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IS THE DEGREE OF PSA DECLINE AFTER IMMEDIATE ANDROGEN DEPRIVATION A PROGNOSTIC FACTOR FOR OUTCOME IN PATIENTS WITH T0-4 N0 M0 PROSTATE CANCER NOT SUITABLE FOR LOCAL TREATMENT WITH CURATIVE INTENT? (RESULTS FROM THE EORTC 30891 TRIAL)
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MEN WITH POOR-PROGNOSIS NON-METASTATIC PROSTATE CANCER CAN BE CURED WITH ADJUVANT ANDROGEN DEPRIVATION THERAPY
IS THE DEGREE OF PSA DECLINE AFTER IMMEDIATE ANDROGEN DEPRIVATION A PROGNOSTIC FACTOR FOR OUTCOME IN PATIENTS WITH T0-4 N0 M0 PROSTATE CANCER NOT SUITABLE FOR LOCAL TREATMENT WITH CURATIVE INTENT? (RESULTS FROM THE EORTC 30891 TRIAL)
Mulders P.1, Keane T.2, Fleshner N.3, Lawton C.4, Payne H.5, Taneja S.6 UMC St. Radboud, Dept. of Urology, Nijmegen, The Netherlands, 2Medical University of South Carolina, Urology, Charleston,, United States, 3Princess Margaret Hospital,, Urology, Toronto, Canada, 43medical College of Wisconsin, Medical Oncology, Milwaukee,, United States, 54meyerstein Institute of Oncology, Middlesex Hospital, Radiation Oncology, London, United Kingdom, 6New York University School of Medicine, Urology, New York, United States
1
INTRODUCTION & OBJECTIVES: Prostate cancer is slow growing. Therefore, usual 5-yr disease-free survival (DFS) rates cannot be used to ascertain cure. Current guidelines only classify radical prostatectomy (RP) and radiotherapy (RT) as being of curative intent. However, long-term data from studies of adjuvant hormonal therapy (AHT) in patients with poor-prognosis non-metastatic disease show that AHT also improves overall survival (OS), suggesting that patients who receive AHT may be cured. To test this, we analysed results of relevant trials against a more meaningful definition of prostate cancer cure. MATERIAL & METHODS: Kaplan-Meier DFS curves from other cancers were studied to form a model for cure applicable to prostate cancer. As a result, we propose a new definition of cure: “A treatment is curing patients when: a) the DFS curve associated with the treated population flattens and becomes parallel to, but separated from, the control normal population after 10-15 yrs; and b) non-cancer-related deaths in the treated population are not significantly different to those in the general population.” Data used were from long-term follow-up (>5 yrs) randomised trials of poor-prognosis non-metastatic prostate cancer (cN0, cM0, and either Gleason score >8; or PSA >20 ng/mL; or stage cT3/4; or adverse pathologic features) treated with an adjuvant LHRH agonist. RESULTS: Three trials met our requirements: RTOG 85-31 and EORTC 22863 (goserelin adjuvant to RT) and ECOG 7887 (goserelin or ochiectomy adjuvant to RP). Goserelin adjuvant to primary therapies was associated with significant OS benefit over standard care alone in each trial. At long-term follow-up (>5 yrs), the DFS curves for each population flattened towards infinity for the goserelin-treated men, indicating negligible future prostate cancer recurrence. Therefore, goserelin adjuvant to primary therapies meets our new cure definition. CONCLUSIONS: A substantial proportion of men with poor-prognosis non-metastatic prostate cancer are cured by goserelin adjuvant to primary therapies. Based on long-term data, we believe that adjuvant goserelin should be reclassified as a therapy of curative intent.
