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Local Therapy for Metastatic Disease: Why Might We Break the Rules?
Tue, 09/07/2010 - 17:45
H. Jack West, MD, Founder, President and CEO

One of the most common questions. we receive is why people are told that surgery isn't an appropriate option for metastatic disease. If you can see the areas where there is active cancer, why can't you just take it out?

The problem is that it's very rare for a metastatic cancer to be limited to the areas that we can see. If a cancer spread from the lung to the liver, adrenal gland, brain, bones, or the other lung, it got there by having microscopic cancer cells (micrometastases) travel through the bloodstream to get there. Because this almost always means that there are many other micrometastases in the bloodstream, we're fighting not just the cancer we can see, but the potential future areas of cancer we can't see because they're in the bloodstream, with the ability to settle in new places and grow into new lesions. So the general treatment strategy is systemic (whole body) treatment that travels through the bloodstream to reach cancer cells that may be distributed throughout the body.

In contrast, surgery or radiation are strategies for treating a single area of disease very effectively. If you're confident that the disease is limited to one focus or general area, either is more reliable than chemo at eradicating disease in a focal area. Surgery tends to have more morbidity, though it's the most definitive way to treat localized disease. Radiation can still do a good job at treating the local area, and it's often well tolerated enough that it's commonly integrated into treating metastatic disease under certain circumstances.

The most common settings in which local treatment is recommended are things like brain metastases, hemoptysis (coughing up blood), painful bone lesions, or compression of an airway. Though surgery is sometimes used for 1-2 isolated brain lesions, these days more and more of these localized/local problems are treated with radiation, because of its admirable combination of efficacy and good tolerability.

What these situations share is a common theme of the local problem being a more pressing issue (literally or figuratively) than the systemic disease. Brain lesions can cause local swelling and neurologic symptoms, and you can get in big trouble in a short time if brain lesions aren't controlled, because there isn't extra real estate for swelling inside the skull. Similarly, compression of an airway is a major problem even if it's concentrated in a limited area.

In most cases of metastatic disease, the problem isn't so much one spot causing a crisis. If someone has two liver metastases and another in an adrenal gland, you can take them out, but it's likely that someone will be set back or even quite debilitated by the surgery, only to have a few new metastases appear before a person has recovered enough to consider chemo or get back to enjoying their life. That's because for most metastatic cancers, the threat is more of a global/whole body threat than a specific focus. Systemic therapies are the ideal treatment for a whole body threat -- they cast the widest net.

We've already covered the concept of the precocious metastasis, which is a person with a single metastasis, most typically to the brain or adrenal gland, when the rest of the cancer appears to be earlier stage, and which can be associated with very long survival that is debatably even cured. The real debate about this is whether the people who do well for years after surgery for a solitary brain metastasis do well because of the surgery or because they had a rare version of lung cancer that presented with a solitary metastasis, which predicts that even if it progresses, it might do it in a very indolent way. In other words, perhaps these people would do as well no matter what they do.

A variant on this theme is that sometimes a person will have multiple areas of cancer visible, but only a single area is progressing at a rate that is clinically meaningful. I've most typically seen this in a person with adenocarcinoma/bronchioloalveolar carcinoma (BAC), in which they have a bunch of background nodules that appear to be barely changing over a series of scans, while one area is more solid appearing and is growing more significantly. Or sometimes it's a person who is referred to a surgeon for a growing nodule but who also has one or a few really tiny nodules in the background that are just too small to characterize -- perhaps they can't be biopsied because they're only 2-3 mm. Sometimes you'll have done a few scans on a person and see that one lesion that has now been biopsy-proven to be an adenocarcinoma, while the other background nodules make you concerned, but they aren't changing between the scans you've gotten.

These are situations in which I think it's very appropriate to pursue local treatment. If it's someone being referred to a surgeon for one growing biopsy-proven cancer and a couple of tiny, ambiguous nodules, I might favor repeating a scan at least 6 weeks from the first one to see that these aren't all going to be growing before someone's recovered from surgery. But if someone's seeing a surgeon for a nodule that grew after 3-6 months of follow-up scans, while everything else is stable, I'm all for doing the surgery and taking our chances with the ambiguous nodules in the background.

Sometimes it's in the setting of known metastatic disease, but the principle is basically that you have a local issue outpacing the background. If I have a patient in whom I'm seeing that one area is growing far faster than everything else, I might occasionally refer a person for local treatment and taking chances with the background. If you follow baseball, this is essentially the concept of getting out the lead runner. This concept is certainly more appealing for people with the most isolated lesions growing while everything else has been followed for long enough to be confident that there isn't going to be widespread progression on the next scan. So it's not something I try to rush into if someone has one favorable scan with a residual visible lesion after many were present 6 weeks earlier. I'd like to have some confidence about the trajectory of a person's disease first.

Importantly, this isn't a standard treatment approach that is recommended in any textbook, but rather is an approach that I consider a reasonable option in very individualized cases, based on a good rationale. Partly because of the fact that this isn't a clearly evidence-based guideline, I typically favor radiation in such settings because it can still be an effective way to eradicate a local lesion, but it doesn't tend to entail the same morbidity as a surgery that would be pushing the envelope.

I'd venture to say that different oncologists have different philosophies about how and when to deviate from the general rules. It's part of how medicine is individualized. But it's worth knowing that while I consider metastatic disease to usually NOT be appropriate for surgery or routine use of radiation to eradicate all visible disease, I think it's important to not fall into this being dogma.

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