Mind matters in cancer survival.

The field of psycho-oncology is hung up on the hyphen in its name. How do we understand the link between mind and body? Is that hyphen merely an arrow to the left, indicating that cancer in the body affects the mind? Can it be an arrow to the right as well, mind affecting the course of cancer? We know that social support affects survival, 1 including that with cancer.2 Also, people tend to die after rather than before their birthdays and major holidays.3,4 Depression worsens survival outcome with cancer.5,6 Yet we have been understandably delicate about mind-body influence, not wanting to claim too much, or to provide unwitting support for overstated claims that wishing away cancer or picturing white blood cells killing cancer cells would actually do it. That arrow to the right is a connection, not a superhighway. Yet in our desire to be respected members of the oncology community we have often minimized a natural ally in the battle against cancer – the patient’s physiological stress coping mechanisms. Even at the end of life, helping patients face death, make informed decisions about level of care, and controlling pain and distress is not only humane but appears to be medically more effective than simply carrying on with intensive anti-cancer treatment alone.7 A recent randomized clinical trial of palliative care for non-small cell lung cancer patients8 makes that case strongly. The authors reported a clear but apparently paradoxical finding: “Despite receiving less aggressive end-of-life care, patients in the palliative care group had significantly longer survival than those in the standard care group (median survival, 11.65 vs. 8.9 months; P=0.02)” (p. 738). Those randomized to palliative care became less depressed as well. The palliative care condition consisted of an average of 4 visits that focused on choices about resuscitation preferences, pain control, and quality of life. The study suggests that at the end of life the most aggressive treatments may not be the most effective, not only psychologically, but also medically. How could living better at the end of life lead to living longer? When we began to investigate the effects of support groups for people with cancer in the 1970’s, we and others were concerned that watching others die of the same disease would demoralize patients, and might even hasten their death. We evaluated mood and discussion content minute-by-minute to determine whether bad news about other group members was despressogenic. We found that these women with advanced breast cancer talked more seriously about death and dying, but showed no signs of depression or panic.9 Indeed our initial studies, confirmed by many others, indicated that we reduced distress and pain.10,11 But now the results are showing something more profound than reduced distress and pain or feeling better, they are showing that facing death better helps people to live longer with cancer. We reported in 1989 the results of a clinical trial demonstrating that women with metastatic breast cancer randomized to a year of weekly group therapy lived 18 months longer than control patients, and that the difference was not due to differences in initial disease severity or subsequent chemo- and radiotherapy. The result of this 10 year study, cited at last count on Google Scholar 2,222 times, was first greeted with great excitement and later skepticism. Now 21 years later, the findings are being confirmed. A decade later we conducted an IRB-approved replication study that showed no overall effect of a similar group therapy on breast cancer survival, but a significant interaction with tumor type, such that those with estrogen receptor negative cancers who were randomized to group therapy lived significantly longer than did ER negative patients receiving standard care alone.12 While this is a clear disconfirmation of the hypothesis that facing death together could improve survival, major advances in hormonal and chemotherapies had improved overall survival for women with metastatic breast cancer in the interim.13 However, women with ER negative tumors were largely excluded from the benefit of hormonal treatments, which could account for the difference in findings.13 Further support for this explanation comes from the fact that overall survival of our cohorts of women with metastatic breast cancer has improved over the decades (See Figure 1). Figure 1 Comparison of Survival across 3 Spiegel Metastatic Breast Cancer Studies More recently, a randomized trial of psychoeducational groups for women with primary breast cancer found both significantly reduced rates of relapse and longer survival. 14,15 In addition to this, our original study16, and the recent palliative care study referred to above,8 three other published randomized psychotherapy trials17–20 and one matched cohort trial21 have reported that psychosocial treatment for patients with a variety of cancers enhanced both psychological and survival outcome (See Table 1). However, six other published studies, 22–27 four involving breast cancer patients,24–27 found no survival benefit for those treated with psychotherapy. (See Table 2) Three of these six studies reported no emotional benefit from the interventions,23–25 making enhanced survival unlikely. In another major multicenter replication trial,26 Supportive-Expressive Group Psychotherapy did significantly reduce depression, but did not improve survival. However, the odd thing about this study is that the women randomized to treatment were more depressed to begin with, making their medical prognosis worse at baseline.6 Furthermore, the outcome of all of these studies is not random: no studies show that gathering cancer patients together in groups and directing their attention to emotional expression and mortality shortens survival.28 Table 1 Randomized Trials Showing Survival Benefit from Psychotherapy Table 2 Randomized Trials Showing No Survival Benefit of Psychotherapy The most provocative but also discordant results have occurred in studies of women with breast cancer, where treatment for ER positive and also human epidermal growth factor receptor 2-positive (HER2+) tumors has improved substantially. Among cancers with poorer medical prognosis, such as ER negative breast cancer, malignant melanoma, non-small cell lung cancer, leukemia, and gastrointestinal cancers, intensive emotional support seems to extend survival. Patients who benefit from a targeted and highly effective chemotherapeutic approach obtain less apparent survival benefit from emotional support than do those with less effective biomedical interventions. Thus, especially in the palliative settling in which aggressive anti-tumor treatments are less efficacious, supportive approaches become more useful. One would think that psychosocial support would have the least biomedical effect in more advanced cancers, and yet our original observation involved women with metastatic breast cancer. By the time someone dies with cancer, they usually have a kilogram of tumor in their body. Yet this may be when the body’s resources for coping with physiological as well as psychological stress matter the most.