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PURPOSE: Accurate information regarding real-world outcomes after contemporary radiation therapy for localized prostate cancer is important for shared decision-making. Clinically relevant end points at 10 years among men treated within a national health care delivery system were examined. METHODS: National administrative, cancer registry, and electronic health record data were used for patients undergoing definitive radiation therapy with or without concurrent androgen deprivation therapy within the Veterans Health Administration from 2005 to 2015. National Death Index data were used through 2019 for overall and prostate cancer-specific survival and identified date of incident metastatic prostate cancer using a validated natural language processing algorithm. Metastasis-free, prostate cancer-specific, and overall survival using Kaplan-Meier methods were estimated. RESULTS: Among 41,735 men treated with definitive radiation therapy, the median age at diagnosis was 65 years and median follow-up was 8.7 years. Most had intermediate (42%) and high-risk (33%) disease, with 40% receiving androgen deprivation therapy as part of initial therapy. Unadjusted 10-year metastasis-free survival was 96%, 92%, and 80% for low-, intermediate-, and high-risk disease. Similarly, unadjusted 10-year prostate cancer-specific survival was 98%, 97%, and 90% for low-, intermediate-, and high-risk disease. The unadjusted overall survival was lower across increasing disease risk categories at 77%, 71%, and 62% for low-, intermediate-, and high-risk disease (p < .001). CONCLUSIONS: These data provide population-based 10-year benchmarks for clinically relevant end points, including metastasis-free survival, among patients with localized prostate cancer undergoing radiation therapy using contemporary techniques. The survival rates for high-risk disease in particular suggest that outcomes have recently improved.

Radiation therapy advanced practice has been implemented in several international jurisdictions; however, it is yet to be systematically integrated into Australian radiation oncology centres. This paper presents the outcomes of a doctoral research study to explore the factors that may be influencing the implementation of radiation therapy advanced practice in Australia. Using a constructivist grounded theory methodological approach to guide procedures, data collection occurred via 6 nationally facilitated online (video mediated) focus groups, and during interviews and observations at 5 purposively selected clinical case study locations. Data analysis led to the development of a grounded theory 'navigating uncertainty' to describe the process influencing the implementation of radiation therapy advanced practice in Australia. Navigating uncertainty is explained by three inter-related contextual processes of conceptualising radiation therapy advanced practice, integrating radiation therapy advanced practice, and becoming the radiation therapy advanced practitioner. The research suggests that the process of actively finding a way to accommodate uncertainty is necessary for advanced practice implementation objectives to be realised.

AIMS: Perineural invasion (PNI) by prostatic adenocarcinoma is debated as a prognostic parameter. This study investigates the prognostic predictive value of PNI in a series of patients with locally advanced prostate cancer treated with radiotherapy and androgen deprivation using 10 years outcome data from the TROG 03.04 RADAR trial. METHODS: Diagnostic prostate biopsies from 976 patients were reviewed and the presence of PNI noted. Patients were followed for 10 years according to the trial protocol or until death. The primary endpoint for the study was time to bone metastasis. Secondary endpoints included time to soft tissue metastasis, transition to castration resistance, prostate cancer-specific mortality and all-cause mortality. RESULTS: PNI was detected in 449 cases (46%), with 234 cases (24%) having PNI in more than one core. The presence of PNI was significantly associated with higher ISUP grade, clinical T staging category, National Comprehensive Cancer Network risk group, and percent positive biopsy cores. The cumulative probability of bone metastases according to PNI status was significant over the 10 years follow-up interval of the study (log-rank test P < 0.0001). PNI was associated with all endpoints on univariable analysis. After adjusting for baseline clinicopathological and treatment factors, bone metastasis was the only endpoint in which PNI retained its prognostic significance (hazard ratio 1.42, 95% confidence interval 1.05-1.92, P = 0.021). CONCLUSIONS: The association between PNI and the development of bone metastases supports the inclusion of this parameter as a component of the routine histology report. Further this association suggests that evaluation of PNI may assist in selecting those patients who should be monitored more closely during follow-up.

AIM: To report the trend in end-of-life health services (HS) utilization among cancer patients treated in a large Australian academic cancer center over a 12-year period. METHODS: This is a retrospective study of cancer patients treated at the Peter MacCallum Cancer Centre (PMCC), who had documented death between January 2002 and December 2013. Using administrative and billing database, we report on the utilization of different categories of HS within two weeks of death: diagnostic investigations (pathology and radiology), inpatient and outpatient services, and potentially futile interventions (PFI, which include radiotherapy, chemotherapy and surgery). RESULTS: Of the 27 926 "active" cancer patients in the study (i.e. those with medical contact at PMCC in the last year of life), 6368 (23%) had documented HS utilization within two weeks of death. 11% and 9% had pathology and radiology investigations respectively, 14% had outpatient clinic appointments, and 7% had hospital admissions. There were 2654 patients (10%) who had PFI within two weeks of death - 2198 (8%) had radiotherapy, 287 (1%) chemotherapy and 267 (1%) surgery. We observed peak HS and PFI utilization in 2004, which then dropped to its lowest in 2009/2010. CONCLUSION: Experience in an Australian cancer center suggests approximately one in four "active" cancer patients had HS utilization, and one in ten had PFI, within two weeks of death. The implementation of palliative care guidelines may reduce some of these potentially wasteful and futile interventions.

