Can We Bury The Idea That Psychotherapy Increases The Survival Of Cancer Patients?

James C. Coyne, Ph.D., Michael Stefanek, Ph.D., Steven C. Palmer, Ph.D.

jcoyne@mail.med.upenn.edu

A significant proportion of breast cancer patients attending support groups do so with the belief that they may be extending their lives (Miller et al., 1998).

Can We Move Beyond the Impasse?

Claimed that 5 of 11 randomized trials demonstrate an effect of psychosocial intervention on survival time.

Evidence for a benefit to survival attributable to psychotherapy is, at best, “mixed”, (Lillquist & Abramson, 2002, p. 65), “controversial” (Schattner, 2003, p. 618) and “contradictory” (Greer, 2002, p. 238).

“A definite conclusion about whether psychosocial interventions prolong cancer survival seems premature” (Smedslund & Ringdal, 2004, p 123).

It is with a heavy heart that I have concluded that Dr. Coyne suffers from an incurable illness: narcissistic myopia. He is a depression researcher, so successful treatment of mere anxiety symptoms appears meaningless to his limited vision. It … seems to permit him to dismiss the results of 25 years of my and many other colleagues' research demonstrating positive effects of group support for cancer patients. I can live with his distortion of the published data…But when he insults my colleague Dr. Catherine Classen by referring to her as "Cathy," and worse insults my patients by informing us that our supportive/expressive groups are a "waste of seriously ill patients' potentially short remaining lives," my tolerance for his obvious impairment vanishes. One of my patients who attended our supportive/expressive group for six years said: "This group is the least superficial thing I do in my life." She and her family thanked me for it when I visited her home shortly before she died.

David Spiegel, M.D., Stanford University

Re-Evaluating the “Positive Studies”…

Three of the “positive trials” can be eliminated because in each case, patients in the intervention got substantially better medical surveillance and care.

Two of the investigator groups for these trials deny that they were even studying psychotherapy!

McCorkle R, Strumpf NE, Nuamah IF, Adler DC, Cooley ME, Jepson C, Lusk EJ, Torosian M (2000): A specialized home care intervention improves survival among older post-surgical cancer patients. J Am Geriatr Soc, 48: 1707-1713

McCorkle et al (2000)

Authors distinguish their intervention from studies examining psychosocial variables, stating, “…this is the first [study] to examine the impact of…nursing interventions on survival in cancer patients. Other studies have focused have focused on…patient’s psychosocial status, including depressive symptoms, function, and the effects of support groups” (pp. 1708).

McCorkle et al (2000)

“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” (McCorkle, personal email communication, August 3, 2004).

Kuchler T, Henne-Burns D, Rappat S, Holst K, Williams JI, Wood-Dauphinee (1999): Impact of psychotherapeutic support on gastrointestinal cancer patients undergoing surgery: Survival results of a trial. Hepato-Gastroenrerol 46:322-335

Kuchler et al (1999)

Although the length of hospital stay was approximately the same in the two groups, the intervention group received almost twice as much intensive care. Post-treatment, patients in the intervention group reported twice as much chemotherapy and three times as much “alternative treatment.”

Richardson JL, Shelton DR, Krailo M, Levine AM (1990): The effect of compliance with treatment on survival among patients with hematologic malignancies. J Clin Oncol, 8: 356-364.

Richardson et al

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.

Richardson (Personal communication, Jan 3, 2005)

Spiegel D, Bloom JR, Kraemer HC, Gottheil E (1989): Effect of treatment on the survival of patients with metastasic breast cancer. Lancet 2:888-891.

Cited 900 Times

Something Odd Occurred in the Control Group.

Of the 12 patients assigned to the control group who were still alive at 2 years, all died by one day after the four year anniversary of randomization.

inconsistent with typical survival curves for people with cancer, which are generally skewed due to a few people surviving markedly longer than the rest. Patients were on average already two years past diagnosis at randomization, so this increased rate of death occurred relatively late.

32% of locale-matched women with metastatic breast cancer would be expected to be alive between 5 and 10 years after diagnosis.

Spiegel et al.’s control patients experienced a four-year survival rate of only 2.8%.

In contrast, the four-year survival of patients randomized to intervention was 24%, substantially closer to expected value in the absence of an effective intervention and suggesting bias in the initial sampling.

There is a lack of significant differences when appropriate statistics

are used.

Spiegel et al. (1989) report that “the intervention group lived on average twice as long as did controls” (p. 889).

Given the skewness of most survival curves, median survival time is generally considered the better expression of central tendency because the median reduces the possible excessive influence of outliers.Median survival times for Spiegel et al.’s (1989) intervention and control groups were not significantly different.

