The Role of Surgery in Metastatic Cancer
If a stage IV cancer forms metastases in several regions of the body, then surgery will play a limited role because surgeons cannot remove large portions of the lungs, brain, and bones in an effort to eradicate tumors in these locations. The focus is, by necessity, on treatments that attack the cancer throughout the body-namely, drugs.
Yet surgery can play a pivotal role leading to the long-term survival of some individuals with stage IV cancer. Some cancers form metastases that are confined to one organ, called “isolated metastases.” This situation may be encountered at diagnosis or when a cancer relapses sometime after its initial treatment. The target organs tend to be the brain, liver, or lung, and the approach to removing metastases in each region is different.
Surgical removal of isolated metastases is usually performed only if the operation can remove all visible areas of the disease; removal of only some of the cancer deposits in an organ will not lead to the goal of cure or long-term cancer control. When the brain is affected by one or two isolated metastases, then surgery is often feasible; this may be followed by radiation, depending on the situation. When the lungs are affected by isolated metastases, then surgery to remove the tumors may be performed even if there are numerous metastases. The lung is typically affected by isolated metastases from cancers originating in the colon and rectum, kidney, and testes, as well as from some types of sarcoma.
Chemotherapy may be given before surgery to shrink the tumors and is often given afterward to prevent new tumors from growing. Isolated metatases to the liver are mainly associated with cancers of the colon and rectum. In years past, surgeons would remove only three or fewer metastases contained in a limited part of the liver. Today, experienced liver surgeons can remove up to 80 percent of the liver to render the patient cancer-free, regardless of the number or size of the cancer deposits! Amazingly, the liver regenerates itself in a matter of weeks. Chemotherapy is often given before and after this type of surgery.
Several other techniques are used to treat cancer affecting the liver:
(1) Hepatic artery infusion, in which chemotherapy is instilled directly into the liver through an implanted pump;
(2) Chemoembolization, in which an interventional radiologist infuses chemotherapy and a substance that chokes off the blood supply to tumors (this technique is used mostly for neuroendocrine cancers and primary liver cancer);
(3) Cryotherapy, in which tumors are destroyed by freezing; and
(4) Radiofrequency ablation, in which tumors are destroyed by heat.
Rather than forming a limited number of metastases, however, most stage IV cancers form numerous cancer deposits located in various parts of the body. For example, a person who undergoes colonoscopy and is found to have a colon cancer would have a CT scan of the chest and abdomen as part of the staging workup. If numerous cancer growths are found in both the liver and the lungs, the metastases could not be removed to render the patient cancer-free. Still, it would be natural to ask, “Shouldn’t the cancer in the colon be taken out even if the metastases cannot be surgically removed?”
In regard to any newly diagnosed metastatic cancer, it is common to ask, “Isn’t there value in removing a primary tumor despite the presence of metastases?” Aside from the natural desire to rid the body of as much cancer as possible, I have heard two main reasons for patients asking about this surgery: Is the main tumor somehow supporting the growth of distant metastases in some way, like a queen bee sustaining her hive? And won’t the main tumor continue to seed the body with metastases if it is not removed?
The answer to the second question is more straightforward: although the main tumor can remain a source of ongoing metastasis, drug treatments are preferred over surgery because they will silence this process as well as treat the cancer throughout the body. Removing the primary is unlikely to improve the chances for cure and would only delay the administration of the required chemotherapy. Therefore, despite the natural inclination to remove the primary, it is not routinely done as the initial treatment.
The first question is more complicated but also more fascinating. There are animal models of human cancer (for example, human lung cancer cells capable of growing in a mouse) in which removal of the primary tumor results in rapid growth of distant metastases. These models were intensively studied, and it was determined that a substance generated by the primary tumor travels through the bloodstream to put the brakes on growth of metastases found elsewhere in the body (that is, the primary cancer inhibits growth of its own metastases). Dr. Judah Folkman isolated the first such compound and discovered that it prevented metastases from growing by blocking their ability to form a blood supply (called angiogenesis inhibitor therapy). He named the compound angiostatin, and it lit a fire in the world of cancer drug development. Today, nearly forty angiogenesis inhibitor compounds are under study for the treatment of cancer. Folkman’s discoveries have revolutionized how we think of and treat cancer.
