Hormonal therapy and Cognitive Function

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Hormonal therapy and Cognitive Function
Raj Persad FRCS
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Issues

• Increasing frequency of PCa diagnoses
• Younger patients
• Longer duration of therapy
• ?adverse cognitive effects

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PHYSICAL CAPACITY AT 12 MONTHS FAVOURS
BICALUTAMIDE 150MG
Favours castration
Favours Casodex 150 mg
Physical capacity
p0.046
Emotional well being
Sexual interest
p0.029
Vitality
Social function
Pain
Activity limitation
Bed disability
Overall health
-2
-1
1
2
3
4
5
0
Treatment effect and 95 2-sided CI
Iversen et al J.Urol 2000 164 1579-1582
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Early Non-metastatic PCa

• Endocrine therapy too early in the course of
  the disease is at best of no value - and maybe
  even harmful

pi05
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• For
• Survival, QoL, urinary function, pain
• Cassileth, Qual. Life Res., 19921323
• Against
• poorer emotional, physical and sexual function
• hot flushes and fatigue
• Herr, J Urol 2000.1631743

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Early vs Deferred Endocrine Therapy Survival
Difference ?
MRC-study, Messing-study, Bolla-trial, RTOG
85-31, Granfors-study, EPC data,
Gain
Loss
Endocrine therapy per se?

Tumor Burden
PSA T-1/2 pT3 cT-3/4 N
M-1
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• Sparse evidence exists on which to draw concs.
• LHRH analogues in women ? 6-56 memory decline
  reported (verbal memory and capacity for new
  learning)
• Reversed by oestrogens
• In men link between falling testosterone levels
  and neuropyschological function (visual memory
  and visual-spatial performance) reversed by
  androgens

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• Androgens have an effect on brain development
• prenatally
• Oestrogens Androgens have different effects in
  adult brain (verbal and visual-spatial functions
  respectively).
• Suppression of either will give selective defects

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How can we measure cognitive effects

• A highly specialised area of clinical psychology
• Battery of tests assesses broad areas of
  cognitive function
• Tasks
• Auditory/verbal memory
• Visual memory
• Working memory and attention
• Processing speed
• Intelligence

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• Intelligence gauged from Nat. Adult Reading
  Test. The no. of errors is used to predict full
  scale IQ
• Verbal ability using verbal fluency task
• Verbal Memory using the Rey Auditory-Verbal
  Learning Test
• Visual memory using Complex Figure Task
• Visual-spatial memory using spatial pairing of
  2D figures
• Working memory capacity using two Wechsler
  Memory Scale
• III tasks
• Processing speed using the Kendrick assessment
  of cognitive ageing

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Results to date

• Jenkins et al, BJUI 2005, 96 48-53. LHRHa for 6
  months
• Significant cognitive decline on at least one
  task in 47 patients vs 17 controls. Most were
  related to tasks of spatial memory and ability.
• Green et al, BJUI 2002, 90427-432. 77 men
  randomised to CPA, Lupron, Zoladex or
  surveillance
• Patients had decline in tasks requiring complex
  information processing vs controls

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Results (cont.)

• Cherrier et al, JUrol 2003, 1701808-11. 9 months
  of androgen deprivation.
• 50 of patients showed clinically significant
  decline in 7 of 8 tasks (unfortunately recording
  of control group decline not recorded accurately)
• Finnish study Salminen et al, Br J Cancer 2003,
  89971-6. Patients received LHRHa for 12 months
• Actually showed improvement but cog. defects
  already noted at baseline and progress could not
  be compared with controls who were only recorded
  at baseline

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Problems

• Many studies use different tests some not
  validated
• Some tests assess overlapping areas of cognition
• Difficult to control for variables of age and
  intelligence (ie in some tasks older pt may have
  poorer function from the outset)

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Summary

• Cognitive effects difficult and time consuming to
  measure
• In men decline in visual memory and
  visual-spatial performance are main areas of
  decline noted to date
• Task performance not necessarily related to T
  level
• Potential benefit of NSAA over LHRHa

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Can we avoid or prevent cognitive effects?

• Dont get prostate cancer
• Dont get advanced disease with need for
  long-term hormonal therapy
• Consider Intermittent therapy if ADT necessary
• Consider ?NSAAs preferrable
• If long-term ADT, consider risks/benefits with
  fully informed patient as with other potential
  harms of long term ADT