Sue Ryder Care Spring Lecture:

Do Psychological Factors

Influence Cancer Progression?

Alex Mitchell alex.mitchell@leicspart.nhs.uk

• Introduction – Psychological Factors =>Physical Outcomes (not QoL)

• I - Psychological Outlook (Observational Studies)Coping Styles Studies? Psychiatric influences

• II - Psychological Interventions (RCTs)Individual SessionsGroup

• Signif Heterogeneity

Different measuresDifferent cancersDifferent follow-up periodsDifferent outcome measuresDifferent control for physical factors

* Different stages of disease *

Psychological Measures!Psychological Measures!

SCQ

CANTRIL

PSI

LS

PAIS

SADS

LCBDISTAI

HLCSRSSPSE

TSCSHDRSEO

RSEVULHAS

JFSBOSMAACL

SHSSCL90POMS

+10

Seve

rity

0

Uncertainty / Appraisal

Depression & Irritability

Anxiety / Intrusions

Time (weeks-months after “bad-news”)

• Psychological Outlook (Changeable)Optimism vs pessimism

• Psychological WellbeingAdjustment and distressLow mood and Depression

HopelessnessWorry and Anxiety

Pre-occupationAnger, Hostility and Irritability

• Psychological Traits (Stable)Coping style (simple)

Fighting spirit, Denial (avoidance), Fatalism, Active Coping, Locus of Control

Coping Resources (complex)Problem solving ability, Participation, search for meaning / for information

Emotional

Unstable

Non-Emotional

Internal External

Stable

• For Mind-Body Link

• Psychological factors are strong

• Psychological factors can be modified

• Against Mind-Body Link

• Psychological factors are not strong

• Concentration on physical factors

Neither hypothesis supports the notion that patients should be blamed for not thinking positively !

BMJ (2002) - Influence of psychological coping on survival and recurrence in people with cancer- systematic review

BMJ 2002;325:1066

• Garssen B. (2004) Psychological factors and cancer development after 30 years of research

Clinical Psychology Review 24: 315

• The Evidence

Greer (1979) Early Br Ca n = 69

Funch (1983) Early Br Ca n = 203Diclemente (1985) Early Melanoma n=117Dean & Surtees (1989) Early breast Ca n =122

Watson et al (1999) Early breast Ca n=578Reynolds et al (2000) Early & Late Breast Ca n=847

IPOS Studies in Poster Format

Pivotal Greer (1979) StudyPivotal Greer (1979) Study +Ve Result

• Sample69 women with non-metastatic breast cancer

• VariablesDenial, stoic acceptance, helplessness/hopeless3, 6 and 12 months

• Outcome5 , 10 and 15 years

• ResultsAll factors linked with risk of death (RR x4) [CI 1.1 – 17]Fighting spirit may be protective

Greer S et al (1979) Psychological response to cancer: effect onoutcome. Lancet ii: 785-789

Funch Study (1983)Funch Study (1983) +Ve Result

• Sample208 women with early breast cancer

• VariablesSingle assessment

• Outcome20 years

• Biological Confounders?

• ResultsPsychological factors and social isolation assoc with death

Funch DP & Marshall J (1983) Role of stress, social support and age in survival from breast cancer. J Psychosom Res 27(1): 77-83

Diclemente (1985) StudyDiclemente (1985) Study +Ve Result

• Sample117 malignant melanoma patients (86% early)

• VariablesSingle assessment

• OutcomeProspective 29 months (2.5 years)

• Biological Confounders?? Tissue stage

• ResultsPoor psychological adjustment linked with relapse

Declimente RJ and Temoshok L (1985) Psychological adjustment to having cutaneous malignant melanoma is a predictor of follow up. Psychosom Med 47:

Dean and Surtees Study (1989)Dean and Surtees Study (1989) +Ve Result

• Sample121 women with non-metastatic breast cancer

• VariablesDenial, fighting spirit, stoic accept, helplessness

• Outcome8 years after mastectomy

• Biological ConfoundersTumour size and node status

• ResultsThose with denial survived longer than those with stoic accept. Or

helplessness

Dean C, Surtees P. (1989) Do psychological factors predict survival in breast cancer. J Psychosom Res 33: 561-569

Watson et al Study (1999)Watson et al Study (1999) +Ve Result

• Sample578 women with early breast cancer

• VariablesHADS, MAC, Courtauld Emotional Control (CEC)At 12 weeks & 12 months

• Outcome5 years (30% had died or relapsed)

• Biological ConfoundersTumour size and node status, treatment

• ResultsMAC Helplessness/hopelessness linked with event free survivalStrongest effect HADS depression (Hazard 3.6) after adjust.Modest effect for HADS anxietyNo beneficial effect for “positive thinking” ie fighting spirit

Watson M et al (1999) Influence of psychological response on survival in breast cancer: a population-based cohort study. Lancet 354: 1331

Reynolds Study (2000)Reynolds Study (2000) +Ve Result

• Sample847 NCI’s Black/White Cancer Survival Study Early + Late Br Ca

• VariablesFolkman and Lazarus Ways of Coping QQWithin 3 months of diagnosis

• Outcome8 years, Prospective

• Biological ConfoundersAge race tumour state, hormone response, comorbidity

• ResultsEmotional expression + perceived social support (additive effect)Effect more pronounced in EARLY disease4 x risk of dying during follow up if low expressive coping + low SS

