Beating A Killer
Cancer was once the end of the line. Today, it can be managed and defeated
In 1997, Joe Fred Starr was a vigorous and successful 63-year-old businessman in Fayetteville, Ark., when he became one of the 200,000 men who are diagnosed every year with prostate cancer. Starr knew prostate cancer was a killer. Each year nearly 30,000 men die of the disease, and among cancers it's second only to lung cancer in claiming male lives. So he opted for the most aggressive treatment possible. "I was chemically castrated," he says simply, when describing the hormonal oblation treatment that made his PSA level drop to zero. "It was a choice between a knife and an old man's ego."
The first year after diagnosis, Starr was so busy reading everything and finding the right doctor that he didn't have time to think of much else. But then, he says, "a kind of sadness built": The treatment "makes you feel kind of grubby, you gain weight, and they take all the testosterone out of you." Two years passed, each one cancer free, yet the second more desperate than the one before. He remembers driving around southern Colorado visiting family, in such despair that he couldn't sleep and was crying uncontrollably. At one point, Starr walked into a pawnshop, not having slept for days, unshaven, his face streaked with tears. He asked to buy a gun. The owner looked up and said, "You crazy son of a bitch, you are buying a gun to kill yourself, and I am not selling you one. If you want to kill yourself, go drive into that lake back there." Starr didn't drive into the lake but headed home instead. Finally, he found a psychiatrist who could address his depression, the price he paid for surviving his cancer.
The stories of cancer victims vary widely, but the basic scenario is always the same. First comes the terrifying diagnosis: cancer, the big C. The news is followed by some combination of surgery and/or chemotherapy and radiation treatments. Then there's the fear and the terrible sadness, compounded by the nausea and bone-wearying fatigue. And, of course, there's the existential loneliness at 3 in the morning.
And yet, after all that, perhaps in six months or a year, life once more begins to lose its blur and hold promise. Hair, scorched by chemotherapy, returns--though sometimes with a surprisingly different color and texture. The birthday party that was an impossible dream six months before is now a treasured gift. The return to normal life comes with visits to the oncologist's office and the unavoidable counting: six months later, one year later, two years later, and, finally, the triumphant five years later--the marker of a successful cure. Case closed. Another cancer patient, miraculously, has become a survivor.
Sea change . But can life after cancer ever be said to be truly normal? It's not just the emotional stress of living beneath a diagnostic sword of Damocles. Even after cancer no longer inhabits the body, the treatments that conquered it often leave in their wake debilitating physical and emotional scars. Or simply a profoundly changed approach to life.
Nearly 10 million Americans, from the halls of the Supreme Court to the pueblos of New Mexico, are living with cancer. Most were diagnosed five or more years ago; many who would have died just 15 or 20 years ago are alive today, raising families, leading productive lives. Yet doctors are only now beginning to study these survivors and to understand how the very therapies that cured them can also create a whole new set of problems--some, many years later. Joe Fred Starr never seemed to have had a melancholy moment in his life until after his cancer treatments. A young man in his 20s might beat testicular cancer only to have heart problems in his 40s. A 65-year-old breast cancer survivor might experience confusion and memory problems. Not to mention the fatigue, pain, and sexual dysfunction that can haunt survivors of all ages.
In response to the burgeoning needs of cancer survivors, the federal Centers for Disease Control and Prevention and the Lance Armstrong Foundation will release in April a public-health blueprint for addressing the needs of cancer survivors. New York's Memorial Sloan-Kettering and Boston's Dana-Farber have both launched "survivorship" programs in the past six months. M. D. Anderson and the University of Pennsylvania have had such centers for a few years. The field is still in its infancy, but such programs are sensitizing more doctors to the demands of cancer survival.
One major source of later problems is radiation. In 1981, researchers at the University of Pennsylvania reported that kids with leukemia suffered significant drops in IQ when their treatment regimen included head irradiation, the standard of care at that time. Mark Kieran, director of pediatric neuro-oncology at Dana-Farber, remembers walking into a clinic in 1992 to see a 20-year-old follow- up patient who was "cured" of pediatric brain cancer 15 years before. He was rocking back and forth in a chair, sucking his thumb. "From a statistical point of view, he was a survivor," Kieran says. "But when we treated him, we just didn't know what the damaging effects of the therapy would be, because no one survived." As evidence mounted, however, doctors found it wasn't necessary to radiate the entire head. Today, happily, such patients have a much better prognosis.