Collette L.1, Studer U.E.2, Whelan P.3, Albrecht W.4, Casselman J.5, De Reijke T.M.6, Hauri D.7, Loidl W.8, Isorna S.9, Sundaram S.K.10, Debois M.11 1 EORTC Data Centre, Biostatistics Unit, Brussels, Belgium, 2Inselspital, Urology Department, Berne, Switzerland, 3St James’ University Hospital, Urology Department, Leeds, United Kingdom, 4 Krankenanstalt Rudolfstiftung, Urology Department, Vienna, Austria, 5Damiaan Ziekenhuis, Urology Department, Oostende, Belgium, 6Academisch Medisch Centrum, Urology Department, Amsterdam, The Netherlands, 7University Hospital of Zürich, Urology Department, Zurich, Switzerland, 8 Krankenhaus Barmherzige Schwestern, Urology Department, Linz, Austria, 9Hospital N.d. del Pino, Urology Department, Las Palmas, Spain, 10Pinderfields Hospital, Urology Department, Wakefields, United Kingdom, 11EORTC, Data Centre, Brussels, Belgium
INTRODUCTION & OBJECTIVES: EORTC trial 30891 compared immediate endocrine treatment to deferred treatment initiated at the time of symptomatic disease progression or lifethreatening complications in 985 patients with T0-4N0M0 prostate cancer not suitable for local treatment with curative intent. We assessed baseline PSA, % decline from baseline PSA and decline below a threshold within the first months after initiation of treatment as prognostic factors for overall survival (OS), prostate cancer survival (PCS), objective progression-free survival (Obj PFS). We also assessed baseline PSA as predictor for time to PSA rise above 2 ng/ml in 272 cases who reached a PSA nadir<2 ng/ml. MATERIAL & METHODS: Data from 340 eligible patients treated immediately with orchiectomy or LH-RH analog, who had a baseline PSA >=4 ng/ml and were followed for minimum 1 year by PSA tests were used. Baseline PSA level (with cut points at 8, 20 and 50 ng/ml), %decline from baseline (with cut points at 50%, 90%, 95% and 98%) and lowering below a threshold of (0.2 ng/ml, 0.5 ng/ml, 1 ng/ml or 2 ng/ml) were studied for prognostic effect by Logrank test (alpha=0.05). A landmark of 9 months was used for the latter two factors. RESULTS: Patients were in 73 years old in median (54-80); had a baseline PSA of 10.1 ng/mL (4.0-720); presented with T2-4 disease in 82.9%; G1: 27.1%, G2: 54.4%, G3: 17.6%. After a median follow-up of 8 years, baseline PSA level was not prognostic for OS (P>0.1), nor for PCS (P=0.061), nor for objective PFS (P>0.1). Despite that 19.8% of the patients had a PSA decline by 90%, 32.8% by 95% and 26.7% by >=8% during the landmark; the % PSA decline was not predictive for any of the three endpoints (P>0.1 for each). During the landmark, 21.5%,19.3%, 20.9% and 20.2% of the patients had their PSA declining below 0.2 ng/ml, 0.5 ng/ml, 1 ng/ml and 2 ng/ml, respectively and 18.1% maintained a PSA>2 ng/ml. This was also not predictive of long term outcome (P>0.1 for OS and PCS, P=0.10 for objective PFS). In 272 patients who eventually reached a nadir <2 ng/ml, the median time to the PSA rising above 2 ng/ml was 6.4 years. The risk of PSA rise after decline <2 ng/ ml was greater for higher baseline PSA (P<0.0001) by univariate analysis, as well as after adjustment for other predictors. CONCLUSIONS: Baseline PSA and PSA decline on treatment are not useful predictors of long term outcome in androgen deprived patients with T0-4N0M0 prostate cancer but initial PSA predicts for time to PSA relapse after PSA nadir <2 ng/ml.
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RISE OF SERUM PSA AND TESTOSTERONE FOLLOWING ANDROGEN ABLATION: PRELIMINARY DATA IN PATIENTS WITH INTERMITTENT ANDROGEN DEPRIVATION THERAPY FOR METASTATIC PROSTATE CANCER
INTERMITTENT HORMONE THERAPY FOR ADVANCED AND NONLOCALISED PROSTATE CANCER
Han D.H., Choo S.H., Jung B.J., Jeon S.S., Lee H.M., Choi H.Y.
