Evaluation of Hypofractionated Radiation Therapy Use and Patient-Reported Outcomes in Men With Nonmetastatic Prostate Cancer in Australia and New Zealand.

Importance: Randomized clinical trials in prostate cancer have reported noninferior outcomes for hypofractionated radiation therapy (HRT) compared with conventional RT (CRT); however, uptake of HRT across jurisdictions is variable. Objective: To evaluate the use of HRT vs CRT in men with nonmetastatic prostate cancer and compare patient-reported outcomes (PROs) at a population level. Design, Setting, and Participants: Registry-based cohort study from the Australian and New Zealand Prostate Cancer Outcomes Registry (PCOR-ANZ). Participants were men with nonmetastatic prostate cancer treated with primary RT (excluding brachytherapy) from January 2016 to December 2019. Data were analyzed in March 2021. Exposures: HRT defined as 2.5 to 3.3 Gy and CRT defined as 1.7 to 2.3 Gy per fraction. Main Outcomes and Measures: Temporal trends and institutional, clinicopathological, and sociodemographic factors associated with use of HRT were analyzed. PROs were assessed 12 months following RT using the Expanded Prostate Cancer Index Composite (EPIC)-26 Short Form questionnaire. Differences in PROs were analyzed by adjusting for age and National Comprehensive Cancer Network risk category. Results: Of 8305 men identified as receiving primary RT, 6368 met the inclusion criteria for CRT (n = 4482) and HRT (n = 1886). The median age was 73.1 years (IQR, 68.2-77.3 years), 2.6% (168) had low risk, 45.7% (2911) had intermediate risk, 44.5% (2836) had high-/very high-risk, and 7.1% (453) had regional nodal disease. Use of HRT increased from 2.1% (9 of 435) in the first half of 2016 to 52.7% (539 of 1023) in the second half of 2019, with lower uptake in the high-/very high-risk (1.9% [4 of 215] to 42.4% [181 of 427]) compared with the intermediate-risk group (2.2% [4 of 185] to 67.6% [325 of 481]) (odds ratio, 0.26; 95% CI, 0.15-0.45). Substantial variability in the use of HRT for intermediate-risk disease remained at the institutional level (median 53.3%; range, 0%-100%) and clinician level (median 57.9%; range, 0%-100%) in the last 2 years of the study period. There were no clinically significant differences across EPIC-26 urinary and bowel functional domains or bother scores. Conclusions and Relevance: In this cohort study, use of HRT for prostate cancer increased substantially from 2016. This population-level data demonstrated clinically equivalent PROs and supports the continued implementation of HRT into routine practice. The wide variation in practice observed at the jurisdictional, institutional, and clinician level provides stakeholders with information that may be useful in targeting implementation strategies and benchmarking services.

Musculoskeletal Responses to Exercise Plus Nutrition in Men with Prostate Cancer on Androgen Deprivation: A 12-Month RCT.

PURPOSE: Androgen deprivation therapy (ADT) for prostate cancer has multiple adverse effects on musculoskeletal health. This 12-month randomized controlled trial aimed to assess the effects of multicomponent exercise training combined with whey protein, calcium and vitamin D supplementation on bone mineral density (BMD), structure and strength, body composition, muscle strength, and physical function in ADT-treated men. METHODS: Seventy ADT-treated men were randomized to exercise plus supplementation (Ex + Suppl; n = 34) or usual care (control; n = 36). Ex + Suppl involved thrice weekly progressive resistance training plus weight-bearing impact exercise with daily multinutrient supplementation. Primary outcomes were DXA hip and spine areal BMD. Secondary outcomes included the following: tibia and radius pQCT volumetric BMD, bone structure and strength, DXA body composition, pQCT muscle and fat cross-sectional area and muscle density, and muscle strength and physical function. RESULTS: Sixty men (86%) completed the study. Mean exercise and supplement adherence were 56% and 77%, respectively. There were no effects of the intervention on bone or body composition outcomes. Ex + Suppl improved leg muscle strength (net difference, (95% confidence interval, or CI), 14.5% (-0.2 to 29.2); P = 0.007) and dynamic mobility (four-square-step test time, -9.3% (-17.3 to -1.3), P = 0.014) relative to controls. Per-protocol analysis of adherent participants (≥66% exercise, ≥80% supplement) showed Ex + Suppl preserved femoral neck aBMD (1.9% (0.1 to 3.8), P = 0.026) and improved total body lean mass (1.0 kg (-0.23 to 2.22), P = 0.044) relative to controls. CONCLUSIONS: Exercise training combined with multinutrient supplementation had a limited effect on ameliorating the adverse musculoskeletal consequences of ADT, likely related to the modest intervention adherence.