In the real world, cancer does not often behave the same in a mouse as it does in a human. In fact, the ability of a primary tumor to slow the growth of its own metastases is not a common finding in humans; if a primary needs to come out, then it should be taken out without hesitation (an example would be a large tumor in the colon that was causing complete obstruction). The only situation in which removal of a primary tumor has been conclusively demonstrated to have an effect on survival is in metastatic kidney cancer. But this effect is a positive one: among patients with metastatic kidney cancer treated with interferon, those who first undergo removal of the primary cancer (and involved kidney) live longer than those in whom the primary tumor is left in place.
The Role of Radiation Therapy in Metastatic Cancer
When cancer is present in more than one region of the body, radiation treatments cannot eradicate it, but they can improve symptoms caused by tumors in specific areas. Radiation therapy can be given to virtually any part of the body. Two of the most common uses of radiation in the treatment of metastatic cancer. Radiation therapy is the mainstay of treatment for cancer metastases affecting the brain. In this situation, whole brain radiation therapy (WBRT) is typically given daily, five days a week, for two or more weeks. A steroid medication called dexamethasone (Decadron) is usually prescribed during treatment to decrease the swelling that typically surrounds metastases and which may worsen during radiation. Typical side effects of WBRT include reversible hair loss (the hair takes a good number of months to return), temporary scalp irritation, and mild weakness.
Memory impairment and other neurological side effects are uncommon. Overall, WBRT is surprisingly well tolerated and generally does not impair the patient’s functional level during treatment. As with all cancer therapies, if the cancer is causing symptoms (brain metastases may causeheadaches, imbalance, nausea, weakness, and specific neurologic impairment), then the therapy will greatly improve a person’s condition.
If isolated brain metastases (usually no more than three) are present and surgery is best avoided, then stereotactic radiosurgery (a form of radiation, not surgery) can be performed. This focuses high-intensity beams on a small region of the brain. WBRT may be used before or after this procedure in an effort to prevent new brain lesions from developing in regions outside the stereotactic field. The radiation oncologist and neurosurgeon will coordinate the best plan of attack on brain metastases.
The use of chemotherapy and targeted therapies to improve the effectiveness of radiation against brain metastases is being tested. Individual areas of cancer metastases in the bones and around the spinal cord may also be treated with radiation therapy, especially if they are causing pain, difficulty walking, or specific neurological symptoms.
Patients with bone metastases may also receive regular infusions of a bone-strengthening drug, such as zoledronic acid (Zometa) or pamidronate (Aredia), which decrease the risk of fracture caused by the cancer. It is critical to seek consultation and care with a medical oncologist before beginning radiation treatments for a cancer that has metastasized (unless treatment is urgent) so that the sequencing of radiation with other treatments that may be needed (such as chemotherapy) can be optimally planned. In many treatment centers, radiation oncologists and medical oncologists are within walking distance of one another, which facilitates good and timely communication about the treatment plan for their patients; the multidisciplinary care of cancer patients is also coordinated at regularly scheduled hospital tumor boards.
In summary, the appropriate treatment of any cancer is dictated by specific aspects of the cancer as well as the health and preferences of the patient. Cancer treatments given with the intent and possibility of cure (adjuvant and neoadjuvant therapies, some metastatic cancers) should be given at the recommended doses; they are administered over a finite period. On the other hand, there is more flexibility in the administration of treatments for metastatic (chronic) cancers: the treatment period is indefinite and may be off and on for the remainder of a person’s life. As tremendous advances in science bear fruit in the everyday treatment of people with cancer, survival will continue to improve and many more people will be living with the disease.
We must always keep in mind, however, that the goal of treatment in these situations is not to extend one’s suffering but rather to improve one’s quality of life and diminish cancer-related symptoms; when this occurs, enhanced survival is sure to follow.
