The Price of Hope: Medicine's Disputed Frontier - A Special Report; Patients and Insurers Clash On Therapy's Outer Limits
By Erik Eckholm
Last fall, two months after the birth of her second child, Marie McCook of Philadelphia discovered she had breast cancer that had spread into her neck. Her prognosis was poor, but her doctors told her she was a suitable candidate for a dangerous, unproved and costly therapy under study, a bone-marrow transplant that would allow them to bombard her body with huge, otherwise lethal doses of anticancer drugs. She grasped the slender reed. "I feel it has given me an opportunity at a possible cure," Mrs. McCook, 35 years old, said of the $100,000 procedure. It was performed this spring at the University of Pennsylvania Cancer Center, and while her cancer has melted away, she will not know if she is cured for years. The bills were paid by her health insurance company, which is supporting the study. Denial and Near Death Evelyn Harper, 47, with two children, learned last fall that her breast cancer had invaded her eyes and liver. A resident of the Virgin Islands, she sought treatment in Los Angeles, where doctors said she too should consider a marrow transplant. But her insurer, like many around the country, said it would not cover an experimental therapy. In February she appealed, sending reams of data provided by her doctors arguing that the procedure might give her a 20 percent chance of surviving cancer-free for years. At the end of May the appeal was denied. By then the cancer had spread too widely to consider a transplant and now, with no hope of effective treatment, she is near death. "That might not have sounded like a big chance of success, but it's a lot better than nothing," said her husband, Dennis Harper. "It seems like the insurance company holds you off as long as possible, waiting until it's too late for a transplant. That's not right." Whether insurers should pay for marrow transplants has already become tinder for bitter lawsuits, poignant talk shows and an emerging political movement of breast cancer patients. The debate exemplifies the wrenching issues that may increasingly bedevil American medicine in an era of fast-changing, enormously expensive treatments and rising concern about costs. Benefits vs. Costs Health experts and government leaders, as well as insurers, hope to tame runaway medical expenses through more stringent assessment of new treatments and by weighing their benefits and costs. The concepts sound sensible and uncontroversial -- until they are applied to real people, especially with life-threatening diseases like breast cancer, and to promising treatments being urgently refined, like marrow transplants. Grueling ordeals that put patients through at least three harrowing weeks of hospitalization, transplants have already proved useful against certain cancers of the blood, and insurers generally pay in those cases. Doctors are now trying the therapy in patients with several other kinds of cancer, including ovarian, testicular and especially breast cancer. Some patients have shown encouraging responses, but many have not. The mortality rate from the procedure itself, while improving, is still 5 percent or more. All the researchers agree on the need for more research, but they put different shades on the same skimpy facts. "For the right patient, I think it should be considered a therapeutic option," said Dr. William P. Peters, director of the Duke University Medical Center's marrow transplant program, a leader in research on transplants for breast cancer and a critic of insurance companies that refuse to pay when the procedures are performed at experienced centers. Other experts are skeptical. "We have raised the public's expectations far beyond what is supported by the published data," Dr. I. Craig Henderson, director of the breast evaluation center of the Dana Farber Cancer Institute in Boston, wrote in The Journal of the National Cancer Institute this summer. "We have no evidence as of yet that any patient will be cured by this therapy who would not have been cured by more conventional treatment." Hundreds of women with breast cancer this year will endure the transplants and accompanying blasts of drugs. Researchers believe at least 10,000 women a year, of the more than 40,000 who die from breast cancer annually, may be good candidates if the procedure is shown to help more than it hurts. Clinical Trials Under Way Most women whose cancer is caught in early stages are cured with conventional treatments, including removal of the cancerous lump or the entire breast, along with drug therapy and radiation. For them, there is no reason to take on the risk and travails of a marrow transplant. Many more women are ruled out as transplant candidates by age and condition. Because it is so demanding on the body, the procedure is seldom tried on women older than about 55, or on those with other medical problems. Firm answers about effectiveness are several years away: controlled clinical trials, comparing patients receiving transplants with similar women receiving conventional chemotherapy, have