Improved survival for patients with prostate cancer receiving high-dose-rate brachytherapy boost to EBRT compared with EBRT alone.

PURPOSE: High-dose-rate (HDR) brachytherapy boost is a treatment of intermediate- to high-risk prostate cancer, but long-term clinical outcome data are sparse. We report long-term survival and toxicity data in a cohort of patients treated in a single institution. METHODS: Between 1998 and 2004, 654 patients with localized prostate cancer received either 3-dimensional conformal radiotherapy (median 46 Gy) with an HDR (median 18 Gy in three fractions) boost ("3-D conformal radiotherapy [3DCRT] + HDR"; 215 patients) or 3DCRT alone ("3DCRT"; median 70 Gy; 439 patients) with curative intent. Men with National Comprehensive Cancer Network intermediate risk were offered neoadjuvant androgen deprivation and with high risk were also offered adjuvant androgen deprivation. Data collection included patient-reported outcome measures. RESULTS: The 3DCRT + HDR group was older (72.3 vs. 68.9 yrs), had higher presenting PSAs (iPSA) (15.66 and 12.57 ng/mL, respectively), higher proportion of Gleason scores >7 (15.3% vs. 12.4%), and higher proportions of extracapsular disease (29.3% vs. 25.5%). 3DCRT + HDR men had lower proportions of low-risk patients (3.3% vs. 19.4%) and higher proportions of high-risk patients (50.7% vs. 37.4%) than the 3DCRT group. The 5-, 10-, and 15-year overall survival was superior at 92%, 81%, and 67%, respectively, for the 3DCRT + HDR group, compared with 88%, 71%, and 53%, respectively, in the 3DCRT group (p < 0.001). The 5-, 10-, and 15-year cause specific survival also favored the HDR boost group with survival of 96%, 93%, and 87% (3DCRT + HDR) and 95% 88% and 79% (3DCRT), respectively (p < 0.037). CONCLUSIONS: HDR brachytherapy boost in conjunction with 3DCRT offered superior overall survival and cause-specific survival in our patient population.

Interpolation to define clinical tumor stage in prostate cancer using clinical description of digital rectal examination.

AIM: This study aims to assess characteristics of patients with prostate cancer for whom clinical T stage category (cT) was not documented in the medical record and assess whether specialists had concordant conclusions regarding cT based on digital rectal examination (DRE) notes. METHODS: Data from the Prostate Cancer Outcome Registry - Victoria (PCOR-Vic) were interrogated. Four specialists independently assigned cT to DRE notes. Words, or part thereof, associated with agreement between clinicians were identified. RESULTS: Of the 10 587 men, cT was documented in 8758 (82.7%) cases. Multivariate analysis indicated that poor cT documentation was associated with older patient age (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.66-0.99 if 75.1-85 years; OR 0.50, 95%CI 0.36-0.72 if >85 years); diagnosis via transperineal compared to transrectal ultrasound-guided biopsy (TRUS) (OR 0.68, 95%CI 0.51-0.91); diagnosed in a private hospital (OR 0.85, 95%CI 0.75-0.96); and a diagnostic Gleason score of >8 compared to ≤6 (OR 0.59, 95%CI = 0.48-0.73). cT was more likely documented in men diagnosed via transurethral resection of prostate (OR 2.06, 95%CI 1.64-2.58) compared to TRUS and/or if receiving treatment in a radiotherapy center (OR 3.44, 95%CI 2.80-4.23 for external beam radiotherapy; OR 3.57 95%CI 2.44-5.23 for brachytherapy and OR 1.34, 95%CI 1.06-1.69 for combination surgery and radiotherapy) compared to those undergoing radical prostatectomy. Agreement in cT assignment ranged from kappa of 0.158 to 0.582. Stem word components in DRE notes associated with poorest level of agreement were "abnorm," "hard," "nodul" and those with highest level of agreement were terms "benign" and "smooth." CONCLUSIONS: Mode of diagnosis/subsequent treatment, and cancer characteristics were associated with cT documentation. Third party interpretation of clinical notes is problematic.

