For a long time, survival in lung cancer patients has remained poor, and hence both lung specialists and the cancer specialists have carried a pessimistic attitude toward it. However, this is rapidly changing. Survival has more than doubled, and side effects of cancer therapy have reduced significantly in recent years by virtue of the discovery of the how the mutations and immune system play a role in lung cancer, with development of targeted therapy and immunotherapy against them. The section below provides the magnitude of the various aspects of lung cancer such as how many cases in a year, gender differences, and survival in lung cancer as it stands today, in the form of four questions, and their answers.
Statistics of Lung Cancer
Lung cancer kills more people than four most common cancers (breast, colon, pancreas & prostate) combined. Approximately 1500 people are diagnosed with lung cancer every year in Singapore. Adenocarcinoma is the most common sub-type affecting 43.5% of patients with lung cancer. Women are affected more frequently (43%) with adenocarcinoma than men (21%), and the age of onset of adenocarcinoma can be as early as 31 years.
Approximately 32% of all lung cancer patients, and 55% of patients with adenocarcinoma sub-type are non-smokers dispelling the notion that only smokers are at risk. Right and left upper lobes, are the most affected sites confusing physicians into misdiagnosing cancer as Tuberculosis. 82% of patients present with cancer close to the large airways (wind pipes) in the form of lymph node. 32% of patients with adenocarcinoma carry activating epidermal growth factor receptor (EGFR) mutation. Most patients, 68% present in advanced stage, and median survival in advanced lung cancer is only 122 days.
Question # 1: Is It Lung Cancer?
Chest radiograph can only pick up early stage cancer if it is greater than 1 centimetre in size. Anything smaller and hence curable, is missed by chest radiograph indicating its limitation to diagnose most gainful (by virtue of their early stage and potential cure with operation) group of lung cancer patients. Computed tomography (CT scan) is needed in each and every patient to guide the how the biopsy should be done to obtain a sample of the abnormal area in the lung.
On CT scan, lung cancer expresses itself in five patterns. A white spot at the close to the outer edge of the lung, a lymph node in the centre of the chest, distortion of the parts in the centre of the chest, cancer blocking the wind pipe, and accumulation of fluid within the space between the outer lining of the lung and the chest wall (pleural effusion).
In order to confirm diagnosis of cancer, a sample form the abnormal area is needed. This is best obtained by passing a needle into the lung from outside if the location of the suspected cancer is close to the outer surface of the lung. If the suspected cancer is located toward the centre of the chest or lungs, bronchoscopy with ultrasound (EBUS-TBNA) is the preferred method.
In case of the fluid accumulation within the space between the lining of the lung and chest wall, a technique similar to the water tap in our houses called pleural tap is used to collect and drain the fluid which is then sent for testing for cancer. Sometimes extraction of a small piece of the lining of the lung is also done. The technique of passing needle into the lungs from outside carries the risk of puncturing the lung (pneumothorax) in 24-40% of patients.
The chances of picking up the cancer with this technique depends on the size of the suspected cancer but is close to 90%. The risk of accidentally puncturing the lungs with bronchoscopy with the ultrasound is almost nil and the chances of picking up cancer close to 80%. The chances of picking up cancer with pleural tap of the fluid accumulated within the space between the lining of the lung and the chest wall and biopsy of the lining of the lung is 50% and 98% respectively.
Question # 2: Can We Take It Out?
Since removal of the lung cancer by operation carries the highest chance of survival, this is the second most important question. This question is answered by identifying the stage of lung cancer. Cancer in stages I & II, and in some cases stage III (IIIA) can be removed by operation, whereas stage IIIB and IV cannot be removed.
These must be treated with chemotherapy, radiotherapy, targeted therapy, and immunotherapy either alone or in combination. Stage of the lung cancer is determined by two ways. Some physicians prefer to perform CT scan of the brain, CT scan of the abdomen and pelvis, and bone scan, whereas some physicians perform MRI scan of the brain, and PET scan for staging. MRI brain and PET scan is more accurate and preferred tests. If the answer to second question turns out to be “yes” after staging scans, the 3rd question needs to be asked and that is—
Question # 3: Should We Take It Out?
Some patients despite having early stage lung cancer are not physically fit to endure removal of a part of or whole lung, as many of them have underlying COPD from smoking. As a result, they have poor lung function to undergo operation. Doctors measure lung function by what is called FEV1 and DLCO for assessing the patient’s fitness for operation. FEV1 and DLCO of < 60% carry increased risk from operation.
In addition, some may have a weak heart from previous heart attack or other heart condition, or some may be too old to undergo or tolerate the operation. Such patients are identified by performing lung function test and if found not suitable, are treated with strong dose of radiation therapy. If the answer to the second question is “no,” then the next question needs to be asked, and that is—
Question # 4: Can Targeted Therapy or Immunotherapy Be Administered?
On average, the survival in “untreated” advanced lung cancer is 4-5 months, and 10% survive more than a year. Chemotherapy has been the main way of treatment for last four decades for patients with advanced lung cancer but response rates and survival have remained poor and largely unchanged from 13% in 1975 to 16% thirty years later in 2003. The survival in advanced lung cancer treated with such chemotherapy is 8-12 months, and 33% survive more than a year.
However, over the last decade, new insights into the development of lung cancer have been gained. When looked at a molecular level, lung cancer has been found to be of several types each driven by a different mutation. Identification of these activating mutations such as EGFR, ALK, ROS1 etc., have significantly changed the survival statistics of lung cancer. The resulting emergence of tablet therapy targeted at blocking the cancer path activated by these mutations (targeted therapy) has proven to be twice as effective as standard chemotherapy.
Survival in advanced lung cancer treated with targeted therapy is 22 months and ~53% survive more than a year. In addition, it carries minimal side effects (acne & diarrhoea) and the convenience of oral administration, in contrast to conventional chemotherapy, side effect profile of which is relatively more toxic, and which requires patients to come to hospital for receiving it.
Most therapeutic benefit has so far been seen in patients with “adenocarcinoma” type of lung cancer which nevertheless affects the majority of patients; however, striking success seen has provided impetus to gain similar benefits in squamous cell and small cell carcinoma sub-types of lung cancer as well. In addition to targeted therapy, immunotherapy based on using patient’s immune system to inhibit growth of cancer cells for lung cancer patients is emerging as yet another option for these patients and carries promising outcomes.
In conclusion, long standing pessimism surrounding lung cancer is fading. Better understanding of the molecular profile of lung cancer and role of immune system in driving it is making novel therapies available. It is hence necessary to stay tuned for both doctors and patients to benefit from these developments.