Seven studies claimed to show psychotherapy extends survival of cancer patients did not

bjhpDavid Spiegel passionately promotes the idea that psychotherapy extends the survival of cancer patients. In British Journal of Health Psychology, he restates claims he previously presented in Psycho-Oncology that eight of 15 relevant trials show that cancer patients live longer with individual and group psychotherapy. The tables in the two articles are identical, with the same glaring omissions.

The issue of whether psychotherapy can promote the survival of cancer patients is important forpsycho-oncology cancer patients making decisions about treatment of their disease. So, it is important for scientific journals to make the best evidence available and to indicate when articles have not been adequately peer reviewed. Cancer patients and their care providers are desperately seeking such information. Even if filtered through media, articles in scientific journals are where much information starts and lend authority to other sources of information.

A previous blog post provided the reasons to doubt the original 1989 study by Spiegel et al. in Lancet provided evidence of psychotherapy improving the survival of women with metastatic cancer.

In this blog post, I will review the other seven studies also cited by Spiegel as positive.

In each case, the inadequacy of these studies have been discussed in the literature. Spiegel has even debated us as to their interpretation and we replied. But in nowhere in the British Journal of Health Psychology or Psycho-Oncology articles was this debate or any criticism of these studies acknowledged.

When adequately in place, peer review should ensure that claims are reconciled with the available literature, not only for professionals, but for consumers, in this case, patients. Authors are certainly free to express their opinions, but should place them within the ongoing debate within the scientific community.

Resources related to past critiques of this literature are available here: citations, abstracts, PDFs, and slide shows.

Seven studies cited as evidence of the positive effects of psychotherapy on survival of cancer patients that are not positive

Spiegel D, Butler LD, Giese-Davis J, et al: Effects of supportive-expressive group therapy on survival of patients with metastatic breast cancer – A randomized prospective trial. Cancer 110:1130-1138, 2007. Article available here.

This study attempted to replicate Spiegel’s original 1989 Lancet study. It was a negative trial finding, with no overall statistically significant effect on survival.

Spiegel counted this study as a positive finding based on post hoc subgroup analyses in which the 12 women of 25 with negative estrogen receptor status who received the intervention lived longer. I cannot imagine such a post hoc subgroup analysis of 12 patients’ exposure to a medical intervention being taken seriously—or even published.

If anything, an effect restricted to positive estrogen receptor status women is the opposite of what would have been predicted from Spiegel’s psychoneuroimmunological speculations.

Spiegel fails to note that another study of supportive expressive therapy by Kissane and colleagues attempted to replicate this finding in similar post hoc analyses and failed to do so.

Richardson JL, Shelton DR, Krailo M, et al: The effect of compliance with treatment on survival among patients with hematologic malignancies. Journal of Clinical Oncology 8:356-364, 1990. Abstract here.

This trial evaluated 3 different interventions training low income cancer patients and their caregivers to monitor side effects and complications, communicate better with medical personnel, and recognize and get prompt attention for fever, bleeding, and other medical problems.

I wrote to the first author and she replied:

“I would agree that our study was not psychotherapy. Our study was very behavioral in concept and delivery – teaching people how to manage the disease, the treatment and the health care system. I think you can go a long way with basic patient education, family education, and health care system manipulation strategies.”

Fawzy FI, Fawzy NW, Hyun CS, et al: Malignant-melanoma – effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years later. Archives of General Psychiatry 50:681-689, 1993 Article available here

This small study of stress management and health education malignant melanoma patients did not have survival as a primary endpoint nor even a provision for follow-up assessments. Nonetheless, inspired by the Spiegel 1989 Lancet study, the authors undertook a post hoc examination of survival at 5-6 and 10 years post treatment.

The report of this trial was savaged by Arnold Relman, former editor of the New England Journal of Medicine as

…fatally flawed because the analysis is not by the intent-to-treat method, which should be standard epidemiologic practice. The authors did not report the results on all their randomized subjects, which would have been the proper, “intent-to-treat” procedure. The number of exclusions and losses to follow-up after randomization could easily have affected the outcome critically since their groups were relatively small and they report a relatively small number of deaths or recurrences.… You simply cannot find out what happened to a lot of missing patients in this study, so you cannot have much confidence in the conclusions.

