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Doctors, researchers re-thinking metastatic cancer treatments

Metastasis
Metastatic cancer accounts for up to 90 percent of all cancer deaths in the United States each year.

For all the advances made in cancer treatment over the past several decades, one statistic has remained unchanged: Metastatic cancer accounts for up to 90 percent of all cancer deaths in the United States each year.

That sober fact has motivated doctors and researchers to find new ways to treat metastatic cancer, which occurs when cancer spreads beyond its point of origin. Chemotherapy has been the standard treatment for many cancer metastases, while immunotherapy and targeted therapy have become relatively new options.

Today, some researchers continue to seek a better way to treat metastatic cancer, by focusing less on where a cancer originates or spreads and more on the extent of the spread. The working hypothesis is that the more limited the spread, the better positioned the metastatic tumors are to be removed surgically—or killed off through radiation therapy—and significantly increase the patient’s life expectancy.

The main course of action for widespread metastatic cancer involves flooding the zone with potential cancer killers such as chemotherapy drugs. Even in the cases of more limited metastatic cancers, doctors may still opt for such systemic treatments, concerned that diagnostic tests may not be catching all the cancer cells present. Doctors also have to weigh the benefit of procedures like surgical removal of metastatic tumors against potential negative outcomes of surgery. And then there’s the concern that, even if successful, the treatment may have little impact on the metastatic disease’s progression.

“If the cancer got there through some logical pathway that would suggest that that’s their only cancer, and you resect it or radiate it completely, you have a reasonable chance of them living a much longer period of time,” says Julian C. Schink, MD, Chief Medical Officer at Cancer Treatment Centers of America® (CTCA).

“The challenge is it requires a fair bit of judgment,” Dr. Schink says. Factors to consider include the length of time between the primary cancer diagnosis and the detection of a metastasis, if it develops in an area where the pattern of spread seems to have “the chance of being limited and controlled,” and what other treatments are available to the patient, he says.

“We talk about our strategies for eliminating that cancer, what are our best tools, and go from there,” Dr. Schink says. “We balance the treatment against the side effects of that treatment.”

What is metastatic cancer?

Patients new to a metastatic cancer diagnosis may be confused by the way their oncologists describe it. For instance, if testing uncovers tumors in your brain, why isn’t it called brain cancer?

Here’s one way to explain it: Imagine you’re a New Yorker from Brooklyn who retires to Boca Raton. You moved to Florida, but that doesn’t make you a native Floridian. You’re a New Yorker who now calls Florida home. It’s similar with cancer. It’s not where the cancer is situated, but where it originated that’s important. When breast cancer spreads to the brain, doctors refer to it as metastatic breast cancer to the brain, recurrent breast cancer in the brain or breast cancer with brain metastasis.

How did the cancer get there? Well, just like New Yorkers who may drive, fly or take a train to Florida, cancers have several ways to move around the body. Cells from the original tumor are constantly shedding. Some of these cells may evade the immune system and hitch a ride via the bloodstream or lymphatic system and travel to distant parts of the body.

Metastatic cancer’s travel is often predictable. Just like you’re more apt to find a retired New Yorker living in Florida than in Oklahoma—or a California retiree in Arizona than in North Dakota—metastatic cancers also tend to travel to specific areas Some of the most common cancers to spread, and their typical  destinations of metastasize, include:

Oncologists also have three ways of defining metastatic cancers based on their relationship to the original tumor site:

  • Locally advanced cancer is cancer that has spread to nearby tissues or lymph nodes.
  • Regional metastasis is cancer that has massed and concentrated in nearby body parts.
  • Distant metastasis is cancer that has traveled further to distant organs.

Treating metastatic cancer

“Nowadays, we have four different tools that we can attack cancer with, in my mind: surgery, radiation, chemotherapy and immuno-oncology drugs,” which include targeted therapy and immunotherapy, Dr. Schink says. “We have localized treatments, which are surgery or radiation; we have regional treatments, which are radiation; and then we have systemic treatments, which are chemotherapy and immuno-oncology.”

Localized treatments, when applicable, usually have the more promising outcomes for attacking cancer, Dr. Schink says.

But when it comes to metastatic cancer, chemotherapy has been the go-to approach for decades, inundating the body with chemical toxins to kill the cancer cells wherever they may be hiding—and, in the process, killing off many healthy cells, too.

“Sadly, most cancers cannot be killed in their entirety with chemotherapy,” Dr. Schink says. “Most cancers develop resistance to chemotherapy.”

