Exploring the paradigm shift in the treatment of lung cancer.
WORLDWIDE, lung cancer is the most common and deadly form of cancer; it accounts for 1.6 million new cancer cases annually.
Approximately 1.38 million people die from lung cancer, and it is a gargantuan myth that it is a smokers-only disease, confined to men.
Evidence reveals that more and more non-smokers are included in this morbid statistic. And women are more susceptible to developing lung cancer.
In Malaysia, more than 80% of women who developed adenocarcinoma (the most common lung cancer subtype) are never smokers.
There are no conclusive indications why this is so, but it is strongly suspected that genetics and environment play a large role.
The current prevalence of lung cancer in Malaysia is around 18 per 100,000 of the population. With almost 3,000 new patients diagnosed each year, there is a possibility that lung cancer is still on the rise.
Screening for lung cancer
According to Datuk Dr Mohamed Ibrahim Abdul Wahid, consultant clinical oncologist and president of the Malaysian Oncological Society and the Asian & Pacific Federation of Organisation for Cancer Research and Control, cancer cells can progress rapidly, even in the early stages. As such, early diagnosis is the key to treatment.
"Right now, there are no proper methods to screen for lung cancer. There are blood tests which test for lung cancer tumour markers, but these are primarily used as a guide for patients who have cancer; after giving treatment, if the markers go down, doctors knows that the treatment is working. But if it goes up instead, doctors will know that something has gone wrong," remarked Dr Ibrahim.
"One of the biggest problems with tumour markers is that they can give a lot of false positives, and can lead to unnecessary stress and worry."
He added: "It's not just the false positives that these test kits can generate, there are also a lot of false negatives; that is why they should never be used as a screening tool."
Similarly, genetic screening or genetic profiling is not a viable method of screening for lung cancer. What it does is show whether you are at risk, but this does not mean that you will develop lung cancer.
Early detection
Catching lung cancer in the early stages means a higher chance for doctors to save the patient. The biggest problem with lung cancer is that the only way to detect it is with CT or PET scans. There are low dose CT scan alternatives, but as a screening tool, it is not acceptable as it also exposes the patient to radiation, and it's not cheap.
"One of the ways of diagnosing lung cancer is to look at the history of the patient and examine the patient. This should be followed by a CT scan and bronchoscopy. If the tumour is in a deeper part of the lung, then doctors may need to do a CT-guided bronchoscopy.
"It is not enough to check from the CT scan, as a biopsy is needed to confirm the type of tumour, and also to find if it is primary or secondary cancer. Lung cancer means it originates from the lungs, but if the cancer is from other parts of the body and has spread to the lungs, then the doctor planning treatment will need to take this into account," explained Dr Ibrahim.
Under the radar
Consultant oncologist Dr Kevin Hew noted that lung cancer has a tendency to stay hidden until the very last minute.
"For many patients, the lack of symptoms is often why they do not realise that they have lung cancer, and by the time symptoms start appearing, the cancer is already in its advanced stages.
"Lung cancer is basically divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC consists of several other types, of which adenocarcinoma has the highest number of patients compared to other NSCLC types," he added.
Dr Hew opined that part of the reason is because of the improved filters used by cigarette companies.
"Smokers need to inhale more deeply in order to get the same 'kick', and this deeper inhalation leads to carcinogens in cigarette smoke being introduced into the deeper parts of the lungs.
"Previously, most lung cancers presented in the upper airways, which trigger coughing or breathing difficulties in patients who then get treatment earlier (earlier diagnosis of lung cancer). But with adenocarcinoma, it is usually diagnosed late because it is 'silent' in the earlier stages of the cancer," he explained.
Treatment in stages
For the earlier stages of cancer, the treatment of choice is often surgery. This option is usually open for patients with Stage 1, Stage 2 and Stage 3A cancer. Patients are not given other targeted therapy drugs in case of cancer recurrence; there is a possibility that the cancer may become immune to the effects of the drug, thus rendering it useless for future use with the same patient.
Of course, it is not as straightforward as simple surgery. Depending on the size and location of the tumour, some patients may need to undergo a few cycles of chemotherapy prior to surgery.
But when it comes to late stage cancer, whatever treatment given is not so much to cure the cancer, but more towards controlling it. This typically means that the treatment given is to delay progression.