Wally Sampson, Editor Emeritus of the Science-Based Medicine blog caught something strange going on in the control group. The 5-year survival of Stage I melanoma at the time of the study was approximately 92%, yet the 5-year survival for patients from the control group retained for analysis was only about 72%. Sampson calculated that the probability of a representative sample of 34 persons with Stage I melanoma having a 5-year survival rate this low is about 0.001.

The report of this study claims a sevenfold difference in survival at 5-6 years and threefold at 10 years. This represents an abuse of statistics. A simple log-rank statistical test was not significant for differences in the distributions of survival for the two groups. An odds ratios is inappropriate to summarize a clinical trial and overestimate the benefits an intervention would show in clinical practice. And these odds ratios showed up only in inappropriate multivariate analyses. The authors selected possible covariates from preliminary analyses, inspecting almost as many covariates as the number of deaths to be explained (20), violating the usual rule of having at least 10 to 15 events (in this case deaths) to be explained per covariate.

Speigel does not mention that in 2007 a Danish group led by Ellen Boesen reported a failure to replicate an survival effect in a large, well designed controlled trial. Fawzy’s co-author/wife served as a consultant. No effect for survival or time to recurrence was observed.

Kuchler, T., B. Bestmann, et al. (2007). Impact of psychotherapeutic support for patients with gastrointestinal cancer undergoing surgery: 10-year survival results of a randomized trial. JCO,25(19): 2702-8. Article here.

This study claimed that 222 minutes of psychotherapy produced a 10-year improved survival among  patients with gastrointestinal cancer. The therapist took an active role in patients’ medical care, spending as much time interacting with the rest of the medical team as with the patients. Patients receiving psychotherapy also got much more postoperative chemotherapy, radiotherapy, and time in intensive care. Any effects of being assigned to psychotherapy cannot be separated from more medical care.

McCorkle R, Strumpf NE, Nuamah IF, et al: A specialized home care intervention improves survival among older post-surgical cancer patients. Journal of the American Geriatrics Society 48:1707-1713, 2000. Article available here.

The article does not concern a psychotherapeutic intervention, but a nursing intervention monitoring physical status and heading off potentially complications of surgery.

 “…this is the first [trial] to examine the impact of…nursing interventions on survival in cancer patients. Other studies have focused on patient’s psychosocial status, including depressive symptoms, function, and the effects of support groups”

I asked the first author directly about the purpose of the study and  she replied:

 “We did what we did really because of the physical care. The deaths were related to major complications, sepsis, pulmonary embolus, etc. The nurses picked these things up and prevented the crisis” (R. McCorkle, personal communication, August 3, 2004)

The primary analyses for the trial did not demonstrate an effect on survival.

Andersen BL, Yang HC, Farrar WB, et al: Psychologic Intervention Improves Survival for Breast Cancer Patients A Randomized Clinical Trial. Cancer 113:3450-3458, 2008. Article available here.

The intervention involved providing women with strategies to reduce stress and improve mood and diet.

My colleagues and I examined this trial carefully and concluded in a published critique that survival was not a primary outcome and there was a lack of indication that an effect had been achieved.

The article did not provide standard unadjusted outcomes for survival that would allow independent evaluation of claims of a positive effect. However, there was no difference between the proportion of women who died in the intervention group (21.1%) versus the control condition (26.5%). We obtained similar results when we examined only those deaths due to breast cancer. The number of differences in recurrence (n=4) and survival (n=6) between the 2 groups is less than impressive.

This was about as far as we could go in re-analyzing the data of Barbara Andersen and colleagues. When we submitted our critical commentary to Cancer, Andersen attempted to have it suppressed. When she did not succeed, she refused to offer a reply. She has since also refused to answer journalists’ questions concerning our commentary.

Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733742. Article available here.

The trial provided cancer patients at the end of life with four opportunities to discuss resuscitation preferences, pain control, and the aggressiveness of treatment. Patients in the intervention group subsequently received less aggressive treatment, were less depressed and had higher quality of life, and lived longer with a median survival advantage of 2.25 months.

There is no indication that the investigators’ primary aim was to extend life, which would be  counter to the purposes of palliative care. The most parsimonious explanation of group differences is that life was shortened in the control group because of more aggressive treatment.

Should these problems have been mentioned in the British Journal of Health Psychology and Psycho-Oncology?

These criticisms are readily available in the literature.

An author can certainly disagree with these criticisms, but in the interest of balance, should acknowledge to readers that these problems exist and provide citations so the readers can decide for themselves what they think.