expectation of benefit, because the cancer is unlikely to advance. We know about ours because we get so many scans.
Issues above the diaphragm
There can be other issues with Thyroids including cancer and clearly this was my concern when the word ‘lesion’ was mentioned. At this point, it’s worth mentioning something from my cancer history which I initially assumed was related but it would appear to be a coincidence (for the time being …..). When I say “above the diagphragm”, I mean above the abdoment in the general neck and chest area. I also have a hotspot in my left supraclavicularfossa (SCF) lymph nodes (near the clavicle), geographically close to the thyroid (and my lesion is left-sided). 5 nodes were removed from this area in Feb 2012 for an exploratory biopsy which subsequently tested negative and CT and Ultrasound both show nothing vascular or pathologically enlarged. BUT …. there is still a hotspot showing on a subsequent Octreoscan and Ga68 PET since the nodes were removed in 2012. For the record, I also had positively tested nodes removed from my left axillary (armpit) during the same procedure (my distant disease has always been left-sided).
The surgeon who operated on my left axillary and SCF nodes also specialises in Thyroids and so it was an easy decision to ask to be referred to him. He explained that whilst he could just take the left lobe or the whole thyroid, it would mean lifelong treatment to add to my current burden and perhaps for something which will never trouble me. As nothing is palpable and I have no symptoms, I agreed to a ‘watch and wait’ approach. I now have regular tests and I saw him Endocrine MDT annually for a blood test review and ultrasound check (but see update below).
See EndocrineWeb for more detail about thyroid issues unrelated to NET.
Latest update as at 15 Jan 2019
After monitoring for the first two years, my specialist was not happy with TSH/T4 blood results (elevated for the second time and also on a retest). On 20 March 2018, following an Endocrine appointment, I was put on a trial dose of 50mcg of Levothyroxine to counter the thyroid panel results indicating mild hypothyroidism. Levothyroxine is a thyroid hormone replacement. My subsequent two x thyroid panel results are back in the middle of the range so all is good. Am detecting a slight increase in available energy.
The results of my first Ga68 PET scan in June 2018 indicated some “uptake” but the report inferred it was physiological uptake (false positive). In fact, at my 2019 appointment, the thyroid lesion is slightly smaller on the latest ultrasound. I’m personally fairly certain this is not connected to NETs and my Endocrine MDT have now referred me back to be survellanced by the NET MDT, they remain on call for any issues.
What else can go wrong with a thyroid?
Apart from cancer, the main issues appear to be an underactive Thyroid or an overactive Thyroid – known respectively as Hypothyroidism (not enough thyroxine is produced for the body’s needs) and Hyperthyroidism (too much thyroxine is produced for the body’s needs). Of course, these issues can be caused or made worse by cancer.
Hypothyroidism – If too little of the thyroid hormones are produced, the cells and organs of your body slow down. If you become hypothyroid, your heart rate, for example, may be slower than normal and your intestines work sluggishly, so you become constipated. Key symptoms: tiredness, feeling cold, weight gain, poor concentration, depression. Some of these symptoms look familiar? The word ‘hashimoto’s’ also comes up on patient forums frequently – this is related to hypothyroidism (underactive).
Hyperthyroidism – If too much of the thyroid hormones are secreted, the body cells work faster than normal, and you have Hyperthyroidism. If you become hyperthyroid because of too much secretion of the hormones from the thyroid gland, the increased activity of your body cells or body organs may lead, for example, to a quickening of your heart rate or increased activity of your intestine so that you have frequent bowel motions or even diarrhoea. Key symptoms – weight loss, heat intolerance, anxiety, and, sometimes, sore and gritty eyes. Hmm, again, some of these look familiar?
Check out this excellent short video fromWebMD – click here. It’s based on USA but most of it is relevant globally.
It’s also worth noting thatsomatostatin analoguesmight cause a “slight decrease in Thyroid function” (it actually states words to this effect in the Lanreotide and Octreotide patient leaflets). Thus why I advise you not to be underactive with your Thyroid surveillance – read more click here
Routine ‘Thyroid blood tests’ from your doctor will confirm whether or not you have a thyroid disorder. I now test for TSH (thyroid-stimulating hormone), T3 and T4 every 6 months. My levels are back to normal ranges since being prescribed thyroid hormone replacement therapy.
Remember: Hypo is ‘underactive’, Hyper is ‘overactive’. Sometimes there are very few symptoms.
Also worth mentioning something called the ‘Parathyroid’ as these glands can frequently be related to NET Cancer (see my blog on Multiple Endocrine Neoplasia(MEN)). It’s another subject in its own right but I just wanted to emphasise that this is a totally different organ with a totally different function (it regulates Calcium). They are located adjacent to the Thyroid, thus the term ‘para’.
