5007 Background: This randomized, prospective phase III trial investigated if immediate intervent... more 5007 Background: This randomized, prospective phase III trial investigated if immediate intervention with androgen deprivation therapy (ADT) (Arm B) improved overall survival compared to delayed AD...
Purpose. Survival following biochemical failure is highly variable. Using a randomized trial data... more Purpose. Survival following biochemical failure is highly variable. Using a randomized trial dataset, we sought to define a risk stratification scheme in men with locally advanced prostate cancer (LAPC).Methods. The TROG 96.01 trial randomized 802 men with LAPC to radiation ± neoadjuvant androgen suppression therapy (AST) between 1996 and 2000. Ten-year follow-up data was used to develop three-tier post-biochemical failure risk stratification schemes based on cutpoints of time to biochemical failure (TTBF) and PSA doubling time (PSADT). Schemes were evaluated in univariable, competing risk models for prostate cancer-specific mortality. The performance was assessed by c-indices and internally validated by the simple bootstrap method. Performance rankings were compared in sensitivity analyses using multivariable models and variations in PSADT calculation.Results. 485 men developed biochemical failure. c-indices ranged between 0.630 and 0.730. The most discriminatory scheme had a high ...
We investigated whether 18 months of androgen suppression plus radiotherapy, with or without 18 m... more We investigated whether 18 months of androgen suppression plus radiotherapy, with or without 18 months of zoledronic acid, is more effective than 6 months of neoadjuvant androgen suppression plus radiotherapy with or without zoledronic acid. We did an open-label, randomised, 2 × 2 factorial trial in men with locally advanced prostate cancer (either T2a N0 M0 prostatic adenocarcinomas with prostate-specific antigen [PSA] ≥10 μg/L and a Gleason score of ≥7, or T2b-4 N0 M0 tumours regardless of PSA and Gleason score). We randomly allocated patients by computer-generated minimisation--stratified by centre, baseline PSA, tumour stage, Gleason score, and use of a brachytherapy boost--to one of four groups in a 1:1:1:1 ratio. Patients in the control group were treated with neoadjuvant androgen suppression with leuprorelin (22·5 mg every 3 months, intramuscularly) for 6 months (short-term) and radiotherapy alone (designated STAS); this procedure was either followed by another 12 months of a...
Journal of Medical Imaging and Radiation Oncology, 2010
External beam radiotherapy for prostate cancer has undergone substantial technological and clinic... more External beam radiotherapy for prostate cancer has undergone substantial technological and clinical advances in the recent years. The Australian & New Zealand Faculty of Radiation Oncology Genito-Urinary Group undertook a process to develop consensus clinical practice guidelines for external beam radiotherapy for prostate carcinoma delivered with curative intent, aiming to provide guidance for clinicians on the appropriate integration of clinical evidence and newer technologies. Draft guidelines were presented and discussed at a consensus workshop in May 2009 attended by radiation oncologists, radiation therapists and medical physicists. Amended guidelines were distributed to radiation oncologists in Australia, New Zealand and Singapore for comment, and modifications were incorporated where appropriate. Evidence based recommendations for risk stratification, the role of image-guided and intensity-modulated radiation therapy, prescribed dose, simulation and treatment planning, the role and duration of neo-adjuvant/adjuvant androgen deprivation therapy and outcome reporting are presented. Central to the guidelines is the recommendation that image-guided radiation therapy should be used when definitive external beam radiotherapy for prostate cancer is prescribed. The consensus guidelines provide a co-operatively developed, evidence-based framework for contemporary treatment of prostate cancer with external beam radiotherapy.
