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From 2004–2009 a total of 226 out of a target of 750 prostate cancer patients have been randomised into the Timing of Androgen Deprivation trial between immediate and delayed androgen deprivation. A screening log was kept by participating centres for the first 928 patients, which documented the reasons for non-entry into the trial; 42.7% of screened patients were ineligible and a further 33.0% were not entered for other reasons. Fewer than 10% of patients cited not wanting to be part of a clinical trial as a reason for non-entry. Strategies to improve recruitment included broadening the eligibility criteria, encouraging international collaboration, the use and support of research nurses in the private health care environment, and the use of phone follow-up. Recruitment will be completed at the number originally intended to inform the interim analysis designed to test the validity of the statistical assumptions, and a combined survival analysis with the Canadian study is planned. [ABSTRACT FROM AUTHOR]

Objective: To assess psychosocial distress in patients with early (localised) and advanced (metastatic) prostate cancer (PCA) at diagnosis (Time 1) and 12 months later (Time 2), and identify psychosocial factors predictive of later distress.Design, Participants and Setting: Observational, prospective study of 367 men with early (211) or advanced (156) PCA recruited as consecutive attendees at clinics at seven public hospitals and practices in metropolitan Melbourne between 1 April 2001 and 30 December 2005. Both groups completed questionnaires at Time 1 and Time 2.Main Outcome Measures: Health-related quality of life as assessed by the Short Form 36-item Health Survey; psychological distress, including depression and anxiety as assessed by the Brief Symptom Inventory; and coping patterns as assessed by the Mini-Mental Adjustment to Cancer scale.Results: Over the 12 months, both the early and advanced PCA group showed reduced vitality and increased depression and anxiety; this effect was greater in the advanced PCA group. Mental health, social functioning and role-emotional functioning also deteriorated in the advanced group. Predictors of depression at Time 2 for the early PCA group were depression, vitality and a fatalistic coping pattern at Time 1; anxiety at Time 2 was predicted by anxiety and vitality at Time 1. In the advanced PCA group, depression at Time 2 was predicted by depression and mental health at Time 1; anxiety at Time 2 was predicted by anxiety, mental health, cognitive avoidance and lower anxious preoccupation at Time 1.Conclusions: Men with early PCA experience decreasing vitality and increasing psychological distress over the 12 months following diagnosis; this trend is accelerated after diagnosis with advanced PCA. A fatalistic coping pattern at diagnosis of early PCA predicts later depression while cognitive avoidance and lower anxious preoccupation at diagnosis of advanced PCA predict later anxiety. [ABSTRACT FROM AUTHOR]

Objective: To assess the psychological impact of the different treatments for localised prostate cancer (PCA).Design, Participants and Setting: Observational, prospective study of consecutive patients with PCA attending clinics in public hospitals and private practices in metropolitan Melbourne between 1 April 2001 and 30 December 2005. Data were collected at initial diagnosis of histologically confirmed localised PCA, and close to the commencement of definitive treatment (Time 1), and 12 months later (Time 2). Patients were stratified according to treatment type (radical prostatectomy [RP], hormone therapy [HT] or other early treatment including radiation therapies [OET]). Patients who elected to undergo active surveillance/watchful waiting (WW) rather than active treatment were treated as a naturalistic control group.Main Outcome Measures: Levels of depression and anxiety were assessed by the Brief Symptom Inventory, and physical and psychosocial aspects of health-related quality of life (HRQOL) were assessed by the 36-item Short-Form Health Survey.Results: 211 patients with PCA were recruited; 193 completed the Time 1 questionnaires (38 RP, 56 HT, 38 OET and 61 WW); and 172 completed the Time 2 questionnaires (33 RP, 51 HT, 33 OET and 55 WW). At Time 1, the three active treatment groups all reported greater dysfunction in work role and daily activities compared with the WW group. The RP group also reported worse social and emotional role functioning, while the HT and OET groups reported poorer vitality levels. The HT group reported significantly higher depression scores. At Time 2, the RP and OET groups did not differ from the WW group on either HRQOL or psychological status. By contrast, the HT group reported significantly worse HRQOL (physical functioning, role-physical and vitality domains) and greater psychological distress compared with the WW group.Conclusions: Compared with the other active treatments for localised PCA, HT appears to be associated with poorer HRQOL and greater psychological distress 12 months after commencing treatment. [ABSTRACT FROM AUTHOR]

