For my hale and hearty father-in-law, the first sign that something was wrong occurred at 88 years of age, when his ever reliable tennis serve kept landing astray. A series of medical tests soon revealed the worst: advanced, metastatic pancreatic cancer. Treatment might buy him a little time, his doctors told him, but that prospect did not outweigh his dread of spending his final days in a toxic and debilitating haze of chemotherapy. He quickly opted for hospice care and died with dignity less than two months later, surrounded by loved ones.

My own father learned he had bladder cancer at 91 and made a very different choice. He underwent the full trifecta of treatment: surgery to pare down a tumor that had already penetrated the bladder wall, plus seven weeks of chemotherapy and 35 radiation treatments to destroy lingering cancer cells. There were times when he regretted it, complaining of weakness and torpor, but 20 months after completing the clinical gauntlet, he is alive and going relatively strong, considering he is 93. His sister made a similar decision when faced with lymphoma at 88; she, too, is a survivor—at 91.

Twenty years ago few oncologists would have attempted aggressive therapies with 90-year-olds. No one used the term “granny death panel,” but people in their ninth and 10th decades of life were seen as too fragile for treatment. Their cancers were often believed to be so slow-growing that something else might kill them first; it made little sense to put them through the ordeal and cost of treatment.

Those ideas have since largely fallen by the wayside. Now, as my own family experience suggests, the elderly—especially the very old—are the fastest-growing group of cancer patients in the U.S., thanks mostly to the aging of the general population, better screening, improved therapies and other changes in medical practice. More than half of U.S. cancer patients are older than 65, and by 2030 that figure will rise to 70 percent, according to a 2012 analysis. Understanding differences in how cancer develops and behaves in the elderly and determining which older patients can benefit from treatment—and which ones lack the resilience to tolerate it—are therefore increasingly urgent issues. Fortunately, research is beginning to answer these questions and provide badly needed tools for doctors, patients and families facing complex decisions about treatment.

A Disease of Aging
Live long enough, and chances are about 40 percent that you will develop a potentially life-threatening malignancy. Although cancer certainly can and does strike young people, it is, by and large, a disease of aging—and the leading cause of death in Americans between 60 and 79 years old.

Risks for most types of cancer increase as we grow older for at least three reasons. First, we experience more cumulative exposure to the things that mess with DNA in ways that can lead to malignant growth: sunlight, radiation, environmental toxins and noxious by-products of metabolism. Second, older cells are more vulnerable to this damage—or less able to repair themselves. “Most aging cells develop genomic changes that make them more susceptible to the carcinogens in the environment,” says oncologist Lodovico Balducci, who studies and treats cancer in the elderly at the Moffitt Cancer Center in Tampa, Fla. Third, the various housekeeping systems—such as the immune defenses—that keep our tissues healthy begin to break down with age, the equivalent of watchdogs falling asleep.

The old idea that cancer is less aggressive in the elderly is not entirely without merit: breast and prostate cancers tend to grow more slowly in older patients. But other types—colon and bladder cancer and certain leukemias, for example—are usually more aggressive and harder to treat. This may in part be because of certain age-related genetic mutations.

An older body also provides a different internal environment for the growth of cancer cells than a younger body does. Whereas the drop in estrogen and other sex hormones that occurs with age can slow the development of some breast and prostate tumors, at least one other common endocrine change—rising levels of insulin—does the opposite, stimulating tumor growth. In addition, older tissues tend to exhibit more chronic inflammation—a low-level infiltration of immune cells and substances. “This hallmark of many old tissues,” explains Judith Campisi of the Buck Institute for Research on Aging in Novato, Calif., “will generally promote the growth of cancer.”

No wonder, then, that people who are 75 and older have the highest cancer rates of all age groups. According to 2010 figures from the U.S. Centers for Disease Control and Prevention, tumors with the potential to invade other tissues are nearly three times as common in people 75 and older as in individuals between ages 50 and 64—and that does not include common skin cancers (basal and squamous cell types) that tend not to spread deep within the body and that also become more pervasive with advancing age.

