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Hormone therapy in prostate cancer: moving into the 21st century

Created: 23/1/2006

 

Hormone therapy in prostate cancer: moving into the 21st century
Whelan, P
Eur Urol Supp. 2005 March; 4: 53-56

INTRODUCTION

  • Since introduction of PSA testing in early 1990’s there has been a significant stage shift in carcinoma of the prostate (CaP) at presentation
  • 15 years ago 50% of patients had metz
  • Currently: USA 10% have metz, Europe ˜ 10-15%
  • Immediate hormone treatment for locally advanced or localised disease remains controversial due to lack of randomised prospective clinical trials

Metastatic disease

MAXIMUM ANDROGEN BLOCKADE (MAB)

  • In general, MAB not justified for the minimal increase in survival in patients with metastatic disease as previously suggested by Labrie in the earlt 1980’s
  • May be some benefit to younger patients with small metastatic disease burdens
  • 1989/90 average response to castration was 18-24 months, after progression survival was rarely longer than 6 months
  • Current studies indicate that on average patients survive twice as long
    • Probably due to improved monitoring, use of more than 1 hormone before introduction of non-hormonal therapy
  • NB. In men in late 70’s or early 80’s with metz, average 4 year survival may equate to expected natural survival

HORMONAL THERAPIES

  • Surgical castration, anti-andrgens, LHRH androgens and oestrogens can be used sequentially and often result in a fall in PSA (after 2nd-line therapy or even 3rd –line therapy using oestrogens)
  • 2nd-line/3rd line response duration approx 12 months or more[1]

INTERMITTENT ANDROGEN BLOCKADE (IAR)

  • Intermittent hormone therapy originally described by Klotz in 1988
  • Feasibility study by EORTC:
    • Hormone therapy will reduce PSA to a nadir value in >80% of men with metz
    • An arbitrary threshold value of 20ng/ml for re-starting patients is safe (even with a heavy disease burden)

  • Off treatment duration may be up to 12 months which is of benefit to patients as far as side effects are concerned
  • As more cycles continue “off-period” shortens to the point where continual therapy is the preferred option
  • To date no evidence exists that IAR is less effective than continual therapy

LOCALLY ADVANCED PROSTATE CANCER

  • Patients with PSA’s >20, Gleason scores >7, evidence of T3 disease or bone metz are rarely considered for curative treatment (however, many with no evidence of metz will receive EBRT and some may undergo radical surgery)
  • Bolla et al[2] and RTOG[3] demonstrated that neo-adjuvent and/or adjuvant hormone treatment is better than RT alone in such patients
  • Results are awaited from MRC UK and NCI Canada as to whether RT and hormones is better than hormones alone

Does early or late hormonal therapy have an affect on outcome in locally advanced disease?

  • MRC study and EORTC (recently submitted as an abstract to AUA and EAU)
    • There is some benefit in crude survival with immediate hormones
    • NB. Balance needs to be struck between side-effects over many years and a small survival benefit……Studies into IAB in this area are required

Biochemical Failure (BF) following definitive treatment for early stage CaP

  • 1 third and possibly as many as half of patients undergoing “curative therapy” sooner or later have evidence of BF
  • Role of hormones remains controversial
  • Lack of trial data RE: immediate vs deferred hormone therapy in such patients
  • Pound et al (Johns Hopkins)[4]
    • 8 years from initial rise in PSA following radical prostatectomy to evidence of metz
    • Further average of 5 years before death from cancer
  • Prospect of hormonal therapy for this duration will cause significant side-effects
  • Need a trial using IAB, chemotherapy and novel agents to control PSA also include QOL and side-effect data

References

1. Smith, D., et al., A phase II trial of oral diethylstilbesterol as a second-line hormonal agent in advanced prostate cancer. Urology, 1998. 52(2): p. 257-260.

2. Bolla, M. and e. al, Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med, 1997. 337: p. 505-511.

3. Pilepich, M. and e. al, Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys, 2001. 50: p. 1243.

4. Pound, C., et al., Natural history of progression after PSA elevation following radical prostatectomy. JAMA, 1999. 281: p. 1591.


ArticleDate:20060123
SiteSection: Article
 
   
    
                                            



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