Background: The Timing Of Androgen Deprivation (TOAD) trial found an overall survival benefit for immediate vs delayed androgen deprivation therapy (ADT) for prostate-specific antigen (PSA)-relapsed or noncurable prostate cancer. However, broad eligibility criteria allowed entry of a heterogeneous participant group, including those with prior ADT exposure, raising concerns about subsequent androgen sensitivity. For these reasons, we completed previously specified subgroup analyses to assess if prior ADT was associated with ADT timing efficacy after PSA relapse., Methods: We examined TOAD trial patient-level data for participants with PSA relapse after local therapy. We performed Kaplan-Meier analyses for overall survival stratified by prior ADT and randomized treatment arm (immediate or delayed ADT). We compared group characteristics using Mann-Whitney U and Fisher exact tests. All hypothesis tests were 2-sided., Results: We identified 261 patients with PSA relapse, 125 of whom received prior ADT. Patients with prior ADT had higher PSA at presentation (12.1 vs 9.0 ng/mL; P < .001), more cT3 disease (38.4% vs 25.0%; P = .007), and more likely received radiotherapy as local treatment (80.0% vs 47.8%; P < .001) but were otherwise similar to patients without prior ADT exposure. Within this prior ADT group, those who received immediate ADT (n = 56) had improved overall survival compared with those who received delayed ADT (n = 69; P = .02). This benefit was not observed in the group with no prior ADT (P = .98)., Conclusions: The survival benefit demonstrated in the TOAD trial may be driven by patients who received ADT prior to trial entry. We provide possible explanations for this finding with implications for treatment of PSA-relapsed prostate cancer and future study planning., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Adjuvant radiotherapy has been shown to halve the risk of biochemical progression for patients with high-risk disease after radical prostatectomy. Early salvage radiotherapy could result in similar biochemical control with lower treatment toxicity. We aimed to compare biochemical progression between patients given adjuvant radiotherapy and those given salvage radiotherapy., Methods: We did a phase 3, randomised, controlled, non-inferiority trial across 32 oncology centres in Australia and New Zealand. Eligible patients were aged at least 18 years and had undergone a radical prostatectomy for adenocarcinoma of the prostate with pathological staging showing high-risk features defined as positive surgical margins, extraprostatic extension, or seminal vesicle invasion; had an Eastern Cooperative Oncology Group performance status of 0-1, and had a postoperative prostate-specific antigen (PSA) concentration of 0·10 ng/mL or less. Patients were randomly assigned (1:1) using a minimisation technique via an internet-based, independently generated allocation to either adjuvant radiotherapy within 6 months of radical prostatectomy or early salvage radiotherapy triggered by a PSA of 0·20 ng/mL or more. Allocation sequence was concealed from investigators and patients, but treatment assignment for individual randomisations was not masked. Patients were stratified by radiotherapy centre, preoperative PSA, Gleason score, surgical margin status, and seminal vesicle invasion status. Radiotherapy in both groups was 64 Gy in 32 fractions to the prostate bed without androgen deprivation therapy with real-time review of plan quality on all cases before treatment. The primary endpoint was freedom from biochemical progression. Salvage radiotherapy would be deemed non-inferior to adjuvant radiotherapy if freedom from biochemical progression at 5 years was within 10% of that for adjuvant radiotherapy with a hazard ratio (HR) for salvage radiotherapy versus adjuvant radiotherapy of 1·48. The primary analysis was done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT00860652., Findings: Between March 27, 2009, and Dec 31, 2015, 333 patients were randomly assigned (166 to adjuvant radiotherapy; 167 to salvage radiotherapy). Median follow-up was 6·1 years (IQR 4·3-7·5). An independent data monitoring committee recommended premature closure of enrolment because of unexpectedly low event rates. 84 (50%) patients in the salvage radiotherapy group had radiotherapy triggered by a PSA of 0·20 ng/mL or more. 5-year freedom from biochemical progression was 86% (95% CI 81-92) in the adjuvant radiotherapy group versus 87% (82-93) in the salvage radiotherapy group (stratified HR 1·12, 95% CI 0·65-1·90; p non-inferiority =0·15). The grade 2 or worse genitourinary toxicity rate was lower in the salvage radiotherapy group (90 [54%] of 167) than in the adjuvant radiotherapy group (116 [70%] of 166). The grade 2 or worse gastrointestinal toxicity rate was similar between the salvage radiotherapy group (16 [10%]) and the adjuvant radiotherapy group (24 [14%])., Interpretation: Salvage radiotherapy did not meet trial specified criteria for non-inferiority. However, these data support the use of salvage radiotherapy as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity., Funding: New Zealand Health Research Council, Australian National Health Medical Research Council, Cancer Council Victoria, Cancer Council NSW, Auckland Hospital Charitable Trust, Trans-Tasman Radiation Oncology Group Seed Funding, Cancer Research Trust New Zealand, Royal Australian and New Zealand College of Radiologists, Cancer Institute NSW, Prostate Cancer Foundation Australia, and Cancer Australia., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To implement a system for unsupervised extraction of tumor stage and prognostic data in patients with genitourinary cancers using clinicopathological and radiology text., Methods: A corpus of 1054 electronic notes (clinician notes, radiology reports and pathology reports) was annotated for tumor stage, prostate specific antigen (PSA) and Gleason grade. Annotations from five clinicians were reconciled to form a gold standard dataset. A training dataset of 386 documents was sequestered. The Medtex algorithm was adapted using the training dataset., Results: Adapted Medtex equaled or exceeded human performance in most annotations, except for implicit M stage (F-measure of 0.69 vs 0.84) and PSA (0.92 vs 0.96). Overall Medtex performed with an F-measure of 0.86 compared to human annotations of 0.92. There was significant inter-observer variability when comparing human annotators to the gold standard., Conclusions: The Medtex algorithm performed similarly to human annotators for extracting stage and prognostic data from varied clinical texts., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Androgen-deprivation therapy in patients with prostate cancer who have relapsed with rising prostate-specific antigen concentration only (PSA-only relapse), or with non-curable but asymptomatic disease at diagnosis, could adversely affect quality of life at a time when the disease itself does not. We aimed to compare the effect of immediate versus delayed androgen-deprivation therapy on health-related quality of life over 5 years in men enrolled in the TOAD (Timing of Androgen Deprivation) trial., Methods: This randomised, multicentre, open-label, phase 3 trial done in 29 public and private cancer centres across Australia, New Zealand, and Canada compared immediate with delayed androgen-deprivation therapy in men with PSA-only relapse after definitive treatment, or de-novo non-curable disease. Patients were randomly assigned (1:1) with a database-embedded, dynamically balanced algorithm to immediate androgen-deprivation therapy (immediate therapy group) or to delayed androgen-deprivation therapy (delayed therapy group). Any type of androgen-deprivation therapy was permitted, as were intermittent or continuous schedules. The European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaires QLQ-C30 and PR25 were completed before randomisation, every 6 months for 2 years, and annually for a further 3 years. The primary outcome of the trial, reported previously, was overall survival, with global health-related quality of life at 2 years as a secondary endpoint. Here we report prespecified secondary objectives of the quality-of-life endpoint. Analysis was by intention to treat. Statistical significance was set at p=0·0036. The trial was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12606000301561, and ClinicalTrials.gov, number NCT00110162., Findings: Between Sept 3, 2004, and July 13, 2012, 293 men were recruited and randomly assigned; 151 to the delayed therapy group and 142 to the immediate therapy group. There was no difference between the two groups in global health-related quality of life over 2 years from randomisation. There were no statistically significant differences in global quality of life, physical functioning, role functioning, or emotional functioning, fatigue, dyspnoea, insomnia, or feeling less masculine over the entire 5 years after randomisation. Sexual activity was lower in the immediate therapy group than in the delayed group at 6 and 12 months (at 6 months mean score 29·20 [95% CI 24·59-33·80] in the delayed group vs 10·40 [6·87-13·93] in the immediate group, difference 18·80 [95% CI 13·00-24·59], p<0·0001; at 12 months 28·63 [24·07-33·18] vs 13·76 [9·94-17·59], 14·86 [8·95-20·78], p<0·0001), with the differences exceeding the clinically significant threshold of 10 points until beyond 2 years. The immediate therapy group also had more hormone-treatment-related symptoms at 6 and 12 months (at 6 months mean score 8·48 [95% CI 6·89-10·07] in the delayed group vs 15·97 [13·92-18·02] in the immediate group, difference -7·49 [-10·06 to -4·93], p<0·0001; at 12 months 9·32 [7·59-11·05] vs 17·07 [14·75-19·39], -7·75 [-10·62 to -4·89], p<0·0001), but with differences below the threshold of clinical significance. For the individual symptoms, hot flushes were clinically significantly higher in the immediate group (adjusted proportion 0·31 for delayed therapy vs 0·55 for immediate therapy, adjusted odds ratio 2·87 [1·96-4·21], p<0·0001) over the 5-year period, as were nipple or breast symptoms (0·06 vs 0·14, 2·64 [1·61-4·34], p=0·00013)., Interpretation: Immediate use of androgen-deprivation therapy was associated with early detriments in specific hormone-treatment-related symptoms, but with no other demonstrable effect on overall functioning or health-related quality of life. This evidence can be used to help decision making about treatment initiation for men at this disease stage., Funding: Australian National Health and Medical Research Council and Cancer Councils, The Royal Australian and New Zealand College of Radiologists, Mayne Pharma Australia, Tolmar Australia., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Androgen-deprivation therapy is offered to men with prostate cancer who have a rising prostate-specific antigen after curative therapy (PSA relapse) or who are considered not suitable for curative treatment; however, the optimal timing for its introduction is uncertain. We aimed to assess whether immediate androgen-deprivation therapy improves overall survival compared with delayed therapy., Methods: In this randomised, multicentre, phase 3, non-blinded trial, we recruited men through 29 oncology centres in Australia, New Zealand, and Canada. Men with prostate cancer were eligible if they had a PSA relapse after previous attempted curative therapy (radiotherapy or surgery, with or without postoperative radiotherapy) or if they were not considered suitable for curative treatment (because of age, comorbidity, or locally advanced disease). We used a database-embedded, dynamically balanced, randomisation algorithm, coordinated by the Cancer Council Victoria, to randomly assign participants (1:1) to immediate androgen-deprivation therapy (immediate therapy arm) or to delayed androgen-deprivation therapy (delayed therapy arm) with a recommended interval of at least 2 years unless clinically contraindicated. Randomisation for participants with PSA relapse was stratified by type of previous therapy, relapse-free interval, and PSA doubling time; randomisation for those with non-curative disease was stratified by metastatic status; and randomisation in both groups was stratified by planned treatment schedule (continuous or intermittent) and treatment centre. Clinicians could prescribe any form and schedule of androgen-deprivation therapy and group assignment was not masked. The primary outcome was overall survival in the intention-to-treat population. The trial closed to accrual in 2012 after review by the independent data monitoring committee, but data collection continued for 18 months until Feb 26, 2014. It is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12606000301561) and ClinicalTrials.gov (NCT00110162)., Findings: Between Sept 3, 2004, and July 13, 2012, we recruited 293 men (261 with PSA relapse and 32 with non-curable disease). We randomly assigned 142 men to the immediate therapy arm and 151 to the delayed therapy arm. Median follow-up was 5 years (IQR 3·3-6·2) from the date of randomisation. 16 (11%) men died in the immediate therapy arm and 30 (20%) died in the delayed therapy arm. 5-year overall survival was 86·4% (95% CI 78·5-91·5) in the delayed therapy arm versus 91·2% (84·2-95·2) in the immediate therapy arm (log-rank p=0·047). After Cox regression, the unadjusted HR for overall survival for immediate versus delayed arm assignment was 0·55 (95% CI 0·30-1·00; p=0·050). 23 patients had grade 3 treatment-related adverse events. 105 (36%) men had adverse events requiring hospital admission; none of these events were attributable to treatment or differed between treatment-timing groups. The most common serious adverse events were cardiovascular, which occurred in nine (6%) patients in the delayed therapy arm and 13 (9%) in the immediate therapy arm., Interpretation: Immediate receipt of androgen-deprivation therapy significantly improved overall survival compared with delayed intervention in men with PSA-relapsed or non-curable prostate cancer. The results provide benchmark evidence of survival rates and morbidity to discuss with men when considering their treatment options., Funding: Australian National Health and Medical Research Council and Cancer Councils, The Royal Australian and New Zealand College of Radiologists, Mayne Pharma Australia., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: We tested the ability of the Assessment of New Radiation Oncology Technology and Treatments framework to determine the clinical efficacy and safety of intensity-modulated radiation therapy (IMRT) compared with 3-dimensional radiation therapy (3DCRT) for post-prostatectomy radiation therapy (PPRT) to support its timely health economic evaluation., Methods: Treatment plans produced using FROGG guidelines provided dosimetry parameters for both techniques at 64 Gy and 70 Gy and were also used to model early and late outcome probabilities. Clinical parameters were derived from early toxicity and quality of life patient data, systematic literature review and expert opinion. Dosimetry parameters were correlated with the measures of clinical efficacy and safety., Results: Data from two patient cohorts (29 and 27 respectively) were collected within the project timeframe, providing evidence for acute toxicity and quality of life, and dosimetric comparisons. Relative rates of tumour control probability (TCP) and normal tissue control probability (NTCP) modelling were readily derived from the planning exercise and demonstrated advantages in uncomplicated TCP for IMRT over 3DCRT, predominantly due to normal tissue sparing. The safety of IMRT delivery was demonstrated with TCP uncompromised by IMRT protocol violations, which achieved rectal sparing only by reducing minimum target dose and coverage., Conclusion: Sources of desk-top and patient-based evidence were successfully used to demonstrate potential improved clinical efficacy and safety of applying dose escalation using IMRT instead of 3DCRT in PPRT., (© 2015 The Royal Australian and New Zealand College of Radiologists.)