BACKGROUND: Prostate cancer management involves a balance between the risks of cancer death against those from other causes. To evaluate the performance of several comorbidity indices in predicting comorbid death in a prostate cancer radiotherapy cohort. METHODS: 2,131 men with localised prostate cancer treated with radical radiotherapy between 1999 and 2007 were studied. Tumour features, androgen deprivation usage, age, number of prescription medications (PMN) and Adult Comorbidity Evaluation-27 Index (ACE-27) were recorded. Death from prostate cancer (DPC) and death from other causes (DOC) were analysed as competing causes of death using a competing risks model, with discrimination assessed using the concordance index. RESULTS: ACE-27 scores correlated with patient's PMN (median PMN = 2). Tumour features were independent of ACE-27 scores. Estimated cumulative incidences of DOC and DPC at 10 years were 16.4% and 7.7% respectively. In the low/intermediate risk group (n = 1026) there was a 3.4-fold predominance of DOC inside 10 years (cumulative incidence: 15.8% DOC vs 3.4% DPC). High-risk men had approximately equal rates of DPC and DOC at 10 years. Multivariable analysis showed age, ACE-27 score ≥ 1 and PMN to have significant associations with DOC (P < 0.002 for all). A multivariable model incorporating all 3 variables resulted in C-Index = 0.646. CONCLUSION: Age, ACE-27 score and PMN act as independent prognostic factors for DOC in prostate cancer patients and can improve patient's life expectancy prediction.

BACKGROUND: It remains unclear whether eradication of oligometastases by stereotactic body radiation therapy or other means will result in cure or prolongation of survival in some cases, or merely provide palliation. We address this issue with prospectively collected progression and treatment data from the TROG 03.04 RADAR randomised controlled trial for men with locally advanced prostate cancer (PC). METHODS: Three Fine and Gray competing risk survival models with time-dependent covariates were used to determine whether metastatic progression status at first diagnosis of bony metastases, i.e. number of bony sites involved and presence of prior or simultaneous other sites of progression, impacts on prostate cancer-specific mortality (PCSM) when adjusted for baseline prognostic factors and allocated primary treatment. RESULTS: Between 2003 and 2014, 176 of the 1071 subjects developed bone metastases, 152 developed other sites of progression and 91 died of PC. All subjects received secondary treatment using androgen suppression but none received extirpative treatments. The three models found evidence: 1 - of a clear prognostic gradient according to number of bony metastatic sites; 2 - that other sites of progression contributed to PCSM to a lesser extent than bone progression; and 3 - that further bony metastatic progression in men with up to 3 bony metastases had a major impact on PCSM. CONCLUSION: Randomised trials are essential to determine the value of extirpative treatment for oligometastatic bony metastases due to PC.

BACKGROUND: Radiotherapy for localised prostate cancer has many known and distressing side effects. The efficacy of group interventions for reducing psychological morbidity is lacking. This study investigated the relative benefits of a group nurse-led intervention on psychological morbidity, unmet needs, treatment-related concerns and prostate cancer-specific quality of life in men receiving curative intent radiotherapy for prostate cancer. METHODS: This phase III, two-arm cluster randomised controlled trial included 331 men (consent rate: 72 %; attrition: 5 %) randomised to the intervention (n = 166) or usual care (n = 165). The intervention comprised four group and one individual consultation all delivered by specialist uro-oncology nurses. Primary outcomes were anxious and depressive symptoms as assessed by the Hospital Anxiety and Depression Scale. Unmet needs were assessed with the Supportive Care Needs Survey-SF34 Revised, treatment-related concerns with the Cancer Treatment Scale and quality of life with the Expanded Prostate Cancer Index -26. Assessments occurred before, at the end of and 6 months post-radiotherapy. Primary outcome analysis was by intention-to-treat and performed by fitting a linear mixed model to each outcome separately using all observed data. RESULTS: Mixed models analysis indicated that group consultations had a significant beneficial effect on one of two primary endpoints, depressive symptoms (p = 0.009), and one of twelve secondary endpoints, procedural concerns related to cancer treatment (p = 0.049). Group consultations did not have a significant beneficial effect on generalised anxiety, unmet needs and prostate cancer-specific quality of life. CONCLUSIONS: Compared with individual consultations offered as part of usual care, the intervention provides a means of delivering patient education and is associated with modest reductions in depressive symptoms and procedural concerns. Future work should seek to confirm the clinical feasibil