Institut Mutualiste Montsouris, Université René Descartes Paris V, Uology, Paris, France
Samsung Medical Centre, Sungkyunkwan University School of Medicine, Urology, Seoul, South Korea INTRODUCTION & OBJECTIVES: It seems to be important that normal level of testosterone (T) could be attained during off-treatment period of intermittent androgen deprivation (IAD) for the quality of life of patients. There are a few clinical trials that specially studied the kinetics of the increase of T following androgen ablation for prostate cancer (PCa). However there is few data about the relationships between the increase of serum prostate specific antigen (PSA) and T. We investigated the timing of T increase after cessation of hormonal therapy, and the increase of PSA related to the rise of T during the first off-treatment period of IAD. MATERIAL & METHODS: A total of 37 patients (mean age, 71.1 years) who underwent more than 1 cycle of IAD for metastatic PCa were surveyed. PSA and T measurement were taken monthly during IAD. Therapy was started when the PSA level rose to ≥20 ng/ml or more than 50% of initial level. Therapy was discontinued in case PSA fell to below 4ng/ml. All patients completed 81 cycles (2.2 cycles/patient, range 1-5). After a mean follow-up of 44.89 months (range 21-123), 16 patients presented progression and 1 patient died after 96 months. RESULTS: In first cycle of IAD, mean on-treatment and off-treatment duration was 10.41 months (range 6-25) and 8.28 months (range 3-39). 43.2% (±11.33%) of time was spent for off-treatment. Mean PSA before treatment was 664.5ng/ml (range 10.2-6690) and T was 3.97 (±1.72) ng/ml. Mean nadir PSA during on-treatment was 0.58 (±0.73) ng/ml and 18 patients showed reduction of T to undetectable level (<0.2 ng/ml). Mean time to reach nadir PSA was 6.57 (±3.39) months. After mean 1.41 months (range 1-6), T level decreased to castration level (<0.5 ng/ml). Thirty-six patients (97.3%) could have a mean time of 1.67 months (range 1-6) to T≥ 0.5 ng/ml after discontinuation of hormonal therapy. However in 1, T did not reach 0.5 ng/ml before beginning of 2nd cycle. Twenty-eight (75.7%) showed increased T to normal range (≥2.79 ng/ml) after a mean time of 3.86 (range 1-12) months, but T did not reach normal range before beginning of 2nd cycle in 9 (24.3%). In 33 patients (89.2%), the increase of T to non-castration level preceded PSA escape (defined as PSA level ≥4.0 ng/ml). And the mean duration from the time T ≥0.5ng/ml till PSA escape was 3.06 months (range 0-28). However, 4 showed PSA escape in spite of castration level of T. Eighteen patients (48.6%) showed PSA escape after increase of T to normal range and the mean duration was 2.83 months (range 0-25). However in 19 (51.4%), PSA escape was developed even before T reached normal range. CONCLUSIONS: T returned to non-castration and normal level just 1.67 and 3.86 months after discontinuation of hormonal therapy respectively. PSA increased to higher than 4.0 ng/ml 3 months after testosterone rise to non-castration level. More than half of patients showed PSA escape before T reached normal range and 24% of patients showed T level below normal range during overall offtreatment period.
Eur Urol Suppl 2006;5(2):288
Prapotnich D., Cathala N., Mombet A., Cathelineau X., Rozet F., Barret E., Vallancien G.
INTRODUCTION & OBJECTIVES: Biochemical failure after radical treatment for prostate cancer or non-localised disease is frequently treated by androgen deprivation. Intermittent hormone therapy (IHT) may offer possible treatment modalities for these metastatic patients in order to reduce morbidity of hormonal withdrawal. MATERIAL & METHODS: 467 patients have been included in an IHT protocol since 1992. 103 patients after having a biological recurrence following a radical prostatectomy, 70 patients had previous radiotherapy or treatment with high-intensity focused ultrasound (HIFU) and 294 patients had not received any previous treatment. Threemonthly injection of LHRH analogue combined with a non-steroidal anti-androgen was administered during the treatment phase (phase on). Treatment was stopped (phase off) when the PSA level fell below 4 ng/ml regardless the duration of the treatment phase. Criteria for resumption of hormonal therapy were either PSA > 20 ng/ml, PSA progression slope over the previous 3 months > 5 ng/ml per month or the recurrence of any urinary symptoms or pain. RESULTS: The median follow-up was 60.5 months (5-156) after the onset of IHT. The median PSA prior to IHT was 19.7 ng/ml (2-433). Median age at the beginning of IHT was 73.7 years (52-92). 9 cycles were performed in patients with the longest follow-up. The length of the treatment cycles gradually decreased from a median of 22 months to 13 months through the fifth cycle and then stabilized at a median of 12 months till the 9th cycle. The ratio (phase on/phase off) between the duration of the treatment phase and the duration of the surveillance phase was close to 40% (34-43) regardless of the nine cycles. 50 patients died during the study, 24 (5%) from their prostate cancer. 14 patients (3%) developed painful symptoms or urinary disturbances during IHT (most of them had a high PSA level >100 ng/ml at the entry or were painful). CONCLUSIONS: IHT is a feasible and safe treatment option for locally advanced or metastatic patient with prostate cancer ensuring a long term (5 years) control of the disease without major complications. Poor candidates for IHT were patients with initial high PSA (>100 ng/ml) or bulky tumours with many involved lymph nodes or painful bone metastases.