In many areas of health care, practice standards have become an accepted method for professions to assess and improve the quality of care delivery. The aim of this work is to present the development of practice standards for radiation oncology in Australia, highlighting critical points and lessons learned. Following a review of radiotherapy services in Australia, a multidisciplinary group with support from the Australian Government developed practice standards for radiation oncology in Australia. The standards were produced in a multistep process including a nationwide survey of radiotherapy centres and piloting of the standards in a representative subset of all Australian radiotherapy centres. The standards are grouped into three sections: Facility management (covering staffing, data management, equipment and processes); Treatment planning and delivery (providing more detailed guidance on prescription, planning and delivery); Safety and quality management (including radiation safety, incident monitoring and clinical trials participation). Each of the 16 standards contains specific criteria, a commentary and suggestions for the evidence required to demonstrate compliance. The development of the standards was challenging and time consuming, but the collaborative efforts of the professions resulted in standards applicable throughout Australia and possibly further afield., (Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Introduction: The study aim was to develop a generic framework to derive the parameters to populate health-economic models for the rapid evaluation of new techniques and technologies in radiation oncology., Methods: A draft framework was developed through horizon scanning for relevant technologies, literature review to identify framework models, and a workshop program with radiation oncology professionals, biostatisticians, health economists and consumers to establish the Framework's structure. It was tested using four clinical protocols, comparing intensity modulated with 3D conformal therapy (post-prostatectomy, anal canal and nasopharynx) and image-guided radiation therapy techniques with off-line review of portal imaging (in the intact prostate)., Results: The draft generic research framework consisted of five sequential stages, each with a number of components, and was assessed as to its suitability for deriving the evidence needed to populate the decision-analytic models required for the health-economic evaluations. A final Framework was established from this experience for use by future researchers to provide evidence of clinical efficacy and cost-utility for other novel techniques. The four clinical treatment sites tested during the project were considered suitable to use in future evaluations., Conclusions: Development of a generic research framework to predict early and long-term clinical outcomes, combined with health-economic data, produced a generally applicable method for the rapid evaluation of new techniques and technologies in radiation oncology. Its application to further health technology assessments in the radiation oncology sector will allow further refinement and support its generalisability., (© 2014 The Royal Australian and New Zealand College of Radiologists.)

Objectives: To assess the tolerability and survival outcome of curative radiotherapy in patients over the age of 85 years., Design, Setting, and Participants: Retrospective analysis of all patients aged over 85 years who received radiotherapy as part of curative treatment for any cancer (excluding insignificant skin cancers) at the Peter MacCallum Cancer Centre between 1 January 2000 and 1 January 2010., Main Outcome Measures: Poor treatment tolerability (defined as hospital admission during radiotherapy, treatment break, or early treatment cessation); predictors for poor treatment tolerability, overall survival and cancer-specific survival., Results: 327 treatment courses met eligibility criteria. The median age of patients was 87 years. The most common treatment sites were pelvis (30%), head and neck (25%), and breast (18%). The Eastern Cooperative Oncology Group performance status (ECOG PS) score was 0 or 1 for 70% of patients. Overall, 79% of patients completed the prescribed treatment without poor treatment tolerability, and 95% of patients completed all treatment. Only unfavourable ECOG PS score (odds ratio [OR], 1.80; P = 0.005) and increasing age (OR, 1.18; P = 0.018) predicted poor treatment tolerability. ECOG PS score predicted overall survival (hazard ratio, 1.53; P = 0.001)., Conclusion: Age should not be the sole discriminator in decisions to prescribe aggressive loco-regional radiotherapy. ECOG PS score predicts for treatment tolerability, and also overall survival. The risk of cancer death was higher than non-cancer death for more than 5 years after treatment.