Introduction Prostate cancer is common and may be treated immediately or managed conservatively by observation. We sought to determine how reliable multiparametric MRI is in the detection of intraprostatic prostate cancer and what role it has in risk stratification. Methods The histology from 38 whole mount prostate specimens was compared with preoperative multiparametric 3T MRI studies with an endorectal receiver coil in place. T1-weighted, T2-weighted, diffusion (b values 50 400 800), perfusion (Ve, Kep, Ktrans, area under the curve) and proton spectroscopic sequences were used. Results For cancers greater than 0.5 cc, the detection rate for combined T2-weighted imaging and diffusion-weighted imaging (DWI) was 85%. For cancers 0.1 cc-0.5 cc, the sensitivity was 52%.Per patient, false positive rate was 50% for combined T2-weighted imaging and DWI. Perfusion imaging had a sensitivity of 70% for tumours greater than 0.5 cc but had a per patient false positive rate of 80% influenced by benign prostatic hypertrophy. In only 15 patients could a satisfactory spectroscopy study be obtained. Weak correlation was found between the Gleason score and tumour size (r = 0.51), apparent diffusion coefficient (ADC) (r = -0.30) and (choline + creatine)/citrate ratio (r = 0.41). Conclusion T2-weighted imaging and DWI in combination were the best strategy for detecting prostate cancer and had a sensitivity of 85% for detecting lesions greater than 0.5 cc. At 3T, an ADC threshold of between 1100-1200.10-6 mm 2/s was optimal for diagnosing prostate cancer. There are significant limitations in the use of perfusion and spectroscopy to detect prostate cancer. Magnetic resonance imaging-targeted or guided biopsy post-MRI imaging is likely to be needed in some patients to assist risk stratification. © 2014 The Royal Australian and New Zealand College of Radiologists.

Introduction: National and international guidelines have recommended the use of adjuvant post prostatectomy radiotherapy (PPRT) for high risk patients but concerns about potential toxicity have limited its implementation. The preliminary results of late toxicity in the adjuvant therapy arm from the RAVES trial are reported so clinicians can appropriately inform patients of the potential toxicity of adjuvant PPRT in a contemporary Australian and New Zealand series. Patients and Methods: The phase 3 multi-site trial is sponsored by the Trans Tasman Radiation Oncology Group, in collaboration with the Urological Society of Australia and New Zealand and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. As of November 2013, 259 patients have been randomised towards the total sample size of 470. We evaluated 101 patients randomised to the adjuvant radiation therapy arm of the RAVES trial that had a minimum follow-up of 12 months. All patients received 64Gy in 32 fractions within 4 months of surgery. Treatment plans were reviewed prior to commencement of RT in accordance with trial quality assurance procedures. The National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) were used to prospectively assess acute and late GU and GI toxicity and erectile dysfunction. The EORTC global (QLQ-C30) and EORTC QLQ-PR25 were used to assess quality of life (QoL). Result(s): 101 patients were available for analysis with 101, 82 and 51 patients completing 1,2 and 3 year follow up respectively. All patients completed radiotherapy as per protocol. 33% had >= grade 2 genito-urinary (GU) dysfunction and 0% had >= grade 2 gastro-intestinal (GI) dysfunction at baseline. The incidence of >= grade 2 late GU dysfunction at 24 and 36 months was 22% and 25%. The incidence of >= grade 2 late GI dysfunction at 24 and 36 months was 6% and 2%. At baseline 3% of patients felt that their daily activities had been limited quite a bit or very muc

Purpose: To examine the accuracy of multiparametric 3T MRI in detecting the presence and distribution of prostate cancer within the gland. Methods and materials: 25 patients with biopsy-proven prostate cancer, average age 61, who had MRI as part of pre-prostatectomy work-up. A Siemens 3T Trio system performed triplanar T2, transverse T1, and diffusion-weighted sequences (b values 50, 40, 800), as well as a perfusionstudy of the whole prostate (5.4-s increments, for approximately 9 min; post-processed for maps of AUC, Ktrans, Ve, Kep) and 3D proton spectroscopy. 2 other patients declined the endorectal coil. The excised prostate gland was fixed and sectioned, the apical and basal portions transected and sectioned para-sagitally, the remainder sectioned axially. Prostate cancer was scored according to the Gleason scale, and the presence of prostate cancer marked on the whole mount slides to allow correlation with MR images. Result(s): Within the 25 prostatic specimens, 29 cancers measured 0.5 cc or more, there were 21 cancers between 0.5 cc and 0.1 cc, and 0.28 cancers were less than 0.1 cc, considered below the detection threshold. Most tumours were Gleason score (3 + 4) or (4 + 3). Tumour detection Lesion >0.5 cc 0.5 cc > Lesion > 0.1 cc False positive DWI (ADC < 1100) 26/29 sites 6/21 15 sites in 9 patients T2 23/29 4/21 7 sites in 7 patients In the perfusion study, the AUC (area under curve) best discriminated tumour (mean 7.3 +/- 5.0, arbitrary units) from a contralateral control site (4.7 +/- 3.7), but group overlap existed, influenced by BPH. Spectroscopy was compromised by lack of sensitivity in deeper portions of the prostate, and artefacts; it did not prove reliable in the detection of prostate cancer in this group. Conclusion(s): The combination of T2 and DWI imaging (ADC <1100) was the most reliable in the detection of prostate tumours greater than 0.5 cc. Tumour delineation was best performed with the ADC map, but was occasionally incomplete. Further hist