just begun. The procedure is becoming safer and less expensive, but even at best, research suggests, it will never offer a miraculous cure for patients with advanced breast cancer; it will, however, raise their odds of survival. For advanced breast cancer, it appears that transplants will, at best, keep 10 to 20 percent of the women cancer-free, said Dr. Edward A. Stadtmauer of the University of Pennsylvania Cancer Center, who is treating Mrs. McCook in a study comparing transplants with traditional drug therapy. And that success rate may fall, he said, as more patients are followed for more years. "That still would be wonderful," he said. "But we also have to look at quality of life, toxicity and costs. I have to say I still don't know which group in the study is going to do better. There is truly no right answer in 1991." With known therapies offering little, some patients see the unknown in a different light. "There's a whole list of things that could go wrong, and yes, it scared me," Mrs. McCook said. "But I also have two small children, and the chance of not being here in 10 years also scares me." The Controversy State of the Art Or Experimental? Insurance companies have long said they do not cover unproved therapies, but they have often paid for innovative, unapproved uses of cancer drugs. In decades past, too, they started paying with little question for costly new procedures, like coronary bypass operations, that were widely adopted with little evaluation. But today, expensive new procedures receive much closer scrutiny. The official position of the insurance industry on transplants is clear enough. "We are not saying this is too expensive and it shouldn't be covered," said Naomi Aronson, director of technology assessment with the Blue Cross and Blue Shield Association in Chicago. "We are saying that procedures need to be evaluated so that precious health care resources can be used for things that are effective." If studies provethat transplants improve survival, Dr. Aronson said, the companies will pay. Many Insurers Are Paying To speed the search for answers and perhaps fend off lawsuits, many Blue Cross affiliates and, in the Philadelphia area, U.S. Healthcare, a large health maintenance organization, have agreed to contribute to the costs of patients' receiving transplants in certain clinical trials. In practice, after hearing pleas or threats from doctors or lawyers, many insurers are paying transplant bills for some breast cancer patients, but many, too, are denying coverage. Recently, some insurers have begun writing policies that specifically exclude coverage of marrow transplants for breast cancer. Cancer researchers, as well as desperate patients, are angry. "It's unfortunate, because basically they are holding transplants for breast cancer up to a different standard than other costly procedures," said Dr. Karen H. Antman, director of the transplant program at the Dana Farber Cancer Institute. Insurance officials deny they have a double standard. "It will be impossible to do studies unless patients have coverage," Dr. Antman added. Ellen Hobbs, a 36-year-old breast cancer patient in Sacramento, Calif., said: "What's the difference between experimental and state of the art? The doctors told me that traditional chemotherapy would be ineffective." "This country spends a lot of money fixing up people with no hope," said Mrs. Hobbs, who had a transplant in June and became politically active after fighting for months, with the help of a lawyer, before persuading her insurer to pay. Now receiving radiation therapy in followup treatment, she is doing well so far, but, like Mrs. McCook, cannot know her long-term prospects since cancer cells can lurk in the body for years before resurging. The Transplant Bombarding Body With Cancer Killers For such a trying ordeal, the transplants involve a series of undramatic steps. Doctors have long suspected that in some patients they could kill cancer in the body by dousing it with enough toxic drugs. The problem was that this would kill the patient, too, by destroying the marrow cells that generate vital red and white cells and platelets in the blood. In autologous marrow transplants, as these are called, some of the patient's own marrow cells are extracted from bone or blood and frozen; outside donors are not needed. The patient is then subjected to several days of intensive chemotherapy, 10 times the normal dose. Her marrow cells are reinjected, and the real drama begins. For weeks, until the reinjected marrow begins producing new blood cells, assuming it does, the patient lives without much of an immune system, susceptible to vicious fungal, bacterial and viral infections. "It is horrible," Mrs. McCook said. "Everything just hits rock bottom. I had temperatures of 105, vomiting, bowel problems and I needed morphine. You lose your hair and your appetite, you lose your taste buds. You get depressed." Vulnerable Period Shortened Until recently all patients spent more than a month in the hospital and transplant-related mortality at some leading centers was over 20 percent, most often from