Objective: To outline the development of the 'Timing of Androgen Deprivation' (TOAD) protocol, a collaborative randomised clinical trial under the auspices of the Cancer Council Victoria, the Trans-Tasman Radiation Oncology Group, and the Urological Society of Australia and New Zealand (USANZ), which opened to recruitment in 2004., Patients and Methods: The principal hypothesis for the trial was that the early introduction of androgen-deprivation therapy (ADT; experimental arm) at the time when curative therapies are no longer considered an option, would improve overall survival for these patients, whilst maintaining an acceptable quality of life; compared with waiting for disease progression or the development of symptoms (control arm). An increase in overall survival at 5 years of 10% was judged to be clinically worthwhile., Results: Recruitment was slow, with fewer than half of the protocol requirement of 750 patients eventually accrued, but nonetheless it is considered that the trial will still contribute a major source of evidence in this area. The study closed to follow-up at the end of 2013, with data analysis commencing mid-2014, and with the primary publication anticipated to be submitted by the end of 2014., Conclusion: The question of timing of ADT remains relevant in the current era of newer and more varied treatment methods. Even with the advent of novel chemotherapy and the biological agents that are undergoing investigation for progressively earlier disease stages, the dilemma of when to commence palliative treatment in an asymptomatic patient will remain, unless or until these agents are shown to increase overall survival. The TOAD trial will contribute to answering at least in part, some of these questions., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objectives: To test the hypothesis that observation with early salvage radiotherapy (SRT) is not inferior to 'standard' treatment with adjuvant RT (ART) with respect to biochemical failure in patients with pT3 disease and/or positive surgical margins (SMs) after radical prostatectomy (RP). To compare the following secondary endpoints between the two arms: patient-reported outcomes, adverse events, biochemical failure-free survival, overall survival, disease-specific survival, time to distant failure, time to local failure, cost utility analysis, quality adjusted life years and time to androgen deprivation., Patients and Methods: The Radiotherapy - Adjuvant Versus Early Salvage (RAVES) trial is a phase III multicentre randomised controlled trial led by the Trans Tasman Radiation Oncology Group (TROG), in collaboration with the Urological Society of Australia and New Zealand (USANZ), and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). In all, 470 patients are planned to be randomised 1:1 to either ART commenced at ≤4 months of RP (standard of care) or close observation with early SRT triggered by a PSA level of >0.20 ng/mL (experimental arm). Eligible patients have had a RP for adenocarcinoma of the prostate with at least one of the following risk factors: positive SMs ± extraprostatic extension ± seminal vesicle involvement. The postoperative PSA level must be ≤0.10 ng/mL. Rigorous investigator credentialing and a quality assurance programme are designed to promote consistent RT delivery among patients., Results: Trial is currently underway, with 258 patients randomised as of 31 October 2013. International collaborations have developed, including a planned meta-analysis to be undertaken with the UK Medical Research Council/National Cancer Institute of Canada Clinical Trials Group RADICALS (Radiotherapy and Androgen Deprivation In Combination with Local Surgery) trial and an innovative psycho-oncology sub-study to investigate a patient decision aid resource., Conclusion: On the current evidence available, it remains unclear if ART is equivalent or superior to observation with early SRT., (© 2014 The Authors. BJU International © 2014 BJU International.)

Purpose: Low-dose-rate brachytherapy using iodine-125 seeds is a highly efficacious treatment for low-risk prostate cancer. We propose a bioeffect model may be used to target an ablative dose to the tumor with a lower, therapeutic dose to low-risk regions to maintain high rates of tumor control with reduced toxicity. We report on the validation of the model and derivation of the optimal cutpoint value of tumor control probability (TCP) that predicts for freedom from biochemical failure., Methods and Materials: The TCP was calculated from postimplant dosimetry data for 423 prostate cancer patients from three Australian institutions. To apply the model, the prostate was mathematically divided into 12 subsections with tumor characteristics, including a nonuniform distribution of tumor cell density, derived from the literature., Results: When TCP values were above and below 0.62, the 5-year freedom from biochemical failure were 93.7% (95% confidence interval [CI], 90.4, 96.4%) and 88.8% (95% confidence interval, 81.3, 94.5%), respectively (p = 0.004)., Conclusions: Using postimplant dosimetry data, the TCP model was able to predict for freedom from biochemical failure. The cutpoint value that would be used clinically depends on the selection of the model parameters, but the potential for the model to be used in the optimization of treatment planning is demonstrated., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Introduction: We present the results of a pilot study to test the feasibility of a brachytherapy dosimetry audit., Methods: The feasibility study was conducted at seven sites from four Australian states in both public and private centres. A purpose-built cylindrical water phantom was imaged using the local imaging protocol and a treatment plan was generated to deliver 1 Gy to the central (1 of 3) thermoluminescent dosimeter (TLD) from six dwell positions., Results: All centres completed the audit, consisting of three consecutive irradiations, within a 2-h time period, with the exception of one centre that uses a pulsed dose rate brachytherapy unit. All TLD results were within 4.5% of the predicted value, with the exception of one subset where the dwell position step size was incorrectly applied., Conclusions: While the limited data collected in the study demonstrated considerable heterogeneity in clinical practice, the study proved a brachytherapy dosimetry audit to be feasible. Future studies should include verification of source strength using a Standard Dosimetry Laboratory calibrated chamber, a phantom that more closely mimics the clinical situation, a more comprehensive review of safety and quality assurance (QA) procedures including source dwell time and position accuracy, and a review of patient treatment QA procedures such as applicator position verification., (© 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.)

Objective: This paper aims to describe 'Cognitive Existential Couple Therapy' (CECT), a novel couples-based intervention for men with early stage prostate cancer (PCa) and their partners, and to report preliminary findings from a pilot study that investigated the acceptability and feasibility of the intervention and the measures to be used in a subsequent randomised controlled trial., Methods: A manualised CECT programme was delivered to 12 couples facing a diagnosis of PCa within the previous 12 months by psychiatrists and clinical psychologists. Participants completed measures of psychological distress, marital function and coping pattern before and after CECT. Semi-structured interviews were conducted with nine couples shortly after the completion of CECT., Results: The application of CECT was both feasible and acceptable as indicated by favourable participant compliance (10 of the 12 couples attended all six designated sessions), completion of measures before and after CECT and participation in semi-structured interviews by nine couples. Preliminary results included reduced levels of avoidance and hyperarousal after the programme, with this effect stronger in partners than in patients. Interviews demonstrated that couples valued the therapist's contribution to their overall care., Conclusions: Previous research suggests that a couple-focused psychological intervention is desirable in the context of early stage PCa. This pilot study has established that CECT is acceptable, feasible and valued by couples facing a recent PCa diagnosis and demonstrates a potential for reduced psychological distress following CECT. A randomised controlled trial is currently being undertaken to validate the efficacy of this novel approach., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objectives: To report on complications from transrectal ultrasound-guided insertion of fiducial markers for prostate image-guided radiotherapy., Methods: 234 patients who underwent transrectal fiducial marker insertion for prostate cancer image-guided radiotherapy were assessed retrospectively by questionnaire with regard to the duration and severity of eight symptoms experienced following the procedure. Pain during the implantation procedure was assessed according to the Wong-Baker faces pain scale., Results: Of 234 patients, 32% had at least one new symptom after the procedure. The commonest new symptom following the procedure was urinary frequency affecting 16% of patients who had not been troubled by frequency beforehand. Haematuria, rectal bleeding, dysuria and haematospermia affected 9-13% of patients, mostly at Grade 1 or 2. Pain, obstruction, and fever and shivers affected 3-4% of patients. Grade 3 rectal bleeding, haematuria, fever and shivers, and urinary frequency affected 0.5-1.5% of patients. Only one patient had a Grade 4 complication (i.e. fever and shivers). Overall, 9% of patients had symptoms lasting more than 2 weeks. The commonest symptoms that lasted more than 2 weeks were frequency, dysuria, obstructive symptoms and rectal bleeding. Mean pain score during the procedure was 1.1 (range 0-5)., Conclusion: Transrectal ultrasound-guided fiducial marker insertion for image-guided radiotherapy is well tolerated in the majority of prostate cancer patients. Most symptoms were Grade 1 or 2 in severity. Symptoms in the majority of patients last under 2 weeks. The most serious complication was sepsis in our study.

