Once the diagnosis of cancer is made, cell type and the patient’s condition (as discussed in Part 2 on lung cancer) will determine treatment. Remember that all lung cancers are identified as either small cell carcinoma (with staging) or non-small cell lung cancer (NSCLC) with staging.
Now with the latest advancements in treatment known as “target-directed therapy,” the biopsy tissue is examined in depth, undergoing even more intensive classification of the NSCLC tumors. This approach led to the World Health Organization's (WHO) 2015 new classification of lung cancer, based on histology and not extent and spread, which the TNM system (tumor, node, metastases) used.
Special stains are introduced to the biopsy that further help to differentiate the cell types. These special stains are also useful in distinguishing when the tumor is “a primary mass from the lung” or if it is due to metastases from a bladder, breast, colon, kidney, or prostate cancer, among others.
In the past, squamous cell cancer was the most common type of non-small cell lung cancer. Now, it’s been outpaced by adenocarcinoma, which accounts for approximately one half of all lung cancer cases.
There are several theories for this. One is that the type of cigarettes available changed with time along with smoking patterns. The new cigarettes have filters and low tar so smokers tend to finish the cigarette, unlike previously when only half or two thirds of the cigarette was smoked. As you smoke the cigarette close to the filter, different carcinogens that accumulate (nitrosoamines), and they’re linked to adenocarcinoma risk.
In addition, there are many environmental and food sourced nitrosamines (e.g., charred meat) that may influence the prevalence of adenocarcinoma. Expect to hear more about these carcinogens as vaping and smokeless cigarettes become even more popular.
Adenocarcinoma tissue (obtained from a biopsy) is further tested for mutations in:
Epidermal growth factor receptor (EGFR), which is more common in women with no smoking history. These patients can be treated with the biological agents Erlotinib (Tarceva) and Gefitinib (Iressa).
EML4-Alk translocation is an abnormal configuration of the DNA, where two genes fuse, and the abnormal protein that is produced promotes uncontrolled growth of cells. These patients are treated with a biological agent called Crizotinib (Xalkori) that has been known to achieve 60 percent response rate.
KRAS mutation (discussed in Part 1 on lung cancer) is an oncogene that promotes uncontrolled growth of cells, leading to a genetic risk of lung cancer. It occurs in approximately 25 percent of all patients with NSCLC. Selinexor is currently recommended for treatment, though the efficacy is still not fully known and more research is needed.
Other features of the adenocarcinoma can be identified to help predict behavior of the tumor and prognosis, as well.
The good news is that all these variables help to direct individualized treatment for every patient, rather than having one protocol for all adenocarcinoma lung patients, as in the past.
Another change is the help that the new classification provides. Previously there was a type of cancer, bronchoalveolar cell carcinoma, which was often confused with a pneumonia diagnosis on standard chest x-rays. Delayed diagnosis often occurred. It is now identified as adenocarcinoma in situ, and treated and staged the same way as other adenocarcinomas, with an excellent prognosis.
Squamous cell lung cancer is the second most common kind of non-small cell lung cancer. It arises in the inner portion of the lung, which makes it more difficult to resect. It is more strongly associated with smokers and comprises 20-30 percent of the NSCLC. It is associated with 40,000 - 50,000 deaths per year in the U.S. In contrast to adenocarcinoma, advancements in treatment have been slow to identify biologic agents.
Large cell lung cancer is the rarest form of NSCLC. It is often made as a diagnosis of exclusion and not infrequently referred as “non-small cell lung cancer not otherwise classified” (NSCLS-NOS) as suggested by the WHO classification. It usually grows in the periphery of the lung and is often amenable to surgery.
Small cell lung cancer comprises 15 percent of all the cancers and is rarely found in non-smokers. Its name reflects the size of the cells that are similar in size to blood lymphocytes with the nucleus taking up most of the cell. These cancer cells are extremely fragile, breaking easily and leading to high rate of spread. That’s why resection is not recommended for this type of cancer.
Newer biological agents, PD-1 inhibitors, have been developed for small cell cancer. The mechanism of these drugs (programmed death) is to help prevent lymphocytes from exhaustion as they fight off the tumors. The lymphocytes can then be far more effective battling and destroying the cancer cells. These PD-1 inhibitors include Nivolumab (Opdivo) and Pembrolizumab (Keytruda).
Neuroendocrine tumors have the ability to secrete hormones that act on distant sites causing changes in the body’s natural steroids, sodium and calcium levels, among other functions. They comprise groups from the small cell, large cell and a non-malignant type of tumor called carcinoid. Despite being “different cancers,” these all share a similar origin, arising from remnants of embryonal cells. In this case, changes in the above mentioned levels may actually point to diagnosis of this type of lung cancer tumor.
The goal in treatment of lung cancer continues to focus on finding more targeted therapies with fewer side effects.