Predictive factors of biochemical progression in prostate cancer patients treated with intermittent androgen suppression

530

529 PREDICTIVE FACTORS OF BIOCHEMICAL PROGRESSION IN PROSTATE CANCER PATIENTS TREATED WITH INTERMITTENT ANDROGEN SUPPRESSION

PRIMARY CANCER

HORMO-CHEMOTHERAPY

IN METASTATIC

PROSTATE

Van Leeuwen Astrid, Eckhardt Mardy, Boon Tom Alexandre de la Taille, Marc Zerbib, Sophie Conquy, Delphine AmaellemOuazana, Nicolas Thiounn. Thierry Flam, Djilali Saighi, Bernard Debre Urology, Cochin, Paris, France INTRODUCTION & OBJECTIVES: To define the predictive factors of intermittent androgen suppression (IAS) response in prostate cancer patients and to evaluate the feasibility of using antiandrogen alone. MATERIALS & METHODS: From 1989 to 2001, 146 patients received IAS as a primary treatment for localisedladvancedimetastatic prostate cancer (n=72) or as a treatment of PSA recurrence after radical prostatectomy (RP) and/or radiation therapy (n=74). Eighty-six patients were treated with antiandrogen alone. Androgen deprivation treatment (ADT) was continued up to 6 months after PSA became undetectable or a nadir PSA level was reached. ADT wan then re-instituted when PSA was t 4 ng/mL for patients who had RP or 2 IO nglmL for other patients. RESULTS: After a mean follow-up of 45.6 months (ranges: 5.3-196.9). 24 patients presented a biochemical progression. Overall 5-year metastatic disease free survival of 91.3%. Overall 5-year biochemical recurrence free survival was 68.1%. No difference was observed between patients treated with antiandrogen alone, antiandrogen and LHRH agonist or LHRH agonist alone. Using multivariate analysis. Gleason score greater or equal to 8 (p=O.O2 I), first phase duration without treatment 5 I2 months (p=O.O44). Positive lymph node or metastatic disease status at the time of IAS start (p=O.O23) and age 570 years were the strongest predictors of biochemical progression. For patients treated with antiandrogen alone, mean cycle duration was 14 months. Patients received from I to 8 treatment cycles (median 2) with 50.4% of the time without therapy. 5.year biochemical progression free survival was 60.9”. CONCLUSION: The best candidates for IAS seem to be the patients with age >70 years. localised prostate cancer and Gleason 5 7. Secondly, using antiandrogen alone appears to be feasible and represents a therapeutic option in selected patients with prostate cancer. Randomised prospective studies are needed to validate this new therapeutic approach.

Department

of Urology, University

Medical Center. Utrecht. The Netherlands

INTRODUCTION & OBJECTIVES: The aim of this study is to see if patients with prostate cancer and metastasis of the bone with poor prognostic factors, have a prolonged progression-free period and a longer survival with early started combined hormonal and cytostatic therapy (orchiectomy plus a high dosage of estramustin=O+E) in comparison with orchiectomy (0) alone. Some combined hormochemotherapy studies have shown some improvement in time to progression but not in survival. MATERIAL & METHODS: A multicenter study in 17 urologic clinics in The Netherlands was performed from August 1993 till September 2000. The inclusion criteria were histologically proven prostate cancer and metastasis of the bone, with 3 out of 5 criteria of poor prognosis (G2-G3, performance, pain, PSA, AF). The patients were randomised to either 0 or O+E group. In the O+E group the medication was started the day after orchiectomy. The dose was 840 mg daily for the first month and then 560 mg daily until progression or unacceptable toxicity. The follow-up schedule consisted of control visits at 2 week\, 4 weeks, 3 months and every 3 months thereafter. All patients were followed to death or to September 2000. RESULTS: Of the 85 patients randomised, 5 did not meet the inclusion criteria and I2 were protocol violations. The total number of patients recruited was 35 in the 0 group and 33 in the O+E group. The demographics of the patients were similar. Adverse events accounted for 10 withdrawals in the O+E group. Death from causes other than prostate cancer accounted for 4 withdrawals in the 0 group and 6 in the O+E group. At the end of study, 90% of the 0 group was in progression with a median time of I8 months. Of the O+E group 82% was in progression with a median time of I I months. Of the 0 group, 94% died from prostate cancer with a median time to death of 27 months. Of the O+E group 88% died from prostate cancer, with a median time of I6 months. CONCLUSION: progression-free

Primary hormo-chemotherapy period and no survival benefit.

showed

no

prolonged

532

531 PHASE III STUDY OF INTERMITTENT MAB INTERNATIONAL COOPERATIVE Calais Fernando”. Kirkali

Bono

Ziya’.Robertwn

Aldoi, Chris’

Whclnn

Peter”.

MAB VERSUS STUDY Queimadelos

CONTINUOUS

Marque\‘.

Portillo

Jr&.

