1. Predicting Subsequent Response to Hormone Therapy Following First-line Androgen Deprivation in Advanced Prostate Cancer
S. Turner H. Gurney V. Gebski
M. Helmer
J. Pohlan
M. Cardimone
H. Woo
M. Drummond
A. Brooks
Urological Cancer Organisation

2. The problem 80-90% response rates to first-line AD
15-30% second-line response (includes anti-androgen withdrawal)
all prostate cancers become ‘hormone refractory’
increasing options for systemic therapy
limited information about likelihood of subsequent hormone response
Fujikawa et al : 22 patients on flutamide as second-line; bCR on first-line predicted for CR on 2nd line
European Urology. 37(2): , 2000

3. Androgen Independence
androgen receptors
AR gene amplification
‘promiscuous’ AR
up-regulation of AR expression
regulation of apoptosis
EGFR  endothelin
caspases  HSPs
IGF-I  IAPs
Hengartner M.O. Nature 407: 770, 2000

4. Study objectives
to identify clinical parameters that predict for subsequent response to hormone manipulation
to develop a simple clinical algorithm for management following first-line hormones

5. Patients and eligibility
108 men with proven prostate cancer
41 (39%) initial radical treatment
managed through a multidisciplinary prostate cancer clinic
PSA response to first-line androgen deprivation
at least one trial of further hormone therapy
regular PSAs available

6. Methods and definitions
data collected retrospectively
PSA ‘response’: > 50% fall from baseline
‘complete response’: PSA < 4ng/ml
PSA progression: PSA rise triggering change in therapy
multivariate logistic regression analysis of possible predictive factors

7. Potential predictors of subsequent response
clinical features at presentation
PSA
Gleason score
demonstrated metastatic disease
‘curative’ management
features of first-line therapy
type of hormone therapy
duration, rapidity and ‘completeness’
of response

8. Results: features of first-line therapy
type of hormone therapy %
median duration of response months ( )
MAB 14.3 months ( )
castration 18.8 months ( )

9. Results: subsequent hormone response
up to 4 successive responses
9 non-responders to second-line responded to third line included in ‘subsequent responders’
overall response rate 44%
RR to AA withdrawal 53%
median duration of response 7.8 months
(range months)

10. Type of second-line hormone therapy%

11. Predictors of subsequent response

12. Predictors of subsequent response

13. Duration of response: first-line versus subsequent hormone therapy
Duration second-line (months)
Duration first-line (months)

14. Algorithm for management following first-line hormones
response < 4/12?
yes no
MAB 1st line?
MAB 1st line?
EBRT as
required
yes
yes no no
withdraw AA
symptomatic?
withdraw AA
add AA
progression?
yes no
progression?
bone pain only?
observe or experimental
yes no
chemotherapy or experimental
Sr-89, Sm-153

15. Conclusions antiandrogen withdrawal is a common event
men are less likely to exhibit a useful further response if: (a) slow response to first-line
(b) single agent employed initially
recommend this group be observed closely in order to initiate alternative therapies in timely manner