Letting Go of the Hope That Psychotherapy Prolongs Cancer Survival

The contribution of psychological health to the length of cancer survival has been a controversial and highly debated issue throughout the last decade. Does living better result in living longer? Two influential US randomized controlled trials (RCTs) reported by Spiegel et al in 1989 and Fawzy et al in 1993 created support for the idea that psychotherapy promotes survival. Yet both had methodological weaknesses, with small sample sizes and the lack of survival as an a priori end point at the heart of critiques. Fox compared the Stanford patients with metastatic breast cancer with the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) data, which suggested that 32% of women with metastatic breast cancer during that time would have been expected to be alive beyond 5 years, whereas only 2.8% of the controls of Spiegel et al controls and 24% of their group intervention were alive. This highlighted the inadvertent sampling bias that can emerge in small trials, despite efforts through random assignment to balance extraneous sources of group differences. Similarly, Coyne and colleagues pointed out, with respect to the Fawzy et al study, that the reclassification of a single patient would have made their survival findings nonsignificant. Analyses were not based on intention-to-treat principles. Again, for this era, the 5-year survival rate for stage I melanoma was 92%, whereas the control arm patients retained for analysis had a 5-year survival rate of only 72%. Despite these criticisms,the general public opinion about the mind being able to exert power over the body made adequately powered replication of these studies (with survival as a primary end point) mandatory. In this issue, Boesen and colleagues from the Danish Cancer Society report no survival benefit from their replication study of the psychoeducational intervention done by Fawzy et al for patients with cutaneous malignant melanoma, from which Fawzy’s group had found a survival gain persisting at 10-year follow-up. This intervention is a brief six-session, manual-based, structured program teaching health-promoting behaviors, stress management, problem-solving, and mutual support. The original University of California, Los Angeles, RCT involved a small cohort of 68, whereas the Danish replication study was better powered with 259 patients with melanoma. Only Breslow depth and lymph node status were significant prognostic factors for time to recurrence and length of survival in the Danish study. This report comes hot on the trail of other RCTs conducted as replication studies of Supportive-Expressive Group Therapy (SEGT) to examine its ability to prolong survival in women with metastatic breast cancer. Again, larger cohort sizes achieved adequate power in these replications—the Canadian multisite SEGT study, 235 women; Australia’s SEGT, 227 women; and Spiegel’s group, 125 women. Another Australian study tested the survival benefit of group therapy in a cohort of 303 women with early-stage breast cancer. All of these prospective studies failed to find survival benefits, despite reducing distress and preventing onset of new cases of depression. Might there be cross-cultural differences in the efficacy of different interventions? One always needs to allow for the adaptation of a therapy to the health beliefs and coping styles of an ethnic group. The current evidence comes from Western societies where psychological mindedness, rather than a somatic expression of distress, has developed across the past century. There is a caveat that every intervention needs to be culturally appropriate for the group to which it is applied. Nonetheless, taken together, these replication studies have been of the utmost importance to psycho-oncology in adopting the necessary scientific rigor, care with treatment integrity, intentionto-treat analyses, application of the CONSORT guidelines, adequate power, and a priori specification of survival as the primary end point. Other studies of psychosocial interventions suggesting a survival benefit have substantial methodological flaws and cannot compete with the rigor of these five recent replication studies. They provide incontrovertible evidence that such psychotherapy interventions are not able to extend survival. Where then does this leave the field? Two points are worth emphasis here: first, the impact of socioeconomic status and ethnicity, and second, the quality-of-life benefit of psychological and psychiatric treatments. Boesen and colleagues were able to compare nationally available recurrence and survival data on 137 patients who had refused to participate in their study with the 259 patients who did. To their surprise, they found a two-fold increase in morbidity in this former group, who also had lower socioeconomic status. Social inequality has long been associated with poorer access to and perseverance with anticancer treatments; Boesen et al review evidence about this in England, Wales, and Sweden. In the United States, the 5-year relative survival rate for all cancers combined is lower for African Americans (57%) than it is for whites (68%), while the death rate for African American men is 38% higher than whites and 17% higher than white women. Hispanics have higher rates of cancers associated with infection, such as cervix, liver, and stomach. Asians have high rates of liver JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 25 NUMBER 36 DECEMBER 2

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