Efficacy of a multi-component exercise programme and nutritional supplementation on musculoskeletal health in men treated with androgen deprivation therapy for prostate cancer (IMPACT): study protocol of a randomised controlled trial.

BACKGROUND: Prostate cancer is the most commonly diagnosed cancer in men in developed countries. Androgen deprivation therapy (ADT) is a systemic treatment shown to increase survival in selected patients with prostate cancer. The use of ADT continues to increase for all stages and grades of prostate cancer despite known treatment-induced adverse effects. The primary aim of this study is to examine the efficacy of a targeted, multi-component resistance and impact-loading exercise programme together with a daily protein-, calcium- and vitamin D-enriched supplement on bone health in men treated with ADT for prostate cancer. Secondary aims are to determine the effects of this intervention on measures of total body and regional body composition, cardiometabolic risk, inflammatory markers, health-related quality of life and cognitive function. METHODS: This study is a two-arm randomised controlled trial. Men currently treated with ADT for prostate cancer will be randomised to either a 52-week, community-based, exercise training and nutritional supplementation intervention (n = 51) or usual care control (n = 51). Participants will be assessed at baseline, 26 weeks and 52 weeks for all measures. The primary outcome measures are proximal femur and lumbar spine areal bone mineral density (BMD). Secondary outcomes comprise: changes in tibial and radial bone structure and strength, total body and regional body composition, muscle strength and function, as well as cardiometabolic health, catabolic/inflammatory and anabolic/anti-inflammatory cytokines, health-related quality of life and cognitive function. DISCUSSION: This study investigates whether a multi-component intervention incorporating a targeted bone and muscle-loading programme in combination with a protein-, calcium- and vitamin D-enriched supplement can ameliorate multiple adverse effects of ADT when compared to usual care. The results will contribute to the development of exercise training and nutrition guidelines for optimising overall health in men treated with ADT for prostate cancer. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry (ANZCTR), ID: ACTRN12614000317695 . Registered on 25 march 2014.

Comparison of oncological and health-related quality of life outcomes between open and robot-assisted radical prostatectomy for localised prostate cancer - findings from the population-based Victorian Prostate Cancer Registry.