Purpose: There are multiple treatment options for favorable-risk prostate cancer. High-dose-rate (HDR) brachytherapy as a monotherapy is appealing, but its use is still investigational. A Phase II trial was undertaken to explore the value of such treatment in low-to-intermediate risk prostate cancer., Methods and Materials: This was a single-institution, prospective study. Eligible patients had low-risk prostate cancer features but also Gleason scores of 7 (51% of patients) and stage T2b to T2c cancer. Treatment with HDR brachytherapy with a single implant was administered over 2 days. One of four fractionation schedules was used in a dose escalation study design: 3 fractions of 10, 10.5, 11, or 11.5 Gy. Patients were assessed with the Common Terminology Criteria for Adverse Events version 2.0 for urinary toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring schema for rectal toxicity, and the Expanded Prostate Cancer Index Composite (EPIC) questionnaire to measure patient-reported health-related quality of life. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml., Results: Between 2003 and 2008, 79 patients were enrolled. With a median follow-up of 39.5 months, biochemical relapse occurred in 7 patients. Three- and 5-year actuarial biochemical control rates were 88.4% (95% confidence interval [CI], 78.0-96.2%) and 85.1% (95% CI, 72.5-94.5%), respectively. Acute grade 3 urinary toxicity was seen in only 1 patient. There was no instance of acute grade 3 rectal toxicity. Rates of late grade 3 rectal toxicity, dysuria, hematuria, urinary retention, and urinary incontinence were 0%, 10.3%, 1.3%, 9.0%, and 0%, respectively. No grade 4 or greater toxicity was recorded. Among the four (urinary, bowel, sexual, and hormonal) domains assessed with the EPIC questionnaire, only the sexual domain did not recover with time., Conclusions: HDR brachytherapy as a monotherapy for favorable-risk prostate cancer, administered using a single implant over 2 days, is feasible and has acceptable acute and late toxicities. Further follow-up is still required to better evaluate the efficacy of such treatment., (Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.)

Purpose: To benchmark the dosimetric quality assessment of prostate intensity-modulated radiotherapy and determine whether the quality is influenced by disease or treatment factors., Patients and Methods: We retrospectively analyzed the data from 155 consecutive men treated radically for prostate cancer using intensity-modulated radiotherapy to 78 Gy between January 2007 and March 2009 across six radiotherapy treatment centers. The plan quality was determined by the measures of coverage, homogeneity, and conformity. Tumor coverage was measured using the planning target volume (PTV) receiving 95% and 100% of the prescribed dose (V(95%) and V(100%), respectively) and the clinical target volume (CTV) receiving 95% and 100% of the prescribed dose. Homogeneity was measured using the sigma index of the PTV and CTV. Conformity was measured using the lesion coverage factor, healthy tissue conformity index, and the conformity number. Multivariate regression models were created to determine the relationship between these and T stage, risk status, androgen deprivation therapy use, treatment center, planning system, and treatment date., Results: The largest discriminatory measurements of coverage, homogeneity, and conformity were the PTV V(95%), PTV sigma index, and conformity number. The mean PTV V(95%) was 92.5% (95% confidence interval, 91.3-93.7%). The mean PTV sigma index was 2.10 Gy (95% confidence interval, 1.90-2.20). The mean conformity number was 0.78 (95% confidence interval, 0.76-0.79). The treatment center independently influenced the coverage, homogeneity, and conformity (all p < .0001). The planning system independently influenced homogeneity (p = .038) and conformity (p = .021). The treatment date independently influenced the PTV V(95%) only, with it being better at the start (p = .013). Risk status, T stage, and the use of androgen deprivation therapy did not influence any aspect of plan quality., Conclusion: Our study has benchmarked measures of coverage, homogeneity, and conformity for the treatment of prostate cancer using IMRT. The differences seen between centers and planning systems and the coverage deterioration over time highlight the need for every center to determine their own benchmarks and apply clinical vigilance with respect to maintaining these through quality assurance., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Image-guided radiotherapy (IGRT) increases the accuracy of treatment delivery through daily target localisation. We report on toxicity symptoms experienced during radiotherapy treatment, with and without IGRT in prostate cancer patients treated radically., Methods: Between 2006 and 2009, acute toxicity data for ten symptoms were collected prospectively onto standardized assessment forms. Toxicity was scored during radiotherapy, according to the Common Terminology Criteria Adverse Events V3.0, for 275 prostate cancer patients before and after the implementation of a fiducial marker IGRT program and dose escalation from 74 Gy in 37 fractions, to 78 Gy in 39 fractions. Margins and planning constraints were maintained the same during the study period. The symptoms scored were urinary frequency, cystitis, bladder spasm, urinary incontinence, urinary retention, diarrhoea, haemorrhoids, proctitis, anal skin discomfort and fatigue. Analysis was conducted for the maximum grade of toxicity and the median number of days from the onset of that toxicity to the end of treatment., Results: In the IGRT group, 14228 toxicity scores were analysed from 249 patients. In the non-IGRT group, 1893 toxicity scores were analysed from 26 patients. Urinary frequency ≥G3 affected 23% and 7% in the non-IGRT and IGRT group respectively (p = 0.0188). Diarrhoea ≥G2 affected 15% and 3% of patients in the non-IGRT and IGRT groups (p = 0.0174). Fatigue ≥G2 affected 23% and 8% of patients in the non-IGRT and IGRT groups (p = 0.0271). The median number of days with a toxicity was higher for ≥G2 (p = 0.0179) and ≥G3 frequency (p = 0.0027), ≥G2 diarrhoea (p = 0.0033) and ≥G2 fatigue (p = 0.0088) in the non-IGRT group compared to the IGRT group. Other toxicities were not of significant statistical difference., Conclusions: In this study, prostate cancer patients treated radically with IGRT had less severe urinary frequency, diarrhoea and fatigue during treatment compared to patients treated with non-IGRT. Onset of these symptoms was earlier in the non-IGRT group. IGRT results in less acute toxicity during radiotherapy in prostate cancer.