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MEN WITH POOR-PROGNOSIS NON-METASTATIC PROSTATE CANCER CAN BE CURED WITH ADJUVANT ANDROGEN DEPRIVATION THERAPY
IS THE DEGREE OF PSA DECLINE AFTER IMMEDIATE ANDROGEN DEPRIVATION A PROGNOSTIC FACTOR FOR OUTCOME IN PATIENTS WITH T0-4 N0 M0 PROSTATE CANCER NOT SUITABLE FOR LOCAL TREATMENT WITH CURATIVE INTENT? (RESULTS FROM THE EORTC 30891 TRIAL)
Mulders P.1, Keane T.2, Fleshner N.3, Lawton C.4, Payne H.5, Taneja S.6 UMC St. Radboud, Dept. of Urology, Nijmegen, The Netherlands, 2Medical University of South Carolina, Urology, Charleston,, United States, 3Princess Margaret Hospital,, Urology, Toronto, Canada, 43medical College of Wisconsin, Medical Oncology, Milwaukee,, United States, 54meyerstein Institute of Oncology, Middlesex Hospital, Radiation Oncology, London, United Kingdom, 6New York University School of Medicine, Urology, New York, United States
1
INTRODUCTION & OBJECTIVES: Prostate cancer is slow growing. Therefore, usual 5-yr disease-free survival (DFS) rates cannot be used to ascertain cure. Current guidelines only classify radical prostatectomy (RP) and radiotherapy (RT) as being of curative intent. However, long-term data from studies of adjuvant hormonal therapy (AHT) in patients with poor-prognosis non-metastatic disease show that AHT also improves overall survival (OS), suggesting that patients who receive AHT may be cured. To test this, we analysed results of relevant trials against a more meaningful definition of prostate cancer cure. MATERIAL & METHODS: Kaplan-Meier DFS curves from other cancers were studied to form a model for cure applicable to prostate cancer. As a result, we propose a new definition of cure: “A treatment is curing patients when: a) the DFS curve associated with the treated population flattens and becomes parallel to, but separated from, the control normal population after 10-15 yrs; and b) non-cancer-related deaths in the treated population are not significantly different to those in the general population.” Data used were from long-term follow-up (>5 yrs) randomised trials of poor-prognosis non-metastatic prostate cancer (cN0, cM0, and either Gleason score >8; or PSA >20 ng/mL; or stage cT3/4; or adverse pathologic features) treated with an adjuvant LHRH agonist. RESULTS: Three trials met our requirements: RTOG 85-31 and EORTC 22863 (goserelin adjuvant to RT) and ECOG 7887 (goserelin or ochiectomy adjuvant to RP). Goserelin adjuvant to primary therapies was associated with significant OS benefit over standard care alone in each trial. At long-term follow-up (>5 yrs), the DFS curves for each population flattened towards infinity for the goserelin-treated men, indicating negligible future prostate cancer recurrence. Therefore, goserelin adjuvant to primary therapies meets our new cure definition. CONCLUSIONS: A substantial proportion of men with poor-prognosis non-metastatic prostate cancer are cured by goserelin adjuvant to primary therapies. Based on long-term data, we believe that adjuvant goserelin should be reclassified as a therapy of curative intent.
