Diagnosing and treating lung cancer requires far more than measuring the size of cancer cells under a microscope. But those sizes are a critical first step in understanding the distinction, scope and extent of the disease and its treatment options. That’s because, even today, lung cancers are generally divided into two categories: small cell (SCLC) and non-small cell (NSCLC), named when pathologists first differentiated lung cancers by the size of the affected cells. “The traditional diagnosis was based on pure pathology,” says Dr. Shayma Kazmi, a Hematologist-Oncologist and Medical Oncologist at our hospital in Philadelphia. “They found that the cancer cells were either small cells, or they were larger cells, such as adenocarcinomas or squamous cells. And so they simply got grouped into those separate categories, small cell or non-small cell cancer.”
types of cancer
Now that scientists know more about the two types of cancer, they understand that they don’t just look different; they behave differently, too. One significant difference is their rate of growth. SCLC is often very aggressive and grows quickly, due, in part, to the presence of a protein known as Ki-67. This protein is found in many cells and is thought to drive cell proliferation. It may also be found in tumor cells in lung, prostate and breast cancers. “Some of the non-small cell cancers may be found to have a moderate percentage of Ki-67,” Dr. Kazmi says. “But small cell cancers may have a very large percentage of Ki-67, making them among the fastest growing solid tumors.” Most small cell lung cancers are the oat-cell variety—named because the cells often resemble oat grains—but some may be considered combined small cell, which may also include some larger cells.
Prolific cancer cells
Prolific cancer cells, such as those found in SCLC, often react quickly to treatments such as chemotherapy, but they may also bounce back aggressively and become more resistant to treatments. “When you treat them, sometimes they melt away very quickly,” Dr. Kazmi says. “The faster growing the cells, the quicker they also die. So they can have a very quick response to chemotherapy. But they also come back raging, which is the hallmark of a small cell cancer.” Radiation and surgery may also be recommended to treat small cell lung cancer.
There are three main types of non-small cell lung cancer:
- Adenocarcinoma, usually found in the outer reaches of the lung, accounts for about 50 percent of all non-small cell lung cancers.
- Squamous cell carcinoma, most often found in the central or inner parts of the lung and/or along the trachea, accounts for about 30 percent of all non-small cell lung cancers.
- Large-cell undifferentiated carcinoma, which can be found anywhere in the lungs, accounts for up to 15 percent of all cases.
NSCLC is much more common than SCLC and accounts for nearly 90 percent of all lung cancer cases. SCLC accounts for less than 10 percent of all lung cancer cases. And NSCLC has a higher survival rate. According to the American Cancer Society, the survival rate at five years for someone diagnosed with stage I SCLC is about 31 percent. The survival rate at five years for someone diagnosed with stage I NSCLC is nearly 50 percent. While tobacco smoking remains a leading risk factor for all lung cancers, the small cell variety is very rare in non-smokers.
Another difference, even among lung cancers in the same SCLC or NSCLC category, is how they are treated. “It really matters if someone has an adenocarcinoma or a squamous-cell carcinoma because there are different treatments.” Dr. Kazmi says. “So they all should not be lumped into the non-small cell lung cancer category.” NSCLC patients typically have more treatment options than those with SCLC. Targeted therapy drugs such as crizotinib (Xalkori®), erlotinib (Tarceva®) or bevacizumab (Avastin®) may be recommended for some NSCLC patients. Immunotherapy drugs known as checkpoint inhibitors, such as pembrolizumab (Keytruda®) and nivolumab (Opdivo®), have also been approved to treat non-small cell lung cancer.
What’s the difference
The language of cancer can be a confusing mix of unpronounceable words, sound-alike terms and scientific jargon. But some of the nuances in cancer types, terms and titles may indicate deep differences in the diseases, diagnoses and treatments. This blog is an installment in an occasional series called “What’s the difference?” designed to help clear up some of the confusion in cancer vocabulary and help increase our cancer IQ.