Brain cancer accounts for approximately 17 percent of all cancers among those under age 20, which means there will be more than 2,000 new cases diagnosed this year. Between 1974 and 1976, about half of the children with brain cancer survived; between 1992 and 1998, nearly 70 percent did. A child's developing brain is highly vulnerable to the assault of radiation, because new neural connections are occurring so rapidly. Indeed, Lisa DeAngelis, head of neurology at Sloan-Kettering, says that today, even if radiation is deemed the best treatment for a child under 2, "we still don't do it, even if we are buying time." Researchers have found that the brain's white matter--the region most involved in higher cognitive function--takes the brunt of the damage from radiation. Radiation works by damaging a tumor's genetic material so it can't continue growing. It was once thought that healthy tissue surrounding the tumor would survive such a chemical assault, and in some parts of the body that's true. But it turns out that the delicate white matter of the brain is not so resilient.
There are other problems associated with radiation. A recent study of nearly 1,400 kids diagnosed with Hodgkin's disease between 1955 and 1986 shows they have 18 times the risk of developing another cancer--most commonly breast or thyroid tumors--as do healthy people. Again, radiation was the culprit.
Research on young survivors has also shed some light on the unanticipated hazards of chemotherapy. Testicular cancer, for example, which usually strikes men in their 20s, is 95 percent curable. But the chemo regimen used, which includes an ingredient called cisplatin, has some bad effects on the kidneys and, perhaps, the heart.
While most of the insights into long-term survivorship come from children, adults offer another useful perspective on these late effects. In 1971, Ellen Stovall was 24 years old and had just given birth four weeks before when she was diagnosed with Hodgkin's disease. This cancer starts in the lymph system and attacks the body's immune and blood production systems. At its worst, the cancer spreads and can destroy the lungs and the liver. Stovall was told that she could hope, at best, to see her daughter's second birthday.
With massive radiation treatment, Stovall survived. What she was not told, however, was that the treatment that saved her life would also throw her into immediate menopause. There was no discussion of banking her eggs--it simply wasn't an option at the time. Indeed, no one thought that she would live long enough to suffer any long-term consequences that come with 30 years of menopause. She developed both cardiac arrhythmia from radiation and premature aging of her organs. And on top of that, she watched her friends have their second and third babies, and became more and more disconsolate. She found herself feeling forgetful, disorganized, generally less competent.
Stovall isn't alone. It's not just the trauma of cancer but also the long-term effects of the chemotherapy and radiation. Once it was believed that the brain was protected from the toxins of chemotherapy by the "blood-brain barrier," a layer of cells that, theoretically, prevents large molecules in the bloodstream from invading the brain. But this protective barrier isn't foolproof; it can be broken down by, among other things, radiation and inflammation that many of the chemotherapies cause. The result is called "chemo-brain," characterized by maddening memory loss and compromised "executive function"--that is, as Stovall recognized, the ability to organize and juggle tasks.
Puzzles. None of the results of the chemo-brain studies are crystal clear. No one really knows, for example, why the cognitive problems show up. Is the impairment the result of the chemotherapy or of the stress and anxiety associated with simply having a cancer diagnosis? Or are some people simply predisposed genetically to suffer cognitive decline? A recent study suggests that one possible risk factor for chemotherapy-induced cognitive decline is the presence of a gene called APOE, which is also associated with increased risk for Alzheimer's disease.
Clearly, it's not just the brain's cognitive functions that are affected. As with Joe Fred Starr, depression for cancer patients and survivors is another serious problem. In the past, depression in cancer patients was underdiagnosed and undertreated. "There was a popular misconception that everyone who gets cancer gets depressed," says William Breitbart, the chief of psychiatry at Sloan-Kettering. But in fact, he points out, the kind of depression experienced by Starr is shared by just 15 to 25 percent of other cancer patients. Some cancer patients do become sad, some become anxious, while others go through what can only be called a grief reaction. But a large majority of cancer patients don't suffer clinical depression at all. And when they do, it can be successfully treated. "I can honestly say now that I am happier than a lot of my friends are," Starr says. "And they don't have anything wrong with them." He exercises; he travels; he lives a full life with his wife. And while he acknowledges that some days are better than others, "it was just time to stop feeling sorry for myself and realize I didn't want to take that old man's advice and drive into a lake."