We discuss the relevance of current trends in clinical trial conduct in light of the burgeoning need to underpin our practice with evidence, the contribution of novel imaging approaches to provide acceptable surrogate endpoints of effect and their place in the individualised medicine of the future., (© 2011 The Authors. Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists.)

Purpose: To report long-term outcomes for treatment of prostate cancer using dose escalation with high-dose-rate (HDR) brachytherapy and 3-dimensional conformal external beam radiotherapy (3DCRT), and compare them with outcomes for treatment of prostate cancer with 3DCRT alone at the same institution., Methods and Materials: From 1998 to 2003, 587 patients were treated for clinically localized prostate cancer. Patients received either 3DCRT (median, 46Gy) with a single HDR brachytherapy implant (196 patients) delivering a fractionated dose of 18Gy (combined group) or 3DCRT (median, 70Gy; 387 patients; "3DCRT alone"). There were 41.9% patients with intermediate-risk and 42.6% with high-risk disease. In all, 441 patients (75.1%) received neoadjuvant and 116 patients (19.8%) received adjuvant androgen deprivation therapy. The American Society of Therapeutic Radiology and Oncology Phoenix definition for biochemical failure was used., Results: The median followup was 5.5 years. The 5- and 7-year biochemical control (BC) rates were 82.5% and 80.3%, respectively, for the combined group and 81.3% and 71%, respectively, for 3DCRT alone; for overall survival, they were 91.9% and 89.5% vs. 88.7% and 86.2%, respectively, whereas for cause-specific survival, they were 96.9% and 96.1% vs. 97.6% and 96.2%, respectively. Cox proportional hazard regression analysis for BC revealed that low Gleason grade, HDR brachytherapy combined with 3DCRT, and adjuvant androgen deprivation therapy were significant in predicting BC. Radiation Therapy Oncology Group Grade 3 late urinary and rectal morbidity rates were 7.1% and 0%, respectively. No Grade > or =4 reactions were detected., Conclusions: HDR brachytherapy combined with 3DCRT was associated with improved BC and minimal toxicity in patients with unfavorable prostate cancer compared with conventional 3DCRT., (Copyright (c) 2010 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

The kidneys are dose-limiting organs in abdominal radiotherapy. Kilovoltage (kV) radiographs can be acquired using on-board imager (OBI)-equipped linear accelerators with better soft tissue contrast and lower radiation doses than conventional portal imaging. A feasibility study was conducted to test the suitability of anterior-posterior (AP) non-contrast kV radiographs acquired at treatment time for online kidney position verification. Anthropomorphic phantoms were used to evaluate image quality and radiation dose. Institutional Review Board approval was given for a pilot study that enrolled 5 adults and 5 children. Customized digitally reconstructed radiographs (DRRs) were generated to provide a priori information on kidney shape and position. Radiotherapy treatment staff performed online evaluation of kidney visibility on OBI radiographs. Kidney dose measured in a pediatric anthropomorphic phantom was 0.1 cGy for kV imaging and 1.7 cGy for MV imaging. Kidneys were rated as well visualized in 60% of patients (90% confidence interval, 34-81%). The likelihood of visualization appears to be influenced by the relative AP separation of the abdomen and kidneys, the axial profile of the kidneys, and their relative contrast with surrounding structures. Online verification of kidney position using AP non-contrast kV radiographs on an OBI-equipped linear accelerator appears feasible for patients with suitable abdominal anatomy. Kidney position information provided is limited to 2-dimensional "snapshots," but this is adequate in some clinical situations and potentially advantageous in respiratory-correlated treatments. Successful clinical implementation requires customized partial DRRs, appropriate imaging parameters, and credentialing of treatment staff.

Purpose: To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma., Methods and Materials: Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0., Results: At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n=15) or optical urethrotomy (n=20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p=0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p=0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p=0.008)., Conclusions: BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.

Purpose: To define and incorporate the impact of the percentage of positive biopsy cores (PPC) into a predictive model of prostate cancer radiotherapy biochemical outcome., Methods and Materials: The data of 3264 men with clinically localized prostate cancer treated with external beam radiotherapy at four institutions were retrospectively analyzed. Standard prognostic and treatment factors plus the number of biopsy cores collected and the number positive for malignancy by transrectal ultrasound-guided biopsy were available. The primary endpoint was biochemical failure (bF, Phoenix definition). Multivariate proportional hazards analyses were performed and expressed as a nomogram and the model's predictive ability assessed using the concordance index (c-index)., Results: The cohort consisted of 21% low-, 51% intermediate-, and 28% high-risk cancer patients, and 30% had androgen deprivation with radiotherapy. The median PPC was 50% (interquartile range [IQR] 29-67%), and median follow-up was 51 months (IQR 29-71 months). Percentage of positive biopsy cores displayed an independent association with the risk of bF (p=0.01), as did age, prostate-specific antigen value, Gleason score, clinical stage, androgen deprivation duration, and radiotherapy dose (p<0.001 for all). Including PPC increased the c-index from 0.72 to 0.73 in the overall model. The influence of PPC varied significantly with radiotherapy dose and clinical stage (p=0.02 for both interactions), with doses<66 Gy and palpable tumors showing the strongest relationship between PPC and bF. Intermediate-risk patients were poorly discriminated regardless of PPC inclusion (c-index 0.65 for both models)., Conclusions: Outcome models incorporating PPC show only minor additional ability to predict biochemical failure beyond those containing standard prognostic factors.

Background: To examine the long-term morbidity of high dose rate brachytherapy boost (HDRBB) in prostate cancer., Patients and Methods: A phase I/II HDRBB dose escalation protocol recruited 108 men up to November 1999. Treatment combined 46 Gy external beam radiation to the prostate with four fractions of HDR totalling 16 or 20 Gy. Morbidity data were collected prospectively regarding urological, bowel and erectile dysfunction (ED) symptoms using a validated clinician completed instrument. Actuarial incidence and prevalence of symptoms were estimated; the latter to account for potential recovery., Results: The median follow-up was 78 months, with 880 questionnaires completed. The respective actuarial cumulative incidence and point prevalence rates of any grade 2 or higher symptom score at 5 years were 24.9% (95% confidence intervals [CI] 16.8-33.5%) and 7.7% (95% CI 1.8-14.5%) for urinary toxicity; and 11.3% (95% CI 5.6-17.1%) and 3.0% (0-7.6%) for rectal toxicity, meaning that most symptom sub-domains showed substantial recovery with time. Corresponding erectile function toxicity figures for the subgroup of men (n=53) with normal erectile function prior to treatment and no androgen deprivation therapy were 77.0% (95% CI 64.9-88.1%) and 45.3% (95% CI 27.2-64.6%). Some late toxicity profiles developed after twelve months, typically with low grade bowel and urinary urgency. These peaked at 12-24 months and stayed relatively stable subsequently. Paradoxically, grade 1 or more nocturia symptoms settle with time, despite the accumulation of grade 2 or more toxicity beyond 24 months., Conclusions: HDRBB as a means of dose escalation in prostate cancer is associated with low and relatively stable rates of long-term bowel and urinary morbidity, and compares favourably with external beam results. Actuarial incidence methods overstate the burden of toxicity with substantial recovery noted in most domains.