The objective of the present study was to examine prostate-specific antigen relapse free survival... more The objective of the present study was to examine prostate-specific antigen relapse free survival (PSA-RFS) and morbidity following 'conventional' radical radiation therapy for prostate cancer in two Australian regional treatment services. Four hundred and eighty men with clinically localized prostate cancer were treated between 1993 and 1997 at Liverpool and Westmead Hospitals using a standardized 4-field, CT-planned radiotherapy technique. Principal endpoints were PSA-RFS (American Society for Therapeutic Radiology and Oncology guidelines definition) and late rectal and urinary morbidity (Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria). The median follow up of patients from the end of RT was 55 months. Prospectively, they were divided into three prognostic categories: (i) high risk T3 or 4 and/or PSA > 20 ng/mL and/or Gleason score 8-10 (40% of cohort); (ii) intermediate risk T1 or 2 and PSA 10-20 ng/mL and/or Gleason score 7 (33% of cohort); and (iii) low risk T1 or 2 and PSA < 10 ng/mL and Gleason score < 6 (27% of cohort). The 5-year actuarial PSA-RFS was 53% for the whole patient group. The 4-year rates were 32, 56 and 75% for high, intermediate and low risk groups, respectively. On multivariate analysis, T-stage, Gleason score, pre-RT-PSA were strong independent predictors of PSA-defined outcome. Late (grade 2) rectal and urinary morbidity occurred at some point in time in the post-RT period in 8.0 and 5.8% of patients, respectively. These results confirm that low Gleason score, low T stage, presenting PSA < 10 ng/mL and nadir < 1 ng/mL remain the strongest predictors of a good outcome. Long-term toxicity was very acceptable. However, further improvement in outcome is desirable, and with the adoption of new technology allowing escalation of radiotherapy doses such an expectation might be achieved.
Androgen deprivation is an established treatment regimen for disseminated prostate cancer; howeve... more Androgen deprivation is an established treatment regimen for disseminated prostate cancer; however, its role in patients with localised cancer is less clear. We did a large randomised controlled trial to determine whether 3 months or 6 months of androgen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer. 818 men with locally advanced prostate cancer were randomly assigned to: no androgen deprivation (ie, radiotherapy alone: 66 Gy in 33 fractions of 2 Gy per day over 6.5-7.0 weeks to the prostate and seminal vesicles); 3 months' androgen deprivation with 3.6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy (same regimen as control group); or 6 months' androgen deprivation, with the same regimen, starting 5 months before radiotherapy (same regimen as control group). Primary endpoints were time to local failure and prostate-cancer-specific survival; secondary endpoints were distant failure, disease-free survival, and freedom from salvage treatment. Analyses were done by intention to treat. 802 (98%) patients were eligible for analysis. Median follow-up was 5.9 years (range 0.1-8.5). Compared with patients assigned no androgen deprivation, those assigned 3…
5007 Background: This randomized, prospective phase III trial investigated if immediate intervent... more 5007 Background: This randomized, prospective phase III trial investigated if immediate intervention with androgen deprivation therapy (ADT) (Arm B) improved overall survival compared to delayed AD...
Purpose. Survival following biochemical failure is highly variable. Using a randomized trial data... more Purpose. Survival following biochemical failure is highly variable. Using a randomized trial dataset, we sought to define a risk stratification scheme in men with locally advanced prostate cancer (LAPC).Methods. The TROG 96.01 trial randomized 802 men with LAPC to radiation ± neoadjuvant androgen suppression therapy (AST) between 1996 and 2000. Ten-year follow-up data was used to develop three-tier post-biochemical failure risk stratification schemes based on cutpoints of time to biochemical failure (TTBF) and PSA doubling time (PSADT). Schemes were evaluated in univariable, competing risk models for prostate cancer-specific mortality. The performance was assessed by c-indices and internally validated by the simple bootstrap method. Performance rankings were compared in sensitivity analyses using multivariable models and variations in PSADT calculation.Results. 485 men developed biochemical failure. c-indices ranged between 0.630 and 0.730. The most discriminatory scheme had a high ...
We investigated whether 18 months of androgen suppression plus radiotherapy, with or without 18 m... more We investigated whether 18 months of androgen suppression plus radiotherapy, with or without 18 months of zoledronic acid, is more effective than 6 months of neoadjuvant androgen suppression plus radiotherapy with or without zoledronic acid. We did an open-label, randomised, 2 × 2 factorial trial in men with locally advanced prostate cancer (either T2a N0 M0 prostatic adenocarcinomas with prostate-specific antigen [PSA] ≥10 μg/L and a Gleason score of ≥7, or T2b-4 N0 M0 tumours regardless of PSA and Gleason score). We randomly allocated patients by computer-generated minimisation--stratified by centre, baseline PSA, tumour stage, Gleason score, and use of a brachytherapy boost--to one of four groups in a 1:1:1:1 ratio. Patients in the control group were treated with neoadjuvant androgen suppression with leuprorelin (22·5 mg every 3 months, intramuscularly) for 6 months (short-term) and radiotherapy alone (designated STAS); this procedure was either followed by another 12 months of a...