Fawzy, F.I., Canada, A.L., & Fawzy, N.W. (2003). Malignant melanoma: effects of a brief, structured psychiatric intervention on survival and recurrence at 10-year follow-up. Arch Gen Psychiat 60, 100-103.*

Fawzy FI, Fawzy NW, Hyun CS, Elashoff R, Guthrie, D, Fahey JL, Morton DL (1993): Malignant melanoma. Effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years later. Arch Gen Psychiat, 50: 681-689.

*Cited Almost 500 Times

Fawzy et al. (2003) provided a provocative and seemingly compelling summary of the results for the intervention prolonging survival as assessed at six and ten year follow up:

When controlling for other risk factors, at 5- to 6-year follow-up, participation in the intervention lowered the risk of recurrence by more than 2 1/2 fold (RR = 2.66), and decreased the risk of death approximately 7-fold (RR = 6.89). At the 10-year follow-up, a decrease in risk of recurrence was no longer significant, and the risk of death was 3-fold lower (RR = 2.87) for those who participated in the intervention.

Fawzy et al. (1993) and Fawzy et al. (2003)

Inappropriate Analysis and Interpretation of Statistics

• Fawzy calculated an odds ratio, not a relative risk, and it is an inappropriate statistic for evaluating a clinical trial.

• Only 20 deaths in the entire retained sample at 5-6 years, but Fawzy had 6 control variables in his regression analysis, far below any recommended minimum ratio of ten to fifteen events per covariate The risk of spurious findings is high.

Fawzy et al. (1993) and Fawzy et al. (2003)

• Despite the dramatic way in which results for 10 year follow up were presented, a log rank test revealed no significant difference between the intervention and control group in overall survival (Fawzy et al, 2003).

• Small magnitude of difference between intervention and control group is highlighted by noting that survival differences would become non-significant with the reclassification of a single patient (Fox, 1995; Palmer & Coyne, 2004).

Fawzy et al. (1993) and Fawzy et al. (2003): A Critical Look

• Of 40 intervention patients, one was excluded after randomization due to death during the intervention, one due to incomplete baseline data, and a third due to the presence of Major Depressive Disorder.

• Of the 40 participants randomized to the control condition, only 28 produced complete baseline and 6-month data. Although lack of complete data was a reason for excluding one subject from the intervention condition, survival data were included as much as possible for those in the control condition, regardless of the completeness of their data.

Neither the Spiegel nor the Fawzy study were designed to test the effects of psychotherapy on survival.

Since then, there have been three trials designed with this goal, and none of them has yielded a positive effect.

Cunningham, A. J., Edmonds, C. V. I., Jenkins, G. P., Pollack, H., Lockwood, G. A., & Warr, D.,(1998). A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer. Psycho-Oncology, 7, 508-517. Goodwin, P. J., Leszcz, M., Ennis, M., Koopmans, J., Vincent, L., Guther, H., et al. (2001). The effect of group psychosocial support on survival in metastatic breast cancer. New England Journal of Medicine, 345, 1719-1726. Kissane, D. W., Love A., Hatton, A., Smith, G., Clarke, D. M., Miach, P., et al. (2004). Effect of cognitive-existential group therapy on survival in early-stage breast cancer Journal of Clinical Oncology, 22, 4255-4260.

No study that was designed to test whether psychotherapy improved survival and in which the intervention group did not get better medical care has demonstrated an effect.

Claim that psychotherapy promotes survival depend on the Spiegel and Fawzy studies, which have serious limitations.

Should We Attempt More Studies With Metastatic Breast Cancer Patients?

We have no credible evidence that psychotherapy promotes survival, and no compelling evidence for a mechanism that might allow an effect.

There is evidence for some mechanisms by which biomedical interventions might work, but not much success in producing new, effective biomedical interventions.

“Despite more than 3 decades of research, metastatic breast cancer (MBC) remains essentially incurable and, after documentation of metastasis, the median survival time is approximately 2 years” (Bernard-Marty, Fatima Cardoso, & Piccart, 2004, p.617).

Should We Attempt More Studies With Early Breast Cancer Patients?

In the U.S the 5-year survival rate for women with localized breast cancer is now 98% (American Cancer Society, 2006).

This high rate of survival makes it difficult to demonstrate that any additional treatment would yield a clinically significant improvement.

An integration of 28 trials of with 16,513 women of whom 3782 had died concluded that both tamoxifen and cytotoxic chemotherapy reduce five year mortality (Early Breast Cancer Trialist’s Collaborative Group, 1988). Yet, when trials were considered individually, only a single trial had an effect significant at p <.01.

Inherently Implausible?