Purpose: To examine the effect of fraction size and total dose of radiation on recurrence of localized prostate cancer., Methods and Materials: A total of 3756 patients treated with radiation monotherapy at three institutions were analyzed, including 185 high-dose-rate brachytherapy (HDRB) boost patients. The 5th to 95th centiles of external beam radiotherapy (EBRT) fraction sizes and doses were 1.8 to 2.86 Gy, and 57.4 to 77.4 Gy, respectively, and HDRB fractional doses were between 5.5 and 12 Gy, totaling 147 unique fractionation schedules. Failure was defined by one biochemical (nadir + 2 ng/ml) and two advanced disease endpoints. The alpha/beta ratios were estimated via a proportional hazards model stratified by risk severity and institution., Results: The alpha/beta ratio using biochemical recurrence was 3.7 Gy (95% confidence interval [95% CI], 1.1, infinity Gy) for EBRT-only cases and 2.6 Gy (95% CI, 0.9, 4.8 Gy) after the addition of HDRB data. This estimate was highly dependent on an HDRB homogeneity correction factor (120% HDRB dose increase; alpha/beta ratio 4.5 Gy, 95% CI 1.6, 8.7 Gy). A 5-Gy increase in total dose reduced the hazard of failure by 16% (95% CI 11, 21%, p < 0.0001), and had more impact as follow-up matured (p < 0.0003). The clinically advanced endpoints concurred with the biochemical failure results, albeit with less precision., Conclusions: This study supports the concept that the alpha/beta ratio of prostate cancer is low, although considerable uncertainty remains in the estimated value. Outcome data from EBRT studies using substantially higher doses per fraction are needed to show increased precision in these estimates.

Advances in prostate cancer treatments since the 1990s have led to a growing proportion of patients living with the effects of the cancer. Various challenges face the man and his partner from the point of learning of the diagnosis: deciding among numerous diverse treatment options, dealing with side-effects of treatment and possibly facing the terminal phase of the illness. This invariably has an impact on the patient's family and, in view of the older age group of men usually affected, the experience of a partner is particularly relevant. A thorough review of the research literature reporting directly from partners of prostate cancer patients has not been undertaken previously. For this review, five databases were searched for the decade 1994-2005, during which most of the work in this field has been done. Very few evaluations of psychosocial interventions involving the partner were found, but there was a preponderance of qualitative studies involving small numbers of participants and quantitative surveys with little consistency in the measures used. The literature suggests that partners report more distress than patients, yet believe that patients are the more distressed, and the focus of concern of patients on their sexual function is not shared to an equal degree by their partners.

Purpose: The study aimed to evaluate mature outcomes of a Phase I/II high-dose-rate brachytherapy (HDRB) boost protocol., Methods and Materials: We analyzed data from 88 patients with T1a-T3a, N0, M0 prostate adenocarcinoma treated on a prospective Phase I/II HDRB boost protocol of 16 (n = 47) or 20 Gy (n = 41) in four fractions, without planned androgen deprivation therapy. HDRB was added to 46 Gy of external beam radiotherapy (EBRT). Outcomes were compared to a contemporaneous retrospective cohort of 104 patients receiving 66 Gy EBRT monotherapy. The primary endpoint was freedom from biochemical failure, defined as a 2 ng/mL rise above the lowest prostate-specific antigen (PSA) (FFbFn2), whereas the American Society of Therapeutic Radiology and Oncology consensus definition (ACD) was used for comparative purposes., Results: For the HDRB cohort, the overall actuarial 5-year FFbFn2 was 67.4% (95% CI: 58.2-75.5%). For the HDRB doses of 16 and 20 Gy, the 5-year FFbFn2 rates were 58.8% (95% CI: 41.9-72.5%) and 77.3% (95% CI: 64.4-88.3%), respectively (log-rank test p = 0.07). Compared to men treated with 66 Gy EBRT, using multivariate analysis, there was no significant benefit to using HDRB with the FFbFn2 outcome (p = 0.52), yet the ACD suggested a significant advantage (hazard ratio 0.50, 95% CI: 0.29-0.86, p = 0.011). There was a trend to better FFbFn2 outcomes with increasing biologically effective doses (p = 0.09), which was significant using the ACD (p = 0.0003)., Conclusions: The data support HDRB boost as a potential means of dose escalation in prostate cancer. Significant findings using the ACD need to be validated with contemporary biochemical failure definitions. Prospective trials to optimize fractionation and evaluate outcomes in comparison to contemporary EBRT techniques are warranted.

Background and Purpose: To determine the feasibility, toxicity, and clinical effectiveness of concurrent weekly cisplatin chemotherapy in conjunction with definitive radiation in the treatment of localised muscle invasive bladder cancer., Patients and Methods: In January 1997 the Trans Tasman Radiation Oncology Group embarked on a Phase II study (TROG 97.01) of weekly cisplatin (35 mg/m(2) x 7 doses) plus radiation to a dose of 63 Gy over 7 weeks. Following an interim toxicity analysis, the dose intensity of cisplatin was reduced to 6 cycles and the radiation schedule changed to 64 Gy over 6.5 weeks leading to the second study (TROG 99.06). A total of 113 patients were enrolled., Results: Acute grade 3 urinary toxicity occurred in 23% of the patients. Acute grade 4 pelvic toxicity was not seen. Thirty-eight patients (33%) experienced grade 3 or 4 cisplatin related toxicities with 15 patients (12%) requiring significant dose modification. The reduced dose intensity in Study 99.06 improved tolerability. Incidence of significant late morbidity was low (6%). Seventy-nine patients (70%) achieved complete remission at the 6 month cystoscopic assessment. Local invasive recurrence was seen in 11 of the 79 patients (14%). In 18 patients (16%) isolated superficial TCC/CIS were detected (6 months and beyond). The local control rate was 45% with a functional bladder being retained in 69 of the 113 patients (61%). RFS and DSS at 5 years were 33% and 50%, respectively., Conclusion: Our two sequential Phase II studies have shown that concurrent chemoradiation using weekly cisplatin in the management of localised invasive bladder TCC is feasible and reasonably well tolerated. This approach is currently being investigated further in a randomised study.

Purpose: To evaluate the impact of an alternative biochemical failure (bF) definition on the performance of existing plus de novo prognostic models., Methods and Materials: The outcomes data of 1,458 Australian and 703 Canadian men treated with external-beam radiation monotherapy between 1993 and 1997 were analyzed using a lowest prostate-specific antigen (PSA) level to date plus 2 ng/mL (L + 2) bF definition. Two existing prognostic models were scrutinized using discrimination (Somers Dxy [SDxy]) and calibration indices. Alternative prognostic models were also created using recursive partitioning analysis (RPA) and multivariate nomogram methods for comparison., Results: Discrimination of bF was improved using the L + 2 definition compared with the American Society for Therapeutic Radiology and Oncology (ASTRO) definition using both the three-level risk model (SDxy 0.30 and 0.22, respectively) or the nomogram (SDxy 0.35 and 0.27, respectively). Both existing prognostic models showed only modest calibration accuracy. Using RPA, five distinct risk groups were identified based primarily on Gleason score (GS) and all subsequent divisions based on PSA. All GS 7-10 tumors were intermediate or high risk. This model and the developed nomogram showed improved discrimination over the existing models as well as accurate calibration against the Canadian data, apart from the 30-50% failure region., Conclusions: The L + 2 definition of bF provides improved capacity for discrimination of failure risk. New prognostic models based on this endpoint have overall statistical performance superior to those based on the ASTRO consensus definition but continue to have unreliable discrimination in the intermediate-risk region.