Reynolds P et al (2000) Use of coping strategies and breast cancer survival: results from the black/white cancer survival study. Am J Epidem 152 (10): 940

Studies in Press IPOS 2004Studies in Press IPOS 2004 +Ve Result

• The Latest Research

IPOS 2004.dk Psycho-Oncology (Aug 04)

Groenvold M et al (in press)Groenvold M et al (in press) +Ve Result

Groenvold et al (2004) Level of psychological distress in newly diagnosed breast cancer patients predicts survival 7th IPOS

• Sample1582 Danish Early Breast Cancer Patients

• VariablesHADS, EORTC QLQ at 2 months after surgery

• OutcomeMean follow-up 6.7 years

• Biological ConfoundersClinical and histo-pathological risk factors

• ResultsLow distress linked with increased survival + non-recurrence

Same was shown for QoL + low fatigue, after adjustment

• Who? Cancer Nurse Specialists / Counsellors / Psychologists / Psychiatrists?

• WhatCounselling / Support, Education CBT, IPT, Group

• WhenEarly, late, self-help

• How?Participation with patient / Informing patient

• Rehse, Pukrop, 2002• Patient Educ Counselling

• Meta analysis of 37 published controlled outcome studies

EducationSupportCopingPsychotherapy

NICE P+S Care“Psychological support services”21 Grade I studies

Group Therapy and Physical OutcomeGroup Therapy and Physical Outcome

• Spiegel StudySpiegel D, Bloom JR, Kraemer HC, Gottheil E. Effect of

psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 1989, 2, 888-891.

• Fawzy StudyFawzy FI, Fawzy N et al. Malignant melanoma Effects of an early

structure psychiatric intervention on recurrence and survival 6 years later. Arch Gen Psychiatr 1993, 50: 681

• Edelman StudyEdelman S, Bell DR, Kidman AD. A group cognitive behaviour

therapy programme with metastatic breast cancer patients. Psycho-Oncology 1999 8 (4): 295-305.

• Goodwin StudyGoodwin PJ. The effect of group psychosocial support on survival

in metastatic breast cancer. N Engl J Med, 2001 Vol. 345, No. 24, 1719-1726.

Spiegel Study (1989) - MethodsSpiegel Study (1989) - Methods

• Sample86 women with metastatic breast cancer

• InterventionGroup intervention over 1 year

• Outcome10 year follow up (only 3 patients were alive)

• Biological ConfoundersCancer initial staging

• ResultsThose in the group lived 18months longer on averagePsychological predictors at baseline did not predict survival

• CitationSpiegel D, Bloom JR, Kraemer HC, Gottheil E. Effect of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 1989, 2, 888-891.

Spiegel ResultsSpiegel Results

Fawzy Study (1993) - MethodsFawzy Study (1993) - Methods

• Sample68 patients with malignant melanoma

• Intervention6 x weekly sessions for 90mins

• Outcome6 years

• Biological ConfoundersAge, initial Breslow depth, sex and site, Natural Killer Activity

• Results10/34 controls died vs 3/34 in group (p<0.03)Low baseline distress and increase in active coping => survivalLow NKCA at baseline linked with recurrence but not in MVA

• CitationFawzy FI, Cousins N, Fawzy N et al. A structured psychiatric intervention

for cancer patients I. Changes over time in methods of coping and affective disturbance. Arch Gen Psychiatr 1990, 47, 720-735.

Edelman Study (1999) - MethodsEdelman Study (1999) - Methods

• Sample124 women with metastatic breast cancer from Sydney, AU

• InterventionGroup Intervention (CBT) 8x weekly and 3x monthly

• Outcome5 year outcome

• Biological ConfoundersECOG, mets, chemotherapy

• ResultsImmediate effect on mood and self-esteem not sustain, no survival effect

• CitationEdelman S, Bell DR, Kidman AD.A group cognitive behaviour therapy programme with metastatic breast cancer patients. Psycho-Oncology 1999 8 (4): 295-305.

Goodwin Study (2001) - MethodsGoodwin Study (2001) - Methods

• Sample235 women with metastatic breast cancer from Mount Sinai Hospital

• InterventionGroup Intervention (Supportive-Expressive) + educational material

• OutcomeMean survival time 17.9 vs 17.6 months

• Biological Confounders?? progesterone receptors (sig) estrogen receptors (ns), time to rand,

age, nodal stage (ns), use of adjuvant chemotherapy (ns)• Results

Improvement in distress and pain, NOT survival• Citation

Goodwin PJ. The effect of group psychosocial support on survival in metastatic breast cancer. N Engl J Med, 2001 Vol. 345, No. 24, 1719-1726.

Goodwin ResultsGoodwin Results

Two Meta-Analyses

Two Meta-Analyses

• Depression (or anxiety) influencing outcome of physical disease is consistent

• Effects are likely to be modest cf tissue factors• Good studies are required to detect small effects• Effects have a greater impact in early cancer (river

analogy)• Denial is complex• Lack of emotional expression is probably hazardous• Psychological interventions definitely help wellbeing• Psychological intervention MAY NOT help survival