In more recent years, oncologists have added targeted therapy and immunotherapy to treatment regimens for some metastatic cancers. Targeted therapy drugs identify specific molecules found on cancer cells’ receptors or proteins, with the goal of attacking or interfering with genetic features that allow the tumors’ cells to grow and divide. Immunotherapy stimulates the body’s immune system to recognize cancer cells as foreign bodies and attack them.

In many cases, doctors continue to follow today’s systemic treatment protocols because, despite advancements in technology, they can’t be certain that testing has pinpointed all the possible tumors or cancerous cells in a particular patient.

Localized treatment as an option

Some cancer research suggests that surgically removing metastatic tumors or killing them off with radiation may facilitate a better prognosis in patients with a limited number of identified tumors—say, five or fewer—a disease oncologists now describe as oligometastatic (oligo meaning “few” in Greek) cancer. The surgical removal of the tumors under this approach may also be combined with a systemic treatment such as chemotherapy.

The idea of using localized treatment in cases of limited cancer spread comes from a 25-year-old concept proposed by University of Chicago Drs. Ralph Weichselbaum and Samuel Hellman that’s gaining renewed interest today, according to an October National Cancer Institute (NCI) report. Back then, Drs. Weichselbaum and Hellman were refuting conventional wisdom that supported systemic treatments as the routine approach because many medical professionals felt that surgery subjected cancer patients to pointless treatment. The assumption then was that if metastatic cancer is found somewhere, chances are good that it’s everywhere. But Drs. Weichselbaum and Hellman asserted that if the cancer is not widespread, that local treatments such as surgery or radiation make sense.

Over the past five years, small clinical trials have tested the theory of using localized treatment for oligometastatic cancers, according to the NCI report. While researchers say the results are promising, other medical professionals caution that the studies haven’t proven that localized treatments will increase life expectancy or improve the quality of life for cancer patients. Some have found shortcomings that weaken the findings, the NCI report said. Larger, better-defined clinical trials are now underway.

Dr. Schink says he’s long been supportive of localized treatment of metastatic cancer where it makes sense. The chances of success are best, he adds, when the metastasis involves between one and five tumors—preferably three or fewer—and they show up several or more years after the original diagnosis.

“If it takes two, three, four years for that to show up, and it’s the only spot that shows up, you have a much better chance. You go after it, you treat it, there’s a much better chance that you’re going to control it for a long, long time, if not forever,” Dr. Schink says. “On the other hand, if something shows up three months after you finish your initial cancer therapy, chances are it isn’t really oligometastatic disease—it’s just the tip of the iceberg.”

Some research is exploring microRNAs, which regulate gene activity, searching for molecular patterns that “could identify patients whose cancer is less aggressive and could thus be good candidates for direct treatment of their metastatic tumors,” the NCI report said.

Treatment of colorectal metastasis offers hope

One area where localized treatment of metastatic cancer has become almost routine is colorectal cancer that has spread to a limited number of spots on the liver. The NCI report cites observational studies in the United States and Europe that found that about 20 percent of patients survived for at least 10 years after undergoing surgery to remove a primary tumor and the metastatic tumors on their liver. These studies weren’t clinical trials and didn’t include documentation of other treatments the patients may have received.

Still, those successes have made an impact on treating the spread of cancer. Dr. Schink recalls in 1994 treating a law professor whose ovarian clear-cell carcinoma had metastasized, developing new tumors on her liver. Chemotherapy was having no effect.

“She hands me this little newspaper clipping about treating colon cancer with liver metastases with surgical therapy. She goes, ‘Why aren’t we doing this?’ And I said, ‘It’s colon cancer’ it’s a different cancer,’” Dr. Schink says. “She goes, ‘Well, this isn’t working.’ I said, ‘No one’s ever done it before for ovarian cancer, at least not that I’m aware of.’ And she goes, ‘So? I’ve got nothing to lose.’”

That woman, 26 years after undergoing surgery to remove the metastatic tumors, continues to do well, Dr. Schink says.

‘Leaving no stone unturned’

Localized treatment options may also make sense for some sarcomas that aren’t sufficiently chemo-responsive. “If systemic therapy doesn’t work, it moves surgery or radiation up on the list,” Dr. Schink says. Metastatic cancers that may benefit from localized therapies include recurrent colon cancer, recurrent ovarian cancer, recurrent endometrial cancer and, sometimes, recurrent breast cancer.

“We are absolutely committed to not overtreating anyone, but we’re also equally committed to leaving no stone unturned when it comes to finding some way to help them if reasonably possible,” Dr. Schink adds.

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