Purpose: To investigate the variability of prostate implant quality indices between three different methods of calculating the post-implant dose distribution., Methods and Materials: In a study of 9 permanent prostate implant patients, post-implant dosimetry was carried out using three methods of identifying seed positions within the prostate volume: (1) prostate volumes defined by transrectal ultrasound (TRUS) immediately following implant were registered with shift-film defined seed positions, (2) seeds were identified directly from the post-implant TRUS images, and (3) CT was used to define seed positions and prostate volumes from images acquired at 41-65 days post-implant. For each method, the volume of prostate receiving 90%, 100%, and 150% of the prescribed dose (V90, V100, V150) and the dose delivered to 90% of the prostate volume (D90) were calculated., Results: Post-implant TRUS volumes were within 15% of the preimplant TRUS volumes in 8 of the 9 patients investigated. The post-implant CT volume was within 15% of the preimplant (TRUS) volume in only 3 of the 9 cases. The value of the dosimetry parameters was dependent on the method used and varied by 5-25% for V90, 5-30% for V100, 42-134% for V150, and 9-60% for D90. No simple relationship was found between change in volume and the resultant change in dosimetry parameter. Differences in dosimetry parameters due to source localization uncertainties was found to be small (< or = 10% for V100) when comparing methods (1) and (2)., Conclusions: There are many uncertainties in the calculation of parameters that are commonly used to describe the quality of a permanent prostate implant. Differences in the parameters calculated were most likely a result of a combination of factors including uncertainties in delineating the prostate with different imaging modalities, differences in source identification techniques, and intraobserver variability.

Purpose: To assess the impact of pretreatment prognostic factors plus subsequent biochemical failure on overall survival after radiotherapy for prostate cancer., Methods and Materials: We analyzed the prostate-specific antigen (PSA) and survival records of 1571 men with clinically localized prostate cancer treated with external beam radiotherapy monotherapy at the former Queensland Radium Institute between 1990 and 1997. The pretreatment PSA level, biopsy Gleason score, clinical stage, patient age, and the development of biochemical failure were assessed in relationship to overall survival and cause-specific survival, using fixed, as well as time-dependent, statistics., Results: The median follow-up was 88.1 months (95 months for those still alive). The actuarial overall survival, cause-specific survival, and biochemical failure-free survival rate at 10 years was 61.1%, 80.9%, and 25.9% respectively. Cause-specific survival was independently influenced by the pretreatment PSA level, Gleason score, clinical stage, and the development of biochemical failure (relative risk, 19.1). Using the overall survival endpoint, multivariate analysis showed age, pretreatment PSA level, Gleason score, and biochemical failure (relative risk 1.27) to be statistically significant variables., Conclusion: In addition to previously identified factors, the pretreatment PSA level and occurrence of biochemical failure after radiotherapy for prostate cancer are associated with an increased overall mortality risk. Both pretreatment PSA level and posttreatment biochemical failure are independent predictors of overall survival after radiotherapy for prostate cancer.

Purpose: To assess factors related to the risk of acute urinary retention and other morbidity indices in patients undergoing transperineal seed implantation of the prostate., Materials and Methods: One hundred and seventy-three consecutive patients treated with (125)Iodine transperineal interstitial permanent prostate brachytherapy (TIPPB) were evaluated. Various demographic, pathological, symptomatic, urodynamic and dosimetric values were assessed in relation to the incidence of acute urinary retention as well as the International Prostate Symptom Score (IPSS) dynamics. Patients were routinely placed on alpha-blockade postimplant. Dosimetry was based on CT scan one month postimplant., Results: Acute urinary retention developed in thirty-four patients (19.7%), at a median time of four days. Peak urinary flow rate was the only independent factor which varied significantly between those suffering retention and those not (median of 16 and 19.5 ml/s respectively, P=0.005). Median preimplant IPSS was 4.0, with a median peak of 16 at 3 months. Actuarial median time to return to baseline IPSS was at 15 months. The peak IPSS above preimplant levels was correlated significantly in multivariate analysis with the number of seeds implanted superior to the physician-nominated anatomical base level of the prostate (P<0.009), as well as lower preimplant IPSS values., Conclusions: In our series, preimplant urinary flow rate was the most important factor predictive of postimplant acute urinary retention. The patients' risk of having heightened IPSS change following implantation was correlated to a lower preimplant IPSS and an increased number of seeds implanted above the level of the prostatic base, possibly reflecting bladder base rather than urethral irritation in the development of acute urinary morbidity.

Purpose: To assess the efficacy of a variety of prognostic models in the definition of intermediate-risk prostate cancer and to compare them to our own empiric model., Methods and Materials: Two hundred fifty-six consecutive men with prostate adenocarcinoma treated with external beam radiotherapy alone were studied. Biochemical failure (defined as 3 consecutive PSA rises or the initiation of androgen deprivation therapy) was examined using univariate, multivariate, and recursive partitioning analyses. The risk classification model used in our department was then compared to a number of published models to assess the relative performance of each in discriminating risk groups., Results: At a median follow-up of 62.4 months, the 5-year Biochemical failure-free survival (bFFS) was 46.8% for the overall group. This relates to 5-year bFFS of 77.8%, 51.1%, and 33.8% based on our institutional criteria for low-, intermediate-, and high-risk features, respectively. All the models examined showed an outcome group with a comparatively similar poor outcome when applied to our data. Large variation was seen in the intermediate-risk groups, with 5-year bFFS ranging from 38.1% to 51.1%. Good risk categories had similar large variations. All published models showed inability to delineate three significantly different outcome groups. Recursive partitioning analysis derived categories based on combinations of PSA (with cutpoints at 42.4, 20, and 10.6 ng/mL) and Gleason score (with cutpoints at 2-6 and 7-10) only., Conclusions: Large variations in the relative performance of a number of prognostic models are shown when applied to our local data. The prognostic efficacy of PSA and biopsy Gleason score is reiterated, although other factors will need to be explored to further improve the performance of prognostic models, particularly in defining the intermediate-risk subset of prostate cancer.

The aim of this study was to assess current management of prostate cancer patients with elevated prostate-specific antigen (PSA) among Finnish urologists and oncologists. Four case scenarios were presented: postprostatectomy PSA relapse, postradiotherapy (RT) relapse with a slowly or rapidly rising PSA, elderly patients prior to treatment. Management preferences and the use of androgen deprivation (AD) in prostate cancer were surveyed. Eighty-two informative replies, 60 from 90 practicing urologists (67%) and 22 from 70 practicing oncologists (31%) were received. For postprostatectomy relapse, salvage RT or follow-up until significant rise of PSA were the favored recommendations. For post RT with slowly or rapidly rising PSA and treatment of non-radical cases an active approach with even small PSA rises and immediate androgen deprivation were favored. For intervention, the recommended PSA border values ranged from 0.5 to > 100 ng/mL. More research is needed focusing on criteria and timing of AD in the treatment of prostate cancer.