infections. But the recent availability of growth factors, manufactured versions of natural body chemicals that stimulate the marrow cells, has shortened the period of critical vulnerability, reduced hospital stays to as little as three weeks and pulled down death rates to 5 percent to 15 percent at various centers. The growth factors have also pulled down the cost, which is attributable more than anything else to the length of the hospital stay. Dr. Antman said cost for some patients at some centers was down to $70,000 or less. Dr. Peters believes that over the next several years the price could fall to $25,000 or less. The Results Encouraging Signs But Doubts Persist Right now, transplants are considered worth risking for the several thousand women each year whose cancer has spread to 10 or more lymph nodes, meaning that they a high chance of relapse after normal therapy. It is also considered worth the risk for the smaller number of women with large tumors that cannot be surgically removed or with inflammatory tumors and for the tens of thousands of women whose cancer has already spread to other parts of the body, who are rarely cured. Among those groups, only some can even potentially benefit. Before a transplant is considered, a woman is given a course of conventional chemotherapy. Only those whose tumors shrink in response to lower doses, studies have found, may potentially be helped with the all-out attack of high doses and a marrow transplant. Will Remissions Last? In a positive sign, studies indicate that women receiving transplants are far more likely than others to show a good short-term response -- disappearance of detectable cancer. The open question is whether these remissions will last. Dr. Peters and other researchers point to encouraging recent results from studies involving limited numbers of patients. In one recent study at Duke, among 59 women whose cancer had spread to 10 or more lymnph nodes but not more widely, three-fourths were cancer-free after four years, he said. With conventional therapy, he said, he would only expect about one-fifth of such patients to be cancer-free. Among a group of 45 transplant patients whose cancer had already spread to distant sites beyond the lymph nodes, he said, 20 percent are cancer-free after an average of four years. With conventional therapy, almost none with such advanced disease would be cancer-free at that point, he said. Of another group of 22 women with advanced cancer who were early pioneers with the therapy, three remain cancer free after five to eight years. But others say figures like these, while intriguing, may easily mislead. "The question is, what would have happened to those same patients if they had gotten conventional chemotherapy," said Dr. David M. Eddy, a health economist at Duke University who is a consultant to insurance companies. "I can show you individual patients who received conventional therapy who also survived 5 or 10 years." Among other problems with existing comparisons, the patient groups may have differed in important ways. "The transplant patients are very healthy, good candidates for treatment," noted Dr. Bruce D. Cheson of the National Cancer Institute. Dr. John H. Glick, director of the University of Pennsylvania Cancer Center, says four or five years is not long enough to say a patient is cured of breast cancer. "Some of the advocates are speaking too soon," he said. The Outlook Weighing Lives Against Costs Within three or four years the clinical trials should yield convincing evidence about the comparative effectiveness of transplants, although it will take longer to know whether cures are achieved. If a statistically significant survival benefit is shown, even for a few years, then the insurance dispute may fade away. But, depending on how dramatic the trial results are, divisive questions of cost versus benefit may persist. "If there is a big difference in survival, then it will be persuasive," said Dr. Cheson of the National Cancer Institute. "But if there is only a small advantage for transplants, it's still going to be an individual decision the physician will have to make with the patient." Even the insurance industry has shied away from the more explosive, but ultimately unavoidable issue for American medicine: How good does a treatment have to be to make it worth the price? Benefits to Bring Pay In the case of marrow transplants, insurance companies have said that if studies yield proof of benefit, they will cover the procedure whatever it costs. But some experts wonder whether this approach will remain feasible, or even wise. "I think they should take the cost into account, and weigh it against the benefits," said Dr. Eddy, the health economist. "I think in five years they will do that, but they don't now." "Somewhere, some time, someone will have to judge what additional benefit is worth what additional cost," Dr. Eddy said. He acknowledged that this would be treacherous new terrain for government, insurers, doctors and patients who, like Mrs. McCook, put a value on hope itself. "Society has had very little experience doing this," Dr. Eddy said.