Collette L.1, Studer U.E.2, Whelan P.3, Albrecht W.4, Casselman J.5, De Reijke T.M.6, Hauri D.7, Loidl W.8, Isorna S.9, Sundaram S.K.10, Debois M.11 1 EORTC Data Centre, Biostatistics Unit, Brussels, Belgium, 2Inselspital, Urology Department, Berne, Switzerland, 3St James’ University Hospital, Urology Department, Leeds, United Kingdom, 4 Krankenanstalt Rudolfstiftung, Urology Department, Vienna, Austria, 5Damiaan Ziekenhuis, Urology Department, Oostende, Belgium, 6Academisch Medisch Centrum, Urology Department, Amsterdam, The Netherlands, 7University Hospital of Zürich, Urology Department, Zurich, Switzerland, 8 Krankenhaus Barmherzige Schwestern, Urology Department, Linz, Austria, 9Hospital N.d. del Pino, Urology Department, Las Palmas, Spain, 10Pinderfields Hospital, Urology Department, Wakefields, United Kingdom, 11EORTC, Data Centre, Brussels, Belgium
INTRODUCTION & OBJECTIVES: EORTC trial 30891 compared immediate endocrine treatment to deferred treatment initiated at the time of symptomatic disease progression or lifethreatening complications in 985 patients with T0-4N0M0 prostate cancer not suitable for local treatment with curative intent. We assessed baseline PSA, % decline from baseline PSA and decline below a threshold within the first months after initiation of treatment as prognostic factors for overall survival (OS), prostate cancer survival (PCS), objective progression-free survival (Obj PFS). We also assessed baseline PSA as predictor for time to PSA rise above 2 ng/ml in 272 cases who reached a PSA nadir<2 ng/ml. MATERIAL & METHODS: Data from 340 eligible patients treated immediately with orchiectomy or LH-RH analog, who had a baseline PSA >=4 ng/ml and were followed for minimum 1 year by PSA tests were used. Baseline PSA level (with cut points at 8, 20 and 50 ng/ml), %decline from baseline (with cut points at 50%, 90%, 95% and 98%) and lowering below a threshold of (0.2 ng/ml, 0.5 ng/ml, 1 ng/ml or 2 ng/ml) were studied for prognostic effect by Logrank test (alpha=0.05). A landmark of 9 months was used for the latter two factors. RESULTS: Patients were in 73 years old in median (54-80); had a baseline PSA of 10.1 ng/mL (4.0-720); presented with T2-4 disease in 82.9%; G1: 27.1%, G2: 54.4%, G3: 17.6%. After a median follow-up of 8 years, baseline PSA level was not prognostic for OS (P>0.1), nor for PCS (P=0.061), nor for objective PFS (P>0.1). Despite that 19.8% of the patients had a PSA decline by 90%, 32.8% by 95% and 26.7% by >=8% during the landmark; the % PSA decline was not predictive for any of the three endpoints (P>0.1 for each). During the landmark, 21.5%,19.3%, 20.9% and 20.2% of the patients had their PSA declining below 0.2 ng/ml, 0.5 ng/ml, 1 ng/ml and 2 ng/ml, respectively and 18.1% maintained a PSA>2 ng/ml. This was also not predictive of long term outcome (P>0.1 for OS and PCS, P=0.10 for objective PFS). In 272 patients who eventually reached a nadir <2 ng/ml, the median time to the PSA rising above 2 ng/ml was 6.4 years. The risk of PSA rise after decline <2 ng/ ml was greater for higher baseline PSA (P<0.0001) by univariate analysis, as well as after adjustment for other predictors. CONCLUSIONS: Baseline PSA and PSA decline on treatment are not useful predictors of long term outcome in androgen deprived patients with T0-4N0M0 prostate cancer but initial PSA predicts for time to PSA relapse after PSA nadir <2 ng/ml.
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RISE OF SERUM PSA AND TESTOSTERONE FOLLOWING ANDROGEN ABLATION: PRELIMINARY DATA IN PATIENTS WITH INTERMITTENT ANDROGEN DEPRIVATION THERAPY FOR METASTATIC PROSTATE CANCER
INTERMITTENT HORMONE THERAPY FOR ADVANCED AND NONLOCALISED PROSTATE CANCER
Han D.H., Choo S.H., Jung B.J., Jeon S.S., Lee H.M., Choi H.Y.
