Impact of Psychotherapeutic Support for Patients With Gastrointestinal Cancer Undergoing Surgery: 10-Year Survival Results of a Randomized Trial

Thomas Küchler

Journal of Clinical Oncology, Vol 25, No 19 (July 1), 2007: pp. 2702-2708

Psycho-oncology is currently a target of behavioral research in medicine. The effects of psychosocial interventions, although perceived by the lay community to be of benefit, remain controversial. Moreover, there is still professional debate on the most appropriate timing of the intervention (before, during, or after medical treatment), which approaches are efficacious (standardized or individualized programs: individual, family, or group treatment), and whether or not psychosocial interventions influence survival.

A recent review, covering the period from 1954 to 1999, included 329 psychosocial intervention trials, but only four of those focusing on survival showed at least fair methodology. From these studies, with follow-up ranging from 1 to 6 years and sample sizes ranging from 66 to 121 patients, no conclusions or recommendations for psychosocial interventions could be made. In the same year, Spiegel in Nature Reviews Cancer, identified five studies with potential benefit for cancer patients’ survival, as well as five studies with neutral results and provided a salient review of these trials. Although the methods differed, both reviews concluded that, despite the growing body of knowledge in this area, further research was necessary. Since 2002, there has been one additional trial. While no differences in survival were found, psychological outcomes were positive. In addition, Fawzy presented the results of their 10-year follow-up and concluded that the intervention effect was still significant for survival, but the relative risk (RR) for those who participated in the intervention (compared with those who did not) decreased compared to the original study (from RR = 6.89 to RR = 2.87).

The impact of psychotherapeutic support on survival for patients with gastrointestinal cancer undergoing surgery was studied. A randomized controlled trial was conducted in cooperation with the Departments of General Surgery and Medical Psychology, University Hospital of Hamburg, Germany, from January 1991 to January 1993. Consenting patients (N = 271) with a preliminary diagnosis of cancer of the esophagus, stomach, liver/gallbladder, pancreas, or colon/rectum were stratified by sex and randomly assigned to a control group that received standard care as provided on the surgical wards, or to an experimental group that received formal psychotherapeutic support in addition to routine care during the hospital stay. From June 2003 to December 2003, the 10-year follow-up was conducted. Survival status for all patients was determined from our own records and from three external sources: the Hamburg cancer registry, family doctors, and the general citizen registration offices.

Results: Kaplan-Meier survival curves demonstrated better survival for the experimental group than the control group. The unadjusted significance level for group differences was P = .0006 for survival to 10 years. Cox regression models that took TNM staging or the residual tumor classification and tumor site into account also found significant differences at 10 years. Secondary analyses found that differences in favor of the experimental group occurred in patients with stomach, pancreatic, primary liver, or colorectal cancer.

The focus in the psycho-oncology literature, as initiated by Spiegel  has been on studies of women with metastatic breast disease. Of the five available randomized trials, only that by Spiegel reported a significant difference in survival for women receiving a psychosocial intervention. In the literature it appears that psychotherapeutic treatment has a more positive impact on patients with leukemia, melanoma, Hodgkin's disease, non-Hodgkin's lymphoma, and (endstage) cancer of different tumor sites.

The original results of this study in terms of survival benefits for the experimental patients were somewhat surprising and had not been hypothesized. Thus, it seems useful to compare our protocol with those of the trials mentioned above to determine which aspects of our approach might be of special importance.

Different from several trials, we started our interventions preoperatively, during the diagnostic phase. Clinical experience suggests that this is the time of the greatest anxiety/uncertainty. The therapists were involved preoperatively, to deal with specific anxieties related to surgery. They helped during the first postoperative week when patients have to face two different stressors: physical impairment due to extensive surgery and psychological distress due to uncertainty about the prognosis. The therapists also assisted the patients in coping with predictable stressful events, such as communication of the histopathologic findings or the necessity of adjuvant treatment. Given the low physical and mental state, this often cumulates not just in a significant decrease of hope and confidence, but in a real personal crisis (eg, What will happen with me and my life, to my family?). Based on clinical experience, being present when things happen might be more effective than talking about such events weeks later.

Similar to the trial by Fawzy  we focused not just on active coping but on information about all aspects of surgery and oncological treatment.

The discharge interview—when the patients reviewed their time in the hospital—targeted emotional integration of the whole event. It included elements of cognitive-existential therapy as in the trials by Spiegel et al or Kissane  

The reason why only some studies of patients receiving psychotherapeutic support do better than some that do not may be related to the timing of the intervention. Perhaps expecting positive effects from psychotherapeutic treatment in patients with metastatic disease is often too late in the course of the disease to have an impact. Stress reduction, if that is the causal mechanism, may have to occur earlier, both in terms of tumor stage and intervention, to achieve positive results. The recent study by Kissane —that examined early-stage cancer with intervention that started after the medical treatment found, like most other studies of breast cancer, psychological benefits but no influence on survival—may support our suggestion.

The mechanism of early stress reduction seems to be important, since over the 2-year follow-up we found no indication that pre- and postoperative adjuvant therapies had a substantial impact on survival. The mechanisms of how this supportive approach influences better coping, more awareness toward health behaviors, and enhanced social support remain theoretical because these rather complex concepts were not measured distinctly.

Recent results of brain research have begun to identify the molecular basis of emotion, especially fear. However, one can only speculate to which extent those results may contribute to explaining the survival results of this study.If reduced, fear may influence the immune system to continue to function more efficiently, and it may have facilitated better survival in the experimental group. This conjecture, of course, remains purely hypothetical.

Limitations and Weaknesses
The strengths of this trial, its closeness to daily clinical practice, and its focus on individual patient's needs, are at the same time its weaknesses. Accruing cancer patients preoperatively did not allow for stratification by tumor site because the diagnosis was preliminary at random assignment. This led to the inclusion of 22 patients with no or benign tumors (whose exclusion did not alter the results). The individualized approach, which certainly reflects the reality of daily, psycho-oncological cancer care, makes replication trials difficult. Another limitation is the fact that we could only compare those adjuvant therapies that took place within our hospital. For the follow-up we had to rely on patients’ self-report. Nonetheless, neither the information from the charts nor that from the patients give any indication that there were meaningful differences between the groups concerning the additional treatments or that those small differences could account for the overall survival differences. However, the biggest limitation in extrapolating the results was the change in the health care system. Compared with the time of the original trial, preoperative inpatient hospital days have dropped to 1 or 2, thus reducing the opportunity for preoperative interventions, or perhaps necessitating new approaches to implementing psychosocial care preoperatively.

Conclusion: The results of this study indicate that patients with gastrointestinal cancer, who undergo surgery for stomach, pancreatic, primary liver, or colorectal cancer, benefit from a formal program of psychotherapeutic support during the inpatient hospital stay in terms of long-term survival.