776 POOLED ANALYSIS OF TWO PROTOCOLS OF INTERMITTENT HORMONAL THERAPY IN ADVANCED PROSTATIC CANCER

776 POOLED ANALYSIS OF TWO PROTOCOLS OF INTERMITTENT HORMONAL THERAPY IN ADVANCED PROSTATIC CANCER

Vol. 187, No. 4S, Supplement, Monday, May 21, 2012 THE JOURNAL OF UROLOGY姞 775 INTERMITTENT ANDROGEN DEPRIVATION THERAPY: DURATION OF THE FIRST OFF ...

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Vol. 187, No. 4S, Supplement, Monday, May 21, 2012

THE JOURNAL OF UROLOGY姞

775 INTERMITTENT ANDROGEN DEPRIVATION THERAPY: DURATION OF THE FIRST OFF TREATMENT INTERVAL AS A PREDICTOR OF DISEASE PROGRESSION AND PROSTATE CANCER DEATH. Rafael Sanchez-Salas*, Dominique Prapotnich, Paris, France; Fernando Secin, Buenos Aires, Argentina; Marc Galiano, Francois Rozet, Eric Barret, Xavier Cathelineau, Paris, France INTRODUCTION AND OBJECTIVES: To analyze the association between duration of first OFF treatment interval and time to cancer specific death in prostate cancer patients who experienced biochemical recurrence (BCR) after radical prostatectomy, or radiation therapyand were treated with intermittent androgen deprivation (IAD) therapy. METHODS: We identified 158 patients who were treated with IAD therapy after BCR following prostatectomy, or external beam radiation treatment at our institution between 1992 and 2011. Ontreatment period (ONTP) consisted of three-monthly injections of gonadatropin-releasing hormone (GnRH) agonist combined with daily oral androgen receptor antagonist. Off-treatment period (OFTP) was indicated when PSA was ⬍ 4 ng/ml. Criteria for resumption of hormonal therapy were PSA ⬎20 ng/ml or clinical symptoms. Kaplan Meier curves with Uni and multivariate Cox regression model was used to identify variables associated with cancer specific survival. RESULTS: Median (Percentile 25-75) age was 65 years (6169). 110 patients were primarily treated with prostatectomy, 20 of these received salvage radiation therapy; 48 were initially treated with external beam radiation. Gleason score was ⬍6 in 75 patients (47.4%), 7 in 61(38.6%) and 8 in 22 (13.9%) men. Median PSA at initial IAD was 9.8 ng/ml (5-20). Median duration of the first off treatment interval was 46 months (27-74) Median time from local treatment to start of IAD was 29.2 months (Range: 2-52). During a median follow-up of 7.2 years (5-10) since start of IAD, 50 patients died of disease and 18 patients died of other cause. 10-year cancer specific survival since start of IAD was 57% (95%CI: 46-66) and the corresponding overall survival was 48% (38-57) After adjusting for primary therapy, age and serum PSA at the start of IAD, presence of Gleason score 8-10, and shorter duration of the first off treatment interval after start of IAD were significantly associated with worse cancer specific survival. CONCLUSIONS: Shorter duration of first OFF treatment interval after start of IAD and higher Gleason score were significantly associated with worse cancer specific survival in prostate cancer patients who experienced BCR after radical prostatectomy or external beam radiation therapy.

Variable Prostatectomy alone

HR (Reference)