Quick primer on Thyroid Cancer
There are a number of different types of Thyroid Cancer
Papillary thyroid cancer is the most common type of thyroid cancer, accounting for about 80% of thyroid cancers. While papillary thyroid cancer typically occurs in only one lobe of the thyroid gland, it may arise in both lobes in up to 10% to 20% of cases. Papillary thyroid cancer is most common in women of childbearing age. It sometimes is caused by exposure to radiation. Even though papillary thyroid cancer is usually not an aggressive type of cancer, it often metastasizes (spreads) to the lymph nodes in the neck. Papillary thyroid cancer treatment usually is successful.
Follicular thyroid cancer accounts for about 10% of thyroid cancers. Like papillary thyroid cancer, follicular thyroid cancer usually grows slowly. Its outlook is similar to papillary cancer, and its treatment is the same. Follicular thyroid cancer usually stays in the thyroid gland but sometimes spreads to other parts of the body, such as the lungs or bone. However, it usually does not spread to lymph nodes. It is more common in countries where diets do not contain enough iodine.
There is a type of thyroid tumour which has recently been removed as a type of cancer. “Encapsulated follicular variant of papillary thyroid carcinoma” is now known as “noninvasive follicular thyroid neoplasm with papillary thyroid-like nuclear features” or NIFTP. The word ‘carcinoma’ has gone. Read about this here.
Hurthle cell carcinoma, also called oxyphil cell carcinoma, is a type of follicular thyroid cancer. Most patients diagnosed with Hurthle cell cancer do well, but the outlook may change based on the extent of disease at the time of diagnosis.
Medullary thyroid cancer (MTC) is the only type of thyroid cancer that develops in the parafollicular cells of the thyroid gland. It accounts for 3% to 10% of thyroid cancers. Medullary cancer cells usually make and release into the blood proteins called calcitonin and/or carcinoembryonic antigen, which can be measured and used to follow the response to treatment for the disease. Sometimes medullary cancer spreads to the lymph nodes, lungs or liver before a nodule is found or the patient has symptoms. MTC can be treated more successfully if it is diagnosed before it has spread. There are two types of MTC:
Sporadic MTC is more common, accounting for 85% of medullary thyroid cancers. It is found mostly in older adults and is not inherited.
Familial MTC is inherited, and it often develops in childhood or early adulthood. If familial MTC occurs with tumours of certain other endocrine organs (parathyroid and adrenal glands), it is called multiple endocrine neoplasia type 2 (see my blog on MEN 2).
Anaplastic thyroid cancer is the most dangerous form of thyroid cancer. It is makes up only 1% of thyroid cancers. It is believed that anaplastic thyroid cancer grows from a papillary or follicular tumour that mutates further to this aggressive form. Anaplastic thyroid cancer spreads rapidly into areas such as the trachea, often causing breathing difficulties. Anaplastic thyroid cancer sometimes is called undifferentiated thyroid cancer because the cells are so different from normal thyroid tissue.
Thyroid cancer is not very common but diagnoses are ‘skyrocketing’ most likely due to advanced detection techniques. Most are very slow-growing with 5 year survival of 97% according to MD Anderson. There is a very interesting article about the overdiagnosis of Thyroid cancer which I found useful given my situation. You can read it here.
Thyroid ‘nodules’ would appear to be very common with 50-70% of all 50-70 year olds having at least one nodule present and statistically, 95% of these are benign (see EndocrineWeb)
‘Diagnosis‘. The dreaded moment when you’re looking at an Oncologist and waiting to be given some news. I’d been to a routine annual Asthma clinic, referred to my GP, referred to a specialist, had a bunch of tests and now referred to an Oncologist.
Rewind 2 months to May 2010…… I was happily working, getting stuff done, making things work. I had sufficient autonomy and freedom of manoeuvre. I felt in control. I’m happy as a pig in the proverbial! My annual Asthma clinic comes along and it’s an opportunity to work at home for the day….yahoo – no commuting! “Hi Ronny” – “Hi Liz”. Blah Blah Blah. However, glad Liz was taking it seriously – I just wanted to get back to my laptop, things to do…… After the usual tests and checks, we commenced the AOB (any other business) – “I think I’m a bit lighter than I thought I was”….”Did you mean to lose the weight?”…..”no”. Just to be sure, Liz gave me a blood test form. Had I known at the time that this was probably the most important document I might have ever held in my hand, I would have driven straight down to Bournemouth Hospital and had the test done. However, that form sat in my in-tray for around three weeks…… I was too busy on my laptop, things to do…….. To cut a long story short, my blood results were not right and the discrepancy needed further investigation. I even went on holiday to Barbados not thinking anything was wrong. In hindsight, I’m glad I didn’t know. One thing led to another and on 26 July 2010 I met with an Oncologist. He dispensed the news that I had a metastatic and incurable Cancer and without treatment I would eventually die and perhaps pretty soon (…. I did ask!). p.s. I’m still here though!
I no longer felt in control
But thank you Liz – I often think what might have transpired without that blood test.
Listen to me explaining my diagnosis here: CLICK for the video.
Check out my entire diagnostic, therapy and surveillance story here.
The picture below is me in Barbados a month before I was diagnosed. Glad Chris and I didn’t know what was coming, we had a great time. My ‘hamster cheeks’ are no longer there!