Getting Treatment Right
Despite the prevalence of cancer in the elderly, treatment studies rarely include people older than 70, leaving doctors without clear guidance on what works best for such patients. “In geriatrics, we are always having to extrapolate from treatment guidelines based on younger people, but the gap is most extreme in cancer care,” says Holly Holmes, a geriatrician—or specialist in aging—at the University of Texas M.D. Anderson Cancer Center. That gap may finally begin to close in the years ahead. In September 2013 a report on the “crisis in cancer care” from the Institute of Medicine recommended offering drug companies a patent extension of six months on new drugs that have been tested in the elderly; a similar incentive has greatly increased the testing of drugs in children. Without such changes, Holmes notes, “we'll continue to test therapies only in the fittest people and get information that cannot be applied to older patients.”

In the meantime, though, some researchers have designed tools that can help physicians and patients make informed decisions. Doctors such as Holmes and Balducci, who treat a lot of elderly patients, generally agree that chronological age alone is a poor indicator of how someone will respond to cancer treatment. What is more revealing, they say, is the patient's physiological age—a broad measure of health and well-being—and something called physiological reserve, which is essentially the ability to withstand stress, including the stress of surgery and chemotherapy. Doctors can best determine these attributes with a tool called a comprehensive geriatric assessment, a multifaceted inventory of the patient's strengths and weaknesses that looks at how well the body is operating. The assessment takes into account chronic diseases, medications, cognitive ability, nutritional status and social support. It also examines the patient's ability to function in the world: whether he or she needs help with what doctors call “activities of daily living” (getting out of bed, dressing, bathing, eating, toileting) and with such “instrumental activities” as managing money and medications, cooking, doing laundry and negotiating public transportation.

Much like the developmental milestones that pediatricians use to assess a toddler's health, activities of daily living involve multiple body systems working together and are therefore remarkably revealing of an older person's health—and predictive of the ability to tolerate treatment, says geriatric oncologist Arti Hurria of the City of Hope Comprehensive Cancer Center in Duarte, Calif. Unfortunately, such thorough assessment is rarely available outside of major medical centers. To address that problem, Hurria and her colleagues have developed a self-administered version that takes patients a median of just 22 minutes to complete. They have also devised and tested a tool for determining chemotherapy tolerance in older patients, published in 2011 in the Journal of Clinical Oncology. “It's 11 questions, and it's not hard to do,” says Hurria, who just completed a two-year term as president of the International Society of Geriatric Oncology. She sees it as a tool to help oncologists refine their treatment plans for elderly patients. Balducci and his colleagues at Moffitt have developed a similar tool.

The idea is to give more guidance to doctors who are otherwise forced to improvise. In elderly cancer patients like my father and aunt, who suffer from a variety of chronic health problems, physicians often modify standard treatment regimens—perhaps using two chemotherapy drugs instead of three or lowering standard dosages—in the hope that the revised treatment will work well enough. The 11-question tool leads to a score that predicts—on a scale from 0 to 100 percent—the risk of severe side effects from chemotherapy. “If the risk score is very high, you might decide, after discussion with the patient, on a less aggressive approach,” says oncologist William Tew of Memorial Sloan Kettering Cancer Center in New York City. Having a clearer idea of the patient's risk profile, he says, is especially critical when dealing with cancer that has spread from its original site in the body because such cases tend to require prolonged and arduous therapy.

Tools for predicting response also provide a framework for conversations with the patient and his or her loved ones about how much risk—and what kind of risk—they feel is appropriate. A young patient may be willing to tolerate extreme side effects and long hospitalizations for a chance to live longer. For an elderly patient, having to enter a nursing home because of side effects might seem like a fate worse than dying. Hurria and Holmes say they spend about equal amounts of time persuading octogenarian patients to consider treatment and warning them about taking on too much risk. “Sometimes we say, ‘You're actually really fit,'” Holmes says. “‘Maybe you'd like to treat the cancer as if you were a 55-year-old.'” As elderly survivors like my father can attest, having lived many years in no way disqualifies you from gunning for more time.

SCIENTIFIC AMERICAN ONLINE
Learn about Arti Hurria's 11-question scoring tool at ScientificAmerican.com/dec2014/soh