Journal of Medical Imaging and Radiation Oncology, 2010
External beam radiotherapy for prostate cancer has undergone substantial technological and clinic... more External beam radiotherapy for prostate cancer has undergone substantial technological and clinical advances in the recent years. The Australian & New Zealand Faculty of Radiation Oncology Genito-Urinary Group undertook a process to develop consensus clinical practice guidelines for external beam radiotherapy for prostate carcinoma delivered with curative intent, aiming to provide guidance for clinicians on the appropriate integration of clinical evidence and newer technologies. Draft guidelines were presented and discussed at a consensus workshop in May 2009 attended by radiation oncologists, radiation therapists and medical physicists. Amended guidelines were distributed to radiation oncologists in Australia, New Zealand and Singapore for comment, and modifications were incorporated where appropriate. Evidence based recommendations for risk stratification, the role of image-guided and intensity-modulated radiation therapy, prescribed dose, simulation and treatment planning, the role and duration of neo-adjuvant/adjuvant androgen deprivation therapy and outcome reporting are presented. Central to the guidelines is the recommendation that image-guided radiation therapy should be used when definitive external beam radiotherapy for prostate cancer is prescribed. The consensus guidelines provide a co-operatively developed, evidence-based framework for contemporary treatment of prostate cancer with external beam radiotherapy.
The objective of the present study was to examine prostate-specific antigen relapse free survival... more The objective of the present study was to examine prostate-specific antigen relapse free survival (PSA-RFS) and morbidity following 'conventional' radical radiation therapy for prostate cancer in two Australian regional treatment services. Four hundred and eighty men with clinically localized prostate cancer were treated between 1993 and 1997 at Liverpool and Westmead Hospitals using a standardized 4-field, CT-planned radiotherapy technique. Principal endpoints were PSA-RFS (American Society for Therapeutic Radiology and Oncology guidelines definition) and late rectal and urinary morbidity (Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria). The median follow up of patients from the end of RT was 55 months. Prospectively, they were divided into three prognostic categories: (i) high risk T3 or 4 and/or PSA > 20 ng/mL and/or Gleason score 8-10 (40% of cohort); (ii) intermediate risk T1 or 2 and PSA 10-20 ng/mL and/or Gleason score 7 (33% of cohort); and (iii) low risk T1 or 2 and PSA < 10 ng/mL and Gleason score < 6 (27% of cohort). The 5-year actuarial PSA-RFS was 53% for the whole patient group. The 4-year rates were 32, 56 and 75% for high, intermediate and low risk groups, respectively. On multivariate analysis, T-stage, Gleason score, pre-RT-PSA were strong independent predictors of PSA-defined outcome. Late (grade 2) rectal and urinary morbidity occurred at some point in time in the post-RT period in 8.0 and 5.8% of patients, respectively. These results confirm that low Gleason score, low T stage, presenting PSA < 10 ng/mL and nadir < 1 ng/mL remain the strongest predictors of a good outcome. Long-term toxicity was very acceptable. However, further improvement in outcome is desirable, and with the adoption of new technology allowing escalation of radiotherapy doses such an expectation might be achieved.
Androgen deprivation is an established treatment regimen for disseminated prostate cancer; howeve... more Androgen deprivation is an established treatment regimen for disseminated prostate cancer; however, its role in patients with localised cancer is less clear. We did a large randomised controlled trial to determine whether 3 months or 6 months of androgen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer. 818 men with locally advanced prostate cancer were randomly assigned to: no androgen deprivation (ie, radiotherapy alone: 66 Gy in 33 fractions of 2 Gy per day over 6.5-7.0 weeks to the prostate and seminal vesicles); 3 months' androgen deprivation with 3.6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy (same regimen as control group); or 6 months' androgen deprivation, with the same regimen, starting 5 months before radiotherapy (same regimen as control group). Primary endpoints were time to local failure and prostate-cancer-specific survival; secondary endpoints were distant failure, disease-free survival, and freedom from salvage treatment. Analyses were done by intention to treat. 802 (98%) patients were eligible for analysis. Median follow-up was 5.9 years (range 0.1-8.5). Compared with patients assigned no androgen deprivation, those assigned 3…
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