After several weeks of posts on other aspects of lung cancer, I am long overdue to write on small cell lung cancer (SCLC). Although it is good to see the number of SCLC cases decreasing over time, and becoming a smaller and smaller percentage of lung cancer cases overall (only about 13% in the US and steadily falling), this has translated into fewer clinical trials and less of a focus on SCLC in the lung cancer community. However, there are some promising developments that may lead to some long overdue progress in the field.

First, this post will start with some general concepts and an introduction to SCLC, and this will be followed in the next few weeks by posts describing current and emerging ideas for the basic stages of small cell lung cancer, and also a discussion of prophylactic cranial irradiation for small cell, where it has been most extensively studied.

SCLC is one of the two major types of lung cancer, and although it used to be taught as comprising 25% of lung cancer cases, in the last 15 years that has dropped to 20%, then 15%, and now below that. This is probably because it is the type of lung cancer most closely associated with smoking, often more than a pack per day for many years. It is so commonly associated with smoking that some experts say that if SCLC is diagnosed in a never-smoker, you need to re-examine the pathology or question the patient about smoking when his or her spouse (or child, or whoever) is outside of the room, just to confirm that they are really a non-smoker. It's fair to say that cases of SCLC in never-smokers are exceptionally rare.

SCLC develops in "neuroendocrine" cells toward the center of the chest. These can release hormones in the bloodstream, so SCLC is the kind of tumor most likely to be associated with "paraneoplastic syndromes", or problems indirectly from the cancer. It can cause strange neurologic syndromes by creating antibodies against nerve cells in the brain or connecting to muscles, and it can alter the salt balance in the body from proteins released by cancer cells. Although these can sometimes have special treatments to deal with those separate syndromes, treating the underlying cancer is one of the more effective ways to deal with these problems.

Most SCLC tends to grow quickly, developing bulky masses in the middle of the chest, can worsen over days or weeks at a time (NSCLC tends to grow more slowly). The most common symptoms are a cough, fatigue, decreased appetite, non-exertional chest pain (unlike angina, which is primarily chest pain associated with exertion), and coughing up blood, also known as hemoptysis (hee-MOP-ta-sis). It also has a great tendency to spread early, which is the main reason we don't routinely consider surgery for the treatment of SCLC. It has such a high risk of spreading that whole body treatment with chemotherapy is the cornerstone of treatment for all cases, both limited stage and extensive stage. 90% of cases have spread to lymph nodes in the middle of the chest, about 2/3 of cases have spread to distant organs, and about in some studies 70% of SCLC tumors to the brain within two years. The brain is VERY fertile soil for SCLC, which is the major reason brain radiation is so strongly considered even for patients who don't have evidence of cancer there on scans, as a prophylactic treatment.

While there is a more detailed staging system for SCLC, almost nobody uses one more complicated than a basic breakdown into two categories, known as limited stage vs. extensive stage. There is a little play in the exact definitions of what can be considered as limited or extensive even among experts. Basically, the definitions are functional, based on the limits of how much radiation you can safely give to a patient. If you can fit all of the SCLC into a radiation "port", or the target for treatment, it can be considered limited stage, vs. extensive disease if you can't. See figure:

(click to enlarge)

In truth, however, cancer that spread throughout the bloodstream to another area has the ability to travel to other parts of the body, so even if you had a cancer in the liver near a main lung lesion and could do radiation to everything you can see, you generally wouldn't because the liver spot got there by spreading through the bloodstream, so it's an extensive stage cancer. Overall, about 1/3 of SCLC is limited stage (or LD-SCLC), and the other 2/3 are extensive stage SCLC (or ED-SCLC). It is possible to cure LD-SCLC, although it's challenging and not as frequent as we would like. Despite our best efforts, it isn't possible to cure ED-SCLC.

As a rule, SCLC is very responsive to initial treatment, with chemotherapy or radiation or both. In fact, sometimes chemotherapy and/or radiation can kill tumor cells so quickly the kidneys can have a problem processing all of the breakdown products in those dying cells, a problem called tumor lysis syndrome. That's still uncommon. But you can see terrific improvements in SCLC within just days after starting treatment, so we consider the vast majority of patients, including older and frail patients, to be candidates for treatment for SCLC, because they can often dramatically improve with treatment.

I'll discuss the historical and emerging treatments for SCLC soon.