P value

e317

for the treatment of advanced prostate cancer. We present pooled results from two randomized trials which used similar protocols. The objective is to compare overall and cause specific survival in patients receiving intermittent therapy compared to those receiving continuous therapy. METHODS: In MAB 626 patients mean age 73, were randomized 314 to continuous therapy and 312 to intermittent.In CAB 917 patients mean age 72 have been randomized 462 to Intermittent therapy and 455 to Continuous.The statistical analysis is through a pooled individual level meta analysis with interaction tests to assess the constancy of treatment comparisons across studies. In both protocols patients received cyproterone acetate (CPA) 200 mg for two weeks and then monthly depot injections of a LHRH analogue plus 200 mg of CPA daily during three months, induction period. In both protocols patients randomised to the continuous arm received the same treatment.MAB patients in the intermittent arm when they are on treatment received the same scheme, while in the CAB protocol, when on treatment received ciproterone acetate(CPA)300 mg/daily. RESULTS: A total of 477 patients are known to have died in the MAB study and 436 in the CAB study. There was no evidence that the effect of intermittent therapy was different in the two studies, p ⫽ 0.25 and pooling the data is appropriate. There is no difference in overall survival, adjusting for study as the death rate in CAB is lower than in MAB, p ⫽ 0.0.77, with hazard ratio (HR)0.98 95% CI 0.86 to 1.12).In MAB 56% of deaths were due to cancer and 27% due to CVD while in CAB 36% of deaths were cancer deaths and 46% CVD. In both studies there are fewer CVD deaths in the intermittent arm HR ⫽ 0.83 (95% CI 0.66, 1.05), p⫽ 0.12. While in MAB, in particular, there are more cancer deaths in the intermittent arm HR ⫽ 1.29 (95% CI 0.97, 1.72), p⫽0.09 but not in CAB, HR ⫽ 0.98 (95% CI 0.71, 1.35).There is no statistical evidence of differential effects in the two studies with regard to CVD (p⫽0.92) and cancer deaths (p⫽0.20). There was no difference in sexual activity at randomization, but after randomization, sexual activity is better in the intermittent group. CONCLUSIONS: Intermittent therapy should be considered for use in routine practice since it is associated with no reduction in survival, no clinically meanigful impairment in quality of life, better sexual activity and considerable economic benefit to individual and community. Source of Funding: None

Prostate Cancer: Basic Research IV

(95% Conf. Interv.)

Moderated Poster

Prostatectomy⫹Radiation

1.7

0.3

0.7

4.2

Radiation

1.9

0.06

0.97

3.6

Age

0.96

0.1

0.91

1.01

PSA at start of IAD

1.01

0.3

0.99

1.02

Gleason 8-10

2.24

0.01

1.2

4.3

Duration of first OFF treatment

0.99

0.008

0.978

0.997

Source of Funding: None

776 POOLED ANALYSIS OF TWO PROTOCOLS OF INTERMITTENT HORMONAL THERAPY IN ADVANCED PROSTATIC CANCER Fernando M. Calais da Silva*, Lisbon, Portugal; Maurizio Brausi, Modena, Italy; Frederico Gonc¸alves, Bratislawa, Slovakia; Jan Kliment, Martin, Slovakia; Antonio Queimadelos, Santiago Compostela, Spain; Fernando E. Calais da Silva, Lisbon, Portugal; Chris Robertson, Glasgow, United Kingdom INTRODUCTION AND OBJECTIVES: Few randomised studies have compared intermittent hormonal therapy with continuous therapy

Monday, May 21, 2012

8:00 AM-10:00 AM

777 CRUCIAL ROLE OF DICKKOPF-3 IN PROSTATE MORPHOGENESIS IN VITRO AND IN VIVO Yoshiaki Kawano*, Kumamoto, Japan; Diana Romero, London, United Kingdom; Nora Bengoa, Bilbao, Spain; Nicole Maltry, Heidelberg, Germany; Marjorie Walker, London, United Kingdom; Masatoshi Eto, Kumamoto, Japan; Jonathan Waxman, London, United Kingdom; Christof Niehrs, Heidelberg, Germany; Robert Kypta, London, United Kingdom INTRODUCTION AND OBJECTIVES: To investigate how the tumour suppressor Dickkopf-3 contributes to prostate cancer formation in vitro and in vivo. METHODS: RWPE-1 cells were stably transfected with either Dkk-3-targeting pSM2-shRNAmir (RWPE-1/D3-sh cells) or non-targeting vector (RWPE-1/NS-sh) . For 3D acinar morphogenesis assays, either RWPE-1/NS-sh or RWPE-1/D3-sh cells were plated on a thinlayered bed of Matrigel (BD Biosciences) on 8-chamber glass slides