It’s not uncommon for patients to ask me how long a malignant illness has been living their bodies and how fast it will continue to develop. Why haven’t they felt anything? Why were the test results normal? They haven’t missed any appointments with their doctor, but the diagnosis is negative – cancer!
At any given moment, the number of cells, in the dividing or multiplying phase, in both tumour cells and normal tissue is quite small. If that wasn’t the case, then the speed at which cells grow would be phenomenally fast and the number of cells would soon reach astronomical proportions. Thankfully, this process is limited also in malignant tumours.
Here it would be appropriate to explain how growth differs in benign and malignant tumours.
Benign tumours develop from healthy cells and they usually grow slowly – over months, perhaps even years. Benign tumours never infiltrate neighbouring tissues. Benign tumours can occasionally reach impressive sizes, pushing or squeezing other organs, but they never spread into those organs. These tumours can be painful, uncomfortable, can be seen with the naked eye and can often be felt or even cause a cosmetic defect. Benign tumours can also cause significant health problems, especially if they develop in, for example, the brain. Benign tumours are usually contained within a fibrous capsule, so they have clear borders that are tangible (smooth contoured formations that are clearly separate from surrounding tissues) or visible in an ultrasound, X-ray examination, CT scan or an MRI. Benign tumours occasionally secrete hormones or other biologically active substances, which can affect various functions of the body. Benign tumours never metastasise in lymph nodes or in other distant tissues or organs. For this reason they’re not fatal, but, due to their location or size, can cause significant complaints and symptoms. After they’ve been surgically removed, they usually don’t return, unless, in rare cases, the tumour wasn’t completely removed.
Malignant tumours develop from cancer cells and they usually grow faster. However, there are certain tumours that grow slowly and it’s even possible that a person can die from a completely different cause with a tumour firmly lodged inside them. This can happen with tumours of the prostate and a large number of other cancerous pathogens (non-invasive formations that don’t grow in neighbouring tissue and have pronounced cellular atypia, or similarity to a malignant tumour). However, it would be wrong to put one’s faith in this possibility, because we can never know the exact moment when this situation can change. Malignant tumours grow directly into neighbouring tissues, literally drilling through them destroying natural borders and spreading via the path of least resistance. In addition, malignant tumours have a unique characteristic – their cells have the ability to separate themselves from their respective groups and spread throughout the lymphatic or circulatory systems, as well as simply peeling away and spreading to various natural cavities. In this way, for example, tumours often grow through the walls of the stomach or intestines where they can float freely in the abdominal cavity. After surgery, there’s always a risk that the tumour can return over time. Then we’re talking about a relapse or a metastasis. Even after destroying 99.99% of all cancer cells, over time the remaining 0.01% is enough to begin, under the right circumstances, multiplying and spreading once again.
Volume doubling time is the time it takes for the mass of the tumour to double in size. However, this time can vary between different types of tumours. Calculations derived from retrospective studies of patients with lung cancer tumours revealed that the volume doubling time was on average 223 days for fast-growing tumours and 545 for slow-growing tumours. Furthermore, the average number of days was 303 for adenocarcinomas, 77 for squamous cell carcinomas and only 70 for small cell lung cancer. The prognosis was better for those patients whose volume doubling times were over 200 days. It’s been estimated that for a tumour to grow to a mass of 1 cm3, an average of 30 volume doubling times are necessary or 30 full growth periods between two successful mitoses (the process of cell division). So if the volume doubling time is around 75 days, then 30 doubling times will take longer than 6 years. That means that even fast-growing tumours require several years to reach sizes that can be detected by medical diagnostic imaging methods. It’s been determined that the average volume doubling time for acute leukaemia is roughly 2 weeks, 3 months for breast cancer and 6 – 12 months for myeloma. By comparison, the average doubling time for the normal mucous membrane cells of the rectum is 24 hours. It has also been determined that after 39 – 42 episodes of doubling, the size of the tumour is so large that it is lethal to the patient.
This is why the notion of an early diagnosis can be misleading, because the tumour has already been in the host body for at least 5 – 10 years. This is also the reason why it’s not always possible to successfully treat all early stage cancers and to reduce their mortality rate. Biologically speaking, the term early essentially means late. This is why not all small tumours are considered to be early stage cancers, especially since they have lived half of their biological lives inside a person’s body. This is also the reason why mammogram screenings haven’t reduced mortality rates as much as was originally hoped. However, they can significantly reduce the spread of the tumour and prolong life. Screening results for cervical and intestinal cancers are different, as they often search for precancerous pathogens (conditions such as cervical dysplasia, colon polyps or adenomas, which, if left untreated, can lead to cancer). By surgically removing them or treating them in some other manner, the patient is spared from their potential transformation into cancerous tumours. Mammograms, on the other hand, essentially attempt to detect what we can call small cancers, because we still haven’t identified this organ’s precancerous conditions.
With today’s available detection methods, not all tumours that have been identified in their early-stages can have a positive prognosis, because it’s possible that dissemination, or the spread of the tumour cells throughout the body, has already occurred. The introduction of routine PET/CT (positron emission tomography) scans in oncology only proves this assertion as patients with tumours that were supposedly caught in their early stages have, unfortunately, already spread to other parts of the body, requiring a change in their treatment plans. If it was possible to detect tumours when they are only 2 mm2 (roughly 107 cells), instead of at the current size of 1 cm2 (roughly 109 cells), this would extend the patient’s monitoring period by about 3 years. These people would then be able to live for an extra 3 years as cancer patients, instead of just average citizens. In medical statistics this period is called the lead time bias.
We know that tumours metastasise at roughly the same pace as the initial tumour. So, for example, if the primary tumour’s growth to a detectable size (1 cm3) occurred over the course of 10 years, then roughly the same period of time will be necessary until its metastasis is determined and, likewise, if the primary tumour developed over the course of 3 years, then we can expect the metastasis to develop over the next 3 years after the diagnosis. This is why so-called late metastases aren’t actually late, but rather metastases that have grown in accordance with the original tumour’s pace of growth. From a biological standpoint, the generally accepted five-year life expectancy for many slow-growing tumours (breast, prostate, kidney, intestinal, etc.) is completely false. The volume doubling time is a much more precise measurement for tumours. The life expectancy for an untreated patient with a tumour whose volume doubling time is 10 days can live for another 100 days (a little longer than 3 months), but if the volume doubling time is 200 days, then we can expect the patient to live at least another 2,000 days or roughly 6 years. Tumours with very fast volume doubling times include testicular tumours, many paediatric tumours and some mesenchymal stem cell tumours (a variety of sarcomas). In such cases, the process occurs quite quickly, which is why it’s important to begin aggressive therapy as quickly as possible to reduce the mass of the cancer cells. But even this is no guarantee that effective treatment is possible for all cases.
The mass of tumour cells depends on the balance between the formation of new cells and the loss of existing cells (surgery, radiation, drug therapy). We can hope that therapy will significantly reduce the number of detectable tumour cells, but even if only a small amount of cells remain intact and they become active over time, the cancer can begin to spread once again and this time we won’t know its volume doubling time or how quickly the disease will advance. This is one reason why scientists have such high hopes for immunotherapy – to awaken and stimulate dormant immunity, so it can take appropriate action when a new clone army of cancer cells is born inside the body.