Cancer Treatments at Work
At the end of a hectic day not long ago, I was asked to consult on an urgent case: an eighty-eight-year-old hospitalized patient who was in a coma. The referring doctor, a caring physician, stated bluntly, “He’s very sick and close to death. The scans show widespread cancer, though we haven’t done a biopsy. Given his age, I think the best way to proceed is hospice, and I’ve recommended this to his sons. They’re very realistic but want to meet with an oncologist for closure.” The patient, Abe, was a retired dentist who had been living with his wife in another state. For some time he had been experiencing fevers, weight loss, and progressive weakness. But because his wife had Alzheimer’s disease and he looked after her, he neglected his own declining health. The couple’s sons had recently visited them and immediately insisted that their parents return home for medical care. By the time Abe was examined by a physician, he required hospitalization; he was too weak to walk, was becoming confused, and soon after lost consciousness.
I encountered a long, gaunt, handsome man in a hospital bed; he had a shock of white hair and few wrinkles, appearing younger than his age. His temperature was 103 degrees and he was clammy to the touch. He did not open his eyes when I called his name and only moaned when I shook him. CT scans to locate a source of fever had revealed a tumor the size of a volleyball in his abdomen, smaller tumors in his chest, and widespread involvement of the bones. The situation was grim. According to his sons, Abe had been alert and clear thinking until the current illness. They wanted to know whether there was any chance he could improve and whether it was worthwhile to pursue a biopsy to determine the type of cancer he had. I told them that it probably wasn’t, adding that I rarely said this. Given his age, debilitated condition, and widespread malignancy, even a very treatable cancer such as lymphoma would probably not turn around in time. The chances of success were low.
And how would we define success? If we could shrink the cancer but Abe remained in a coma, would we have helped him? What if treatments only prolonged his suffering? Certainly the case could be made for being humane and letting him pass, since he was so close. They acknowledged all of this and said they would confer and get back to me with their decision.
Not long after, they called. “Dad was always a fighter and tough as nails. He would want to know what he had. And he would want to try to fight. We can’t let him go without at least knowing what he has. That would not be honoring the way he lived his life, the way he taught us to be. So let’s do the biopsy, let’s go for it.” I replied, “Fine, let’s do it. But we have to act quickly. I want the biopsy done this afternoon so we can have a result by tomorrow.”
The diagnosis was large cell lymphoma. “I can’t predict whether the cancer will respond to treatment or if he’ll wake up,” I told them, “but he probably won’t experience severe side effects from the recommended chemotherapy. If we’re going to try, let’s do it right and give him every chance.” Again they conferred and said that they would get back to me. I got the call: “Fire away.” We administered CHOP-Rixutan therapy and hoped for the best. I saw Abe the next morning on my rounds, and his fever was down attributable to the steroid medication he received as part of the treatment.
He looked more comfortable but was still unresponsive. His sons milled around the halls while his wife sat by his side, quiet and pensive. I returned the next day to find no change. I saw him on the third, fourth, fifth, and sixth days following treatment. He lay motionless in the bed, with no signs of improvement. All I could do was counsel his family. On the seventh morning, I made my rounds early. The hospital was quiet, and Abe was alone in his room. I stood at his bedside and performed my usual examination. Out of habit, I called his name, not expecting a response. There was none. But as I turned to leave, he sprang bolt upright, opened crystal-clear blue eyes, and blurted out emphatically as he tapped on his right temple, “My name is Abe, and I have all my marbles!” I was flabbergasted. He continued and became choked up, “Thank you, doctor, thank you for all you’ve done.” I was floored, tongue-tied, and choked up, too. “Well . . . I can see that you do . . . have all your marbles! You are so welcome!” Abe received additional treatments and achieved a remission of his cancer. He enjoyed more time with his family and actually survived his wife; he died not long after she did of causes unrelated to cancer.
I relate this story to illustrate the sometimes dramatic results that can be obtained with effective chemotherapy