The issue in treatment is: should they get standard chemotherapy and then immediately get targeted therapy? Should they get targeted therapy with chemotherapy?
Compared to targeted therapy, chemotherapy usually works on a broader spectrum. Where targeted therapy only addresses specific molecules in cancer cells, chemotherapy has a much broader approach; while it can be effective, it does tend to cause unwanted side-effects.
Since chemotherapy is designed to stop or slow the growth of cancer cells, it frequently damages healthy cells. This often leads to side effects like nausea, vomiting, and hair loss.
These side effects are usually not permanent and your body can recover once the chemotherapy is stopped.
Because of the physically demanding aspect of chemotherapy, it cannot be given continuously over a long period of time. At best, it is given for around seven to eight cycles, as it will affect the patient's bone marrow (which takes a long time to recover).
Of course, this is not to say that standard chemotherapy is being phased out. Instead, it is also evolving with time. In the past, the use of a one-size-fits-all approach was the only available means to fight cancer. Sadly, this was highly inefficient, but many improvements have been made through the years.
Targeted therapy
Things are beginning to change for the better; targeted therapy is slowly changing the way cancers are treated. In lung cancer, it gives patients with advanced Stage 3B and Stage 4 NSCLC a chance of a better quality of life.
This methodology relies on new breakthroughs in the understanding of cell biology at the genetic and molecular level.
Cancer cells radically alter the signalling networks of normal cells that regulate cellular activities controlling cell division and survival. Targeted therapy represents a means to interrupt this signalling network.
It is becoming the choice for first-line treatment as it is highly effective and have minimal side effects.
This is crucial, especially for the treatment of advanced Stage 3B and Stage 4 NSCLC, where patients are often not capable of enduring the stress placed on their bodies by chemotherapy.
"The discovery of the EGFR mutation was of great import. When the class of oral drugs known as EGFR-TKI was used four years ago in EGFR mutation positive patients, the results were very encouraging," Dr Hew said.
"The advantage of using EGFR-TKIs is that it is effective, with manageable side effects. The patient can endure long term usage of the drug. This effectively converts lung cancer from a disease with a very short life span into a chronic illness where the patient lives with the disease for a longer period of time.
"For patients who develop lung cancer because of EGFR mutation, the effective method of treatment is the use of EGFR-TKIs to block or inhibit the signals used by the cancer cells; this deprives the cancer cells of their means of proliferation, thus causing it to die off. These drugs are mainly used for advanced stages of NSCLC (Stage 3B or Stage 4).
"It is important to note that in the advanced stages of lung cancer, any treatment options that are available are meant to manage or control the cancer, and not cure it," stressed Dr Hew.
Dr Ibrahim was quick to stress that targeted therapy is not recommended for use in the earlier stages of cancer. This is due to the possibility of the cancer recurring, and if this happens, there is the possibility that the cancer may develop immunity towards the drugs used against it during the earlier stage.
"Patients with EGFR mutation positive Stage 3B and Stage 4 NSCLC who are in the advanced and inoperable stages could have the choice of selecting targeted therapy as first-line treatment. Currently, this option is only available for patients who are EGFR mutation positive."
The beauty of this treatment is that it allows lung cancer patients to sustain a reasonably good quality of life throughout the time that they are receiving the drug as they do not need to suffer the rigours of chemotherapy.
"At this point, looking at averages, we have moved the survival rate from three months to around one year. This means that while there are patients who only survive a few months, there are also some who survive for a few years. It is currently still beyond the capability of modern medicine to cure. The best that can be done is to control the cancer or its symptoms and improve the quality of life for the patient," shared Dr Ibrahim.
Like many targeted therapies, EGFR-TKIs come at a price. But it is worth noting that this oral treatment brings hope to advanced NSCLC patients. Survival rates have improved, and equally important, the quality of life for patients has also improved.
Both Dr Ibrahim and Dr Hew noted that this is a fantastic development, and sees this as a delivery on the promise of targeted therapy and advanced medicine.
"Most patients with EGFR mutation who received EGFR-TKIs have had some benefit. It is effective in controlling the cancer from progression. By testing for EGFR mutation, doctors will be able to make a more informed treatment choice for the patients.
"Conversely, if a patient is EGFR mutation negative, then EGFR-TKIs are not likely to demonstrate any efficacy. This spares the patients from wasting time and resources for taking a drug that is not going to help them."
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