Starr's experience is repeated often by cancer survivors and the psychiatrists who treat them: The depression itself can often be worse than the disease, and once the depression is under control, life as a cancer survivor gains hope and meaning. A number of provocative research avenues are being explored in the area of depression and cancer. Often the listlessness, the lack of appetite, poor concentration, and sleeplessness can be part of a depressive illness, but they can also be symptoms of the cancer itself--what's called a "sickness syndrome." But could that syndrome respond to antidepressant medication? Can depression be considered a risk factor for cancer? Does the disease of cancer itself, like in pancreatic cancer, set off mechanisms that trigger depression? These are all questions still unanswered.
Clues. In trying to answer these questions, scientists have come up with some fascinating findings. One possibility has to do with body chemicals called cytokines, which are secreted by the immune system to fight off infection and disease, including cancer. Researchers at Emory University have found elevated levels of cytokines in medically ill patents with depression, and those levels correlate with symptoms of sickness behavior. Cytokines are ingenious in the ways they can cause depression or sickness behavior, insinuating themselves in a number of different brain pathways and wreaking biochemical havoc. It's not entirely clear, however, what comes first. In pancreatic cancer, for instance, one theory is that the cancer itself creates the cytokines. Nearly half of people with pancreatic cancer are depressed, and not just because they found out they have a disease with a poor prognosis. Indeed, the depression precedes the cancer diagnosis and is one of the symptoms of the illness.
A number of cancer treatments are based on cytokines. As Andrew Miller, director of psychiatric oncology at Winship Cancer Institute at Emory University, says, "What is clear is that there seems to be a connection between circulating levels of cytokines and behavior, but we don't know the directionality of that relationship."
Interferon is one of the usual treatments for melanoma, and it also triggers these cytokine storms. In one of Miller's studies, half of the 40 patients soon to be treated with interferon were given an antidepressant, and the other half were given a placebo. After three months on interferon, 45 percent of those on the placebo developed clinical depression, while only 11 percent of those on an antidepressant did. Does that mean a better long-term prognosis for those patients? No studies prove this, and doctors are emphatic about pointing out that succumbing to the disease cannot be seen as representing a failure of will on the part of the patient. "There have been headlines for many years that you needed to cope better if you wanted to live longer," says Dwight Evans, professor of psychiatry and neuroscience at the University of Pennsylvania School of Medicine. "As important as coping may be, I have had patients whose surviving family members actually felt responsible for their loved one's death, as if something had gone awry in family home relations. And in the end, you have two victims: one who succumbed to cancer and the other who tried to help but believed he failed."
Quality time. Even if treating depression does nothing to improve long-term survival, it goes to the heart of improving the quality of a cancer survivor's life. Miller and others would like to have depression, fatigue, and cognitive problems considered as a sixth vital sign in patient care--along with respiration, blood pressure, pulse, temperature, and pain level. Says Miller: "When we think of vital signs, we should include all behavioral signs, so that patients who are having symptoms can be referred to an appropriate physician."
Pain in itself may not stop when treatment ends. "You can have symptoms that go on for years, whether from the tumor itself, chemo, radiation, or surgery," says Ada Jacox, professor of nursing at the University of Virginia and director of clinical practice guidelines for the American Pain Society. Shingles can flare up in older cancer survivors and become a chronic problem. Nerve pain, called neuropathy, can occur if you're placed a certain way on an operating table during surgery. Women can have long-lasting pain from constricting tissue after a mastectomy.
The feedback loop between pain and depression is sometimes difficult to untangle. Indeed, the nerve tracks that receive pain and those that channel emotion are very closely connected in the brain. Studies have shown that previous episodes of depression predispose a patient to the development of chronic pain, and preliminary evidence suggests that pain may indeed become chronic because of the close connection between these two tracks. University of Miami psychiatrist David Fishbain says, "There is good evidence that if you treat patients who are depressed, you will make them less sensitive to the pain stimuli. They may focus on it less, and they will just tolerate their pain better."
