OPINION:

“Cured” – In cancer, this word can evoke a number of emotions. Interestingly, not all these emotions will be as positive as you might think. If you want to spark a heated debate on a Neuroendocrine Cancer patient forum, just mention that you’ve been cured. I’m not taking any sides by using this statement, just stating what actually happens and the deeply held views that persist in community groups. One important factor in some of this thinking is that many people still remember the days where most diagnoses were late and many followed years of misdiagnoses for other conditions. But the latest statistics (and even these can be said to be quite old) indicate things are changing. The massive increase in incidence rates indicates earlier diagnoses and it’s true for many cancers, including Neuroendocrine, that this vastly increases the chances of a cure.

I’ve been living with Neuroendocrine Cancer since 2010 (I guess I had it some years before), so I must be cured, right? Unfortunately, not as straightforward as this, and I’m guessing this is also the case for many cancers. Doctors are faced with word challenges daily because patients understandingly cling to certain words for which they interpret perhaps different than a doctor. Doctors, therefore, need to be careful when saying the word “cured‘ even if there is a small likelihood that cancer will recur. Even the word ‘curative’ in relation to therapy needs to be carefully contextualized.

Cure vs Remission

Your cancer is in complete remission when, after treatment, no cancer can be detected. The term “cure” can only be used in hindsight. Commonly, years after the cancer has gone into remission, if it has not returned (or relapsed), it is said to have been cured.  This period may differ between different cancers and between different grades (degrees of aggressiveness) of cancer.  However, a secondary cancer could occur if the same conditions that triggered the first are present.  Read more here how this might apply to Neuroendocrine Cancer.

Cancer can only really be cured if every cancer cell is dead but it’s difficult to know if that’s the case due to our inability to detect small amounts of cancer. A skilled specialist may be able to feel a breast lump that is half a centimetre wide. A plain chest X-ray can be expected to detect cancers from 1cm wide. And a CT scan will detect smaller cancers to a few millimeters.

But a cancer 1cm across on a scan has about 100 million cancer cells; even a 0.5cm cancer has about 10 million cells. A 1mm cancer, which would not show up on scans, has 100,000 cancer cells. So, even when a cancer can no longer be seen and is no longer causing symptoms, there can still be millions of cells remaining. They have the potential to keep growing and eventually, the cancer will be large enough to be detected again. That’s called relapse.

Remission periods can be different, e.g. aggressive cancer which grows fast would need a shorter surveillance time than a slow-growing one.  Epidemiological data guides doctors on what is likely to happen and therefore to manage their patients.  Worth pointing out that in the 1970s, only one cancer patient in three made it through the first five years after diagnosis. Today, this figure is around 70-85%. Remission is linked to time.

There’s plenty of ‘conservative’ and ‘safer’ alternative terms that can be used, such as ‘stable’, ‘no evidence of disease (NED)’, ‘in remission’ or ‘complete response’. However, to be truthful, I don’t see the latter two much in Neuroendocrine disease anecdotally.

• Cure means that there are no traces of your cancer after treatment and your cancer will never come back.
• Remission means that the signs and symptoms of your cancer are reduced. Remission can be partial or complete. In complete remission, all signs and symptoms of cancer have disappeared.
• If you remain in complete remission for 5 years or more (could be less for more aggressive types), some doctors may say that you are cured. Still, some cancer cells can remain in your body for many years after treatment. These cells may cause cancer to come back one day.
• For cancers that return, most do so within the first 5 years after treatment. But there is a chance that cancer will come back later. For this reason, doctors cannot say for sure that you are cured. The most they can say is that there are no signs of cancer at this time. Sometimes this is called No Evidence of Disease (NED)
• Because of the chance that cancer can come back, your doctor will monitor you for many years and do tests to look for signs of cancer’s return. They will also look for signs of late side effects from the cancer treatments you received.  In my opinion, there is pragmatism in both remission and NED statuses in the absence of science which does not exist yet. 

So, with all these ‘ifs’ and ‘buts’, can we actually cure Neuroendocrine Cancer?