Institut Mutualiste Montsouris, Université René Descartes Paris V, Uology, Paris, France
Samsung Medical Centre, Sungkyunkwan University School of Medicine, Urology, Seoul, South Korea INTRODUCTION & OBJECTIVES: It seems to be important that normal level of testosterone (T) could be attained during off-treatment period of intermittent androgen deprivation (IAD) for the quality of life of patients. There are a few clinical trials that specially studied the kinetics of the increase of T following androgen ablation for prostate cancer (PCa). However there is few data about the relationships between the increase of serum prostate specific antigen (PSA) and T. We investigated the timing of T increase after cessation of hormonal therapy, and the increase of PSA related to the rise of T during the first off-treatment period of IAD. MATERIAL & METHODS: A total of 37 patients (mean age, 71.1 years) who underwent more than 1 cycle of IAD for metastatic PCa were surveyed. PSA and T measurement were taken monthly during IAD. Therapy was started when the PSA level rose to ≥20 ng/ml or more than 50% of initial level. Therapy was discontinued in case PSA fell to below 4ng/ml. All patients completed 81 cycles (2.2 cycles/patient, range 1-5). After a mean follow-up of 44.89 months (range 21-123), 16 patients presented progression and 1 patient died after 96 months. RESULTS: In first cycle of IAD, mean on-treatment and off-treatment duration was 10.41 months (range 6-25) and 8.28 months (range 3-39). 43.2% (±11.33%) of time was spent for off-treatment. Mean PSA before treatment was 664.5ng/ml (range 10.2-6690) and T was 3.97 (±1.72) ng/ml. Mean nadir PSA during on-treatment was 0.58 (±0.73) ng/ml and 18 patients showed reduction of T to undetectable level (<0.2 ng/ml). Mean time to reach nadir PSA was 6.57 (±3.39) months. After mean 1.41 months (range 1-6), T level decreased to castration level (<0.5 ng/ml). Thirty-six patients (97.3%) could have a mean time of 1.67 months (range 1-6) to T≥ 0.5 ng/ml after discontinuation of hormonal therapy. However in 1, T did not reach 0.5 ng/ml before beginning of 2nd cycle. Twenty-eight (75.7%) showed increased T to normal range (≥2.79 ng/ml) after a mean time of 3.86 (range 1-12) months, but T did not reach normal range before beginning of 2nd cycle in 9 (24.3%). In 33 patients (89.2%), the increase of T to non-castration level preceded PSA escape (defined as PSA level ≥4.0 ng/ml). And the mean duration from the time T ≥0.5ng/ml till PSA escape was 3.06 months (range 0-28). However, 4 showed PSA escape in spite of castration level of T. Eighteen patients (48.6%) showed PSA escape after increase of T to normal range and the mean duration was 2.83 months (range 0-25). However in 19 (51.4%), PSA escape was developed even before T reached normal range. CONCLUSIONS: T returned to non-castration and normal level just 1.67 and 3.86 months after discontinuation of hormonal therapy respectively. PSA increased to higher than 4.0 ng/ml 3 months after testosterone rise to non-castration level. More than half of patients showed PSA escape before T reached normal range and 24% of patients showed T level below normal range during overall offtreatment period.
Eur Urol Suppl 2006;5(2):288
Prapotnich D., Cathala N., Mombet A., Cathelineau X., Rozet F., Barret E., Vallancien G.
INTRODUCTION & OBJECTIVES: Biochemical failure after radical treatment for prostate cancer or non-localised disease is frequently treated by androgen deprivation. Intermittent hormone therapy (IHT) may offer possible treatment modalities for these metastatic patients in order to reduce morbidity of hormonal withdrawal. MATERIAL & METHODS: 467 patients have been included in an IHT protocol since 1992. 103 patients after having a biological recurrence following a radical prostatectomy, 70 patients had previous radiotherapy or treatment with high-intensity focused ultrasound (HIFU) and 294 patients had not received any previous treatment. Threemonthly injection of LHRH analogue combined with a non-steroidal anti-androgen was administered during the treatment phase (phase on). Treatment was stopped (phase off) when the PSA level fell below 4 ng/ml regardless the duration of the treatment phase. Criteria for resumption of hormonal therapy were either PSA > 20 ng/ml, PSA progression slope over the previous 3 months > 5 ng/ml per month or the recurrence of any urinary symptoms or pain. RESULTS: The median follow-up was 60.5 months (5-156) after the onset of IHT. The median PSA prior to IHT was 19.7 ng/ml (2-433). Median age at the beginning of IHT was 73.7 years (52-92). 9 cycles were performed in patients with the longest follow-up. The length of the treatment cycles gradually decreased from a median of 22 months to 13 months through the fifth cycle and then stabilized at a median of 12 months till the 9th cycle. The ratio (phase on/phase off) between the duration of the treatment phase and the duration of the surveillance phase was close to 40% (34-43) regardless of the nine cycles. 50 patients died during the study, 24 (5%) from their prostate cancer. 14 patients (3%) developed painful symptoms or urinary disturbances during IHT (most of them had a high PSA level >100 ng/ml at the entry or were painful). CONCLUSIONS: IHT is a feasible and safe treatment option for locally advanced or metastatic patient with prostate cancer ensuring a long term (5 years) control of the disease without major complications. Poor candidates for IHT were patients with initial high PSA (>100 ng/ml) or bulky tumours with many involved lymph nodes or painful bone metastases.