Fatigue is another complication. Pam Massey, who runs the rehabilitation center at M. D. Anderson in Houston, says her team has found that the severe fatigue experienced by bone-marrow-transplant patients can be lessened with exercise. Massey's team added carefully supervised conditioning to its regular outpatient therapy sessions. "You'd see patients on treadmills," she says, "or sitting on exercise bikes with IV poles and five or six bags hanging from them."
Massey also helps patients handle their lymphedema, the painful and disfiguring limb swelling reported by nearly half of breast cancer survivors treated with radiation who are at least 15 years beyond treatment, as well as survivors of melanoma, cervical, and prostate cancer. "We can't tell whether it will start or when," she says. The disruption of the lymphatic system, which can come either from pressure from the tumor or from treatment like surgery or radiation, can be treated, she says, with special exercises, physical therapy, and compression bandages.
Survivorship. The main message from doctors to patients is: Speak up. And sometimes it's imperative to raise questions before treatment begins, as in the case of patients concerned about their future fertility. Many women can bank eggs, and even young boys can have sperm banked. The bad news: Surveys show about half of men and women don't remember being warned about infertility at the time of diagnosis or treatment. Lindsay Nohr, diagnosed with tongue cancer in her 20s, found it frustratingly difficult to explore all her options under time pressure. After doing her own research, she had her eggs frozen, then founded Fertile Hope as a source of information for other young patients. About 100 babies worldwide have been born following egg freezing. Even more cutting-edge techniques are on the horizon.
With this host of potential long-term effects--from depression to fertility, from cognitive impairment to cardiac problems--one of the biggest questions for cancer survivors is who should provide follow-up care after the regular oncologist visits end. The new survivorship centers aim to serve as one-stop shopping, with monitoring of recurrence and late effects, psychologists and social workers, genetic counselors and fertility experts all in one place. But they aren't accessible to most Americans, who are treated in their communities, not in major cancer centers.
Primary-care physicians and specialized nurses may be the best bet for most people, but whoever ends up providing the care needs to know what to look for. Once again, while there's a thick sheaf of recommendations for following up children, there's not much for adults. "One of the areas still lagging behind is research looking at least five years post diagnosis, about which we know very little," says Julia Rowland, director of the Office of Cancer Survivorship at the National Cancer Institute. It's starting to happen: The National Institutes of Health has increased funding of survivorship studies, and there's new interest in the field. And the president's cancer panel will issue its first report this year. But the primary source of information on late effects is, for now, the survivor community itself.
Jay Goldberger is just one beneficiary of this new expertise. At 27, he was told that the avocado-size tumor lodged between two major arteries in his nasal passage was a rare, inoperable pediatric sarcoma with a prognosis of six months. Desperate for time, Goldberger and Esther, his wife of two years, moved from Minneapolis to Houston for treatment at M. D. Anderson. The doctors gave Goldberger a powerful, experimental wallop of chemotherapy. "The doctor told me I'd keep getting the first round of chemo until I told him to stop," says Jay. "He said, `You'll know when to tell me to stop because you'll feel like you're about to die.' " One day, that's exactly how he felt.
The Goldbergers stayed in Houston for six months. When they returned home, Jay weighed 130 pounds, down from his usual 200. The chemotherapy had so weakened the healthy tissue in his neck and jaw that he was left with persistent jaw pain, and the drugs so damaged his salivary glands that he must chew gum constantly. But the couple had banked sperm, and after Jay improved, Esther conceived and gave birth to twin girls. When the girls were just 2, Esther was diagnosed with non-Hodgkin's lymphoma. She was also successfully treated at M. D. Anderson, and after finishing chemo she got pregnant the old-fashioned way and gave birth to a boy. Now she's pregnant again, with their fourth due in July.
Those conceptions should have been impossible. But their story shows that what happens on a physiological level may be only partially understood and impossible to predict. In the end, when the diagnosis is given to you or to someone you love, it changes everything. Says oncology nurse Catherine Harvey: "We are now only beginning to understand that how you live with the experience is more important in many ways than how you die."
That's exactly the way Joe Fred Starr sees it. "I have been alive for almost seven years," he says, a ring of modest pride in his voice. "There is no cure for prostate cancer, but I have a decent prognosis, and mentally I am clearheaded, even happy. I am almost what they call a poster child."
This story appears in the April 5, 2004 print edition of U.S. News & World Report.