‘Urt~logy. DokuL Eylul Umveraity. Ilmir, Turkey. ‘Urology. Hospital Univenity Marques de Valdecilla, Santander, Spain, ‘Urology. Policlinico La Rosadela. Santiago dc Compostela, Spain. ‘Urology, St. James University Hapital. Leeds, United Kingdom. Ylrology. Ospedale Di Circolo e Fondazione ES. Varehe, Italy. “Urology, Hospital do Dcwx-ro, Ll\hon. Portugal, ‘Urology. European Imtitute of Oncology, Milan. Italy

INTRODUCTION

& OBJECTIVES: Patients with locally advanced or metastatic prostate cancer cannot he cured with any of the therapeutic tools available today. Hence quality of life IS the mo\t important outcome, if wrvival i!, not compromised. MATERIALS

& METHODS: The South European Uro-oncological Group (SEUG) launched a phase III trial mtermittent MAB versus continuou\ MAB. The inclusion criteria were histolwical woven PCs T3-T4MO and Ml oatients. WHO O-2. aeci85. txeviouslv untreated. Afi pa&s were registered and treated with CPA 200 mg for 2-weeks and then ; monthly depot mjectmn of LHRA analogue (decapeptyl) plus 200 mg of CPAdaily. After 3 months of therapy if PSA wa below 4 or XOcl below the Initial value. patient\ were randomlxd RESULTS: Of 765 patients registered 626 have been randomised (314 in the intermittent arm and 312 m the continuous arm). At randomisation 23.7% of patient’s randomlwd have PSA m excess of 4 ng and the other\ 76 3%) have a PSA<4. The prelimmary rewlts thou that m the intermxtent arm SO%~of of the mtermittent arm are off therapy for at Ieat 49 week\ following the initial LHRH+CPA therapy. and 25% for over 3 years. Those who remain off therapy tend to have lwer PSA at the randomization. Patients with PSA less than 2 ng/ml at randomiaation have a median of 74 weeks off therapy. Intermittent patients who go hack on therapy stay on therapy for a medium time of IX week\. Side effects arc low and the mwt common are hot llwhes reported in 8.6% of the patient\. Overall Quality of Life wore\ are the ame in the two arms of the study at wxe\\ive follow-up\. At rsgiwatmn 50% of the patient\ were sexually actne in the preview month. In the contmuow arm wxual actlvlty diminr\he\ and only 25’% of patients report any \cxual activity in the last month at IS months. Sexual actwty 1s greater m the Intermittent arm with 40% of men reporting sexual activity at IS month\. Among those who arc xxually active difficulty uith crectmn\ i\ le\$ and enjoyment of \ex is greater among those on lntermittcnt thcrap). erpecially when off therapy For a median follow-up of 48 months 306 patient\ out of 626 randomiwd have gone off study, 162 in intermittent and I44 in the continuou. 57 patient\ in intermittent and 39 continuous have gone off study for wbjective progreGon. 72 patient\ in intermittent and 50 m continuous hare gone off study for wbJective or ohjrctive progrewion. 72 patient\ in the intermittent arm and 69 in the continuous arm have died.

patient\

RADICAL PROSTATECTOMY IN PATIENTS WITH LOCOREGIONAL LYMPH NODE METASTASES: RATIONALE FOR ADJUVANT ANDROGEN DEPRIVATION Heidenreich

Axel, von Knobloch

Rolf, Varga Zoltan, Hofmann Rainer

Department

of Urology. Phillips-University,

Marburg, Germany

INTRODUCTION & OBJECTIVES: The role of radical retropubic prostatectomy (RRP) in patients with locoregional lymph node metastases is still discussed controversially since no cure can be achieved by RRP alone. Recent studies. however. suggest a benefit of RRP combined with androgen deprivation (AD) with regard to recurrence rates, local complications and survival. The purpose of the study is to evaluate the therapeutic long-term efficacy of RRP combined with AD in 92 patients with positive lymph nodes. PATIENTS & METHODS: Between 111990 and 812001 855 pts underwent RRP with locoregional lymphadenectomy. All pts with N+ underwent immediate adjuvant AD either by subcapsular orchiectomy of by LHRH-analogues. Patient’s charts were reviewed for preop. PSA, pTN-stage & Gleason score of the prostatectomy specimen. A questionnaire was mailed to pts for evaluation of recurrences, mortality, and continence, quality-of-life (EORTC QLQ30).

RESULTS: 921855 pta (10.8%) demonstrated positive lymph nodes (LN) at time of RRP. 51192 pts (55.4%) had l-2 pos LN, 32192 (34.8%‘) had 3 ~05. LN and 9192 pts (9.8%) had >3 pos. LN 72192 pts (78%) underwent orchiectomy and 20 pts (22%) received LHRH-analogues. Mean follow-up is 80 (2.136) months: XX% of the pts are alive. 73% have no PSA-recurrences. PSA recurrences and mortality were only observed in pts with zpositive lymph nodes. Urinary continence and quality-of-life judged by the patients is excellent with 86% requiring 2 pads/day.

CONCLUSIONS: RRP in combination with AD appears to represent a viable option in patients with minimal locoregional lymph node metastases. Prerequisites are 1) anatomically adequate pelvic lymphadcnectomy, 2) surgical experience resulting in good functional results, 4) 13 positive lymph nodes. 5) adjuvant AD. and 6) thorough preoperative information about therapeutic alternatives. European

Urology

Supplements

1 (2002) No. 1, pp. 135