Answering this question isn’t a simple case of ‘yes’ or ‘no’, because it depends on the way that the term ‘cancer’ is defined. It should actually be viewed as an umbrella term for a collection of hundreds of different diseases. They all share the fundamental characteristic of rogue cells growing out of control, but each type of cancer, and each person’s individual cancer, is unique and comes with its own set of challenges. That doesn’t mean individual cases of cancer can’t be cured.  Cancer is seen today less as a disease of specific organs, and more as one of molecular mechanisms caused by the mutation of specific genes. The implication of this shift in thinking is that the best treatment for, say, colorectal cancer may turn out to be designed and approved for use against tumors in an entirely different part of the body, such as the breast. We’re certainly seeing that with certain targeted therapies and more recently with Immunotherapy.

Given the above, it’s very unlikely that there will be one single cure that can wipe out all cancers, well at least not right now. Scientists aren’t actually on the hunt for a ‘silver bullet’ against all cancers, Quite the opposite. The more scientists get to know each type of cancer inside and out, the greater the chance of finding new ways to tackle these diseases so that more people can survive. Thanks to a much deeper understanding of cell biology and genetics, there exist today a growing number of targeted therapies that have been designed at a molecular level to recognise particular features specific of cancer cells. Along with chemotherapy, surgery and radiotherapy, these treatments—used singly and in combination—have led to a slow, but steady, increase in survival rates. You can definitely count Neuroendocrine Cancer in that category.

There are many diverse types of Neuroendocrine Neoplasms (NEN), so when you look at the general cancer descriptions above, a cure for one type of Neuroendocrine Cancer may not necessarily cure other types – e.g. well-differentiated and poorly differentiated NENs.   However, epidemiological data confirms that some types of NEN can be treated with curative intent and their cancer will never come back after a short period of surveillance.  Epidemiological data also confirms that certain types have a higher recurrence or relapse than others.   Even at Stage 4, where this is a synonym for terminal cancer in cases of a very aggressive disease, it is not the same ‘red flag’ it is for low-grade NETs which may also be incurable, but they are certainly treatable much like a chronic illness. 

Surely a cure is more possible if Neuroendocrine cancer is diagnosed earlier?

To a certain extent this is true for many types of cancer, including Neuroendocrine Neoplasms (I refer you to my statement on the increase in incidence rates above). In fact, the scientists I quoted below did say ….”We detect those attacks when they’re still early, before the cancers have widely spread, at a time when they can still be cured simply by surgery or perhaps surgery and adjuvant therapy, which always works better on smaller tumors.”.

What about Neuroendocrine Neoplasms (NENs)? Clearly, I’m not qualified to make such statements except to say that I am of the opinion that earlier diagnosis is better for any curative scenario. When you read NEN guidelines (ENETS/NANETS etc), the word ‘cure’ and ‘curative’ is frequently mentioned in relation to surgery. Bearing in mind that our most expert specialists are involved in the drafting of these guidelines, perhaps we should pause and think before dismissing these claims. Having checked ENETS publications, I can see it’s related to certain conditions and factors such as localisation within the organ, tumour size, good resection margins, and suitable follow-up surveillance.

Clearly with advanced disease, cancer becomes incurable but treatment for many being palliative to reduce tumor bulk and reduce any symptoms and/or syndrome effects. Despite this, the outlook for metastatic NENs at the lower grades is good. While we’re talking about palliative care, do not confuse this with end of life, that is only one end of the palliative spectrum. It can and is used at the earliest stage of cancer.

What I do know is that there are people in patient support groups who are too quick to say “NETs cannot be cured” without checking on the original poster’s type of NET, grade/ki67 and stage.  I’m fairly certain that many people with low stage, low Ki67 with localised (isolated) primaries in certain places known via epidemiology studies to have a very low risk of recurrence or metastases, will have had that single tumour excised with good margins (R0).  The vast majority of people in these scenarios will go on to have normal lives. At the very least, they will classify in the full remission category. 

Immunotherapy will eventually cure cancer, right?