BACKGROUND: To analyze interfraction motion of seminal vesicles (SV), and its motion relative to rectal and bladder filling. METHODS AND MATERIALS: SV and prostate were contoured on 771 daily computed tomography "on rails" scans from 24 prostate cancer patients undergoing radiotherapy. Random and systematic errors for SV centroid displacement were measured relative to the prostate centroid. Margins required for complete geometric coverage of SV were determined using isotropic expansion of reference contours. SV motion relative to rectum and bladder was determined. RESULTS: Systematic error for the SV was 1.9 mm left-right (LR), 2.9 mm anterior-posterior (AP) and 3.6 mm superior-inferior (SI). Random error was 1.4 mm (LR), 2.7 mm (AP) and 2.1 mm (SI). 10 mm margins covered the entire left SV and right SV on at least 90% of fractions in 50% and 33% of patients and 15 mm margins covered 88% and 79% respectively. SV AP movement correlated with movement of the most posterior point of the bladder (mean R2 = 0.46, SD = 0.24) and rectal area (mean R2 = 0.38, SD = 0.21). CONCLUSIONS: Considerable interfraction displacement of SV was observed in this cohort of patients. Bladder and rectal parameters correlated with SV movement.

BACKGROUND: Androgen deprivation therapy leads to a number of adverse effects including deterioration of the musculoskeletal system and increased risk factors for cardiovascular and metabolic complications. The purpose of this study is to determine the effects, efficacy, retention and compliance of a physical exercise intervention in a large established cohort of prostate cancer patients from the Randomised Androgen Deprivation and Radiotherapy (RADAR) study. Specifically, we aim to compare short- and long-term effects of a prostate cancer-specific supervised exercise program to a standard public health physical activity strategy utilizing printed resources on cardiovascular and metabolic risk factors. Our primary outcomes are cardiorespiratory capacity, abdominal obesity, and lipid and glycemic control, while secondary outcomes include self-reported physical activity, quality of life and psychological distress. METHODS/DESIGN: Multi-site randomized controlled trial of 370 men from the RADAR study cohort undergoing treatment or previously treated for prostate cancer involving androgen deprivation therapy in the cities of Perth and Newcastle (Australia), and Wellington (New Zealand). Participants will be randomized to (1) supervised resistance/aerobic exercise or (2) printed material comprising general physical activity recommendations. Participants will then undergo progressive training for 6 months. Measurements for primary and secondary endpoints will take place at baseline, 6 months (end of intervention), and at 6 months follow-up. DISCUSSION: This study uses a large existent cohort of patients and will generate valuable information as to the continuing effects of exercise specifically targeting cardiovascular function and disease risk, insulin metabolism, abdominal obesity, physical function, quality of life and psychological distress. We expect dissemination of the knowledge gained from this project to reduce risk factors for the development of co-morbid diseas

OBJECTIVE: Prostate cancer (PCA) is the most common malignancy and a major cause of death in men but, importantly, a substantial proportion will live for several years following diagnosis. However, they face the prospect of experiencing symptoms, side-effects of treatment and diminished quality of life. The patient's psychological adjustment is particularly complex, given the potential trajectory of the disease, from the point of diagnosis, with its immediate impact, to the phase of palliative care, with its attendant issue of facing mortality. Since a comprehensive review of the literature on psychological adjustment of men with PCA has not yet been done, we have documented relevant research, integrated findings and drawn conclusions, where possible, in order to map out clinical and research implications. METHOD: We searched 5 databases for the period 1994 - July 2006, during which most of the work in the field has been done. RESULTS: We found few studies of substance among the 60 we examined to draw conclusions about psychological adjustment to prostate cancer and its treatment. This is in marked contrast to the picture in breast cancer. While some patterns have emerged, many gaps remain to be filled. DISCUSSION: Aspects of methodology need attention, particularly longitudinal, prospective designs, incorporation of control groups and the use of valid and reliable measures. There is scope for qualitative studies as a complement to quantitative research.