Immunotherapy is forecast to play a huge part in cancer treatment in the future, that we know. But to suggest that it’s a cure is overstating its current performance. Neuroendocrine Cancer has not been forgotten – you can read more about Neuroendocrine Cancer and Immunotherapy here.

I heard the Oncolytic Virus at Uppsala is a cure for NETs?

There is currently no scientific evidence that the Oncolytic Virus (AdVince) for any other oncolytic virus initiatives can cure humans with NENs. So far it has only been proven in destroying NETs in mice. The Oncolytic Viruses developed in Uppsala are now being evaluated in phase I clinical trials for neuroendocrine cancer. If you’re not up to speed with Oncolytic Virus trials, read more here – Oncolytic Virus

Isn’t prevention better than a cure?

This old adage is still relevant BUT the latest thinking would indicate it is not applicable to all cancers. Scientists claim that 66% of cancer is simply a form of ‘bad luck’ and if the claim is accurate, it follows that many cancers are simply inevitable. The thinking suggests that random errors occurring during DNA replication in normal stem cells are a major contributing factor in cancer development confirming that “bad luck” explains a far greater number of cancers than do hereditary and environmental factors. This scientific thinking is a tad controversial so it’s worth remembering that even if, as this study suggests, most individual cancer mutations are due to random chance, the researchers also admit that the cancers they cause may still be preventable. It’s complex!

The newspapers are always talking about breakthroughs and cures for cancer?

Newspapers looking for good headlines will use words such as ‘cure’. Sadly, headlines are generally written by sub-editors who scan the article and look to find a ‘reader-oriented angle’ for the heading. They either can’t or don’t have time to understand what’s actually being said. Unfortunately, this then leads to people sharing what is now a misleading article without a thought about the impact on those who are worried about the fact they have cancer and whether it can be cured or not.

Alternative Therapy cures cancer, right? There’s also a lot of fake health news out there – check out my article series about the problems with the internet and ‘Miracle Cures’. Cancer kills but so can fake cancer cures.

To cure, they must know the cause?

To a certain extent, that’s very accurate and the above paragraphs suggest how scientists look for causes. Have you ever wondered what caused your NET? I pondered this question in an article here. The only real known cause of NETs is currently the proportion of patients with heredity syndromes – see my article of Genetics and Neuroendocrine Cancer. Interestingly, the NET Research Foundation recently awarded funding to look at the causes of Small Intestine (SI) NETs (one of the most common types). A scientific collaboration between UCL, Dana-Farber Cancer Institute, UCSF Medical Centre and the UCL Cancer Institute / Royal Free Hospital London. The team’s approach has the potential to identify inherited, somatic (non-inherited) genetic, epigenetic and infectious causes of SI-NETs. Research is questioning whether SI-NETs are caused by DNA changes in later life or by aberrant genes inherited at birth; environmental influences or infectious agents – or is it a combination of all these factors? Very exciting. Read more here.

What would a cure mean to those living with NENs?

This is something that has crossed my mind, even though I don’t believe it will happen in my lifetime. I guess it would be good to get rid of the known remnant tumors left behind from my treatment (and any micrometastases currently not detectable and if they actually exist). However, many NEN patients are living with the consequences of cancer and its treatment, including surgery, chemotherapy, biological therapy, somatostatin analogues, radionuclide therapy, liver-directed therapy, and others. Many of these effects would remain – let’s face it, a cure is not going to give me back bits of my small and large intestine, liver, and an army of lymph nodes. So, support for those living with NENs would need to remain despite a cure.

Summary

The emotional aspect of the word ‘cured’ seems to be an issue across many cancers and it’s certainly very controversial in NEN circles. The world has still not cured the many cancers that exist. But over the next five to ten years the era of personalised medicine could see enormous progress in making cancer survivable. I think both doctors and patients need to take a pragmatic view on the ‘cured’ word and to end this article I wanted to share an interesting quote I found whilst researching. A controversial statement but I found it a pragmatic way to think about living with advanced and incurable (but treatable) Neuroendocrine Neoplasms