OBJECTIVE: To compare the short-term oncological and health-related quality of life (HRQOL) outcomes between open (ORP) and robot-assisted (RARP) radical prostatectomy in the population-based Victorian Prostate Cancer Registry. PATIENTS AND METHODS: This is a prospective cohort of patients with prostate cancer who had RP (1117 ORP and 885 RARP) between January 2009 and June 2012. The oncological outcomes of interest were: positive surgical margin (PSM) and biochemical recurrence (BCR), defined as postoperative PSA level of >0.2 ng/mL. The HRQOL outcomes were: sexual and urinary bother, assessed using the Expanded Prostate Cancer Index Composite at 1- and 2-years after diagnosis. For univariate comparison of continuous variables the Student's t-test or Mann-Whitney U-test were used, and the Pearson's chi-squared test was used for categorical variables. Bonferroni correction was applied to account for multiple testing, with a threshold for significance of P < 0.003 for univariate analyses. The inverse-probability-treatment-weighting (IPTW) approach was used to adjust for differences in baseline characteristics between ORP and RARP patients [including age, National Comprehensive Cancer Network (NCCN) risk categories, hospitals, and year of RP] in all multivariate analyses. Logistic regressions were used to analyse for PSM, Cox regressions for BCR, and ordinal logistic regressions for HRQOL outcomes. All multivariate analyses also adjusted for surgeons' average annual caseload, and employed the robust standard errors for clustering by surgeon. RESULTS: ORP and RARP patients were followed for a median of 19 and 17 months, respectively. The proportion of patients with NCCN low-risk prostate cancer was significantly higher among RARP patients (21% vs 26%; P = 0.002). Most RPs was done in private hospitals (77% ORP, and 85% RARP, P < 0.001). A higher proportion of RARP patients were operated by surgeons with higher annual caseloads (65% RARP and 53% ORP operated by surgeons with >20 case/year; P < 0.001). In the IPTW-adjusted multivariate analyses, RARP patients had a lower risk of PSM (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.38-0.81), and BCR (hazard ratio [HR] 0.73, 95% CI 0.55-0.99). In the sensitivity analyses (excluding public hospital patients), the lower PSM risk with RARP remained (OR 0.63, 95% CI 0.38-0.81), but the lower BCR risk with RARP was no longer statistically significant (HR 0.79, 95% CI 0.57-1.12). At 1-year follow-up, 61% of ORP and 59% of RARP patients reported 'moderate-big' sexual bother (P = 0.2), while 14% of ORP and 11% of RARP patients reported 'moderate-big' urinary bother (P = 0.08). The sexual and urinary bothers at 2 years were similar between ORP and RARP. In multivariate analyses, there were no statistically significant differences in the HRQOL outcomes between ORP and RARP. CONCLUSIONS: We report on a large population-based comparative study of ORP and RARP with better short-term oncological outcomes favouring RARP, but no significant differences in HRQOL outcomes. The results have to be interpreted taking into account significant surgeon heterogeneity in a population-based study.

Patterns of care for men diagnosed with prostate cancer in Victoria from 2008 to 2011.

OBJECTIVE: To describe patterns of care for men diagnosed with prostate cancer in Victoria, Australia, between 2008 and 2011. DESIGN, SETTING AND PATIENTS: Men who were diagnosed with prostate cancer at 11 public and six private hospitals in Victoria from August 2008 to February 2011, and for whom prostate cancer notifications were received by the Prostate Cancer Registry. MAIN OUTCOME MEASURES: Characteristics of men diagnosed with prostate cancer; details of treatment provided within 12 months of diagnosis, according to National Comprehensive Cancer Network risk categories; and characteristics of men who did not receive active treatment within 12 months of diagnosis. RESULTS: Treatment details were collected for 98.1% of men who were assessed as eligible to participate in the study (2724/2776) and were confirmed by telephone 12 months after diagnosis for 74.4% of them (2027/2724). Most patients (2531/2724 [92.9%]) were diagnosed with clinically localised disease, of whom 1201 (47.5%) were at intermediate risk of disease progression. Within 12 months of diagnosis, 299 of the 736 patients (40.6%) who had been diagnosed as having disease that was at low risk of progression had received no active treatment, and 72 of 594 patients (12.1%) who had been diagnosed as having disease that was at high risk of progression had received no active treatment. Of those diagnosed as having intermediate risk of disease progression, 54.5% (655/1201) had undergone radical prostatectomy. Those who received no active treatment were more likely than those who received active treatment to be older (odds ratio [95% CI], 2.96 [2.01-4.38], 10.94 [6.96-17.21] and 32.76 [15.84-67.89], respectively, for age 65-74 2013s, 75-84 2013s and ≥ 85 2013s, compared with < 55 2013s), to have less advanced disease (odds ratio [95% CI], 0.20 [0.16-0.26], 0.09 [0.06-0.12] and 0.05 [0.02-0.90], respectively, for intermediate, high and very high-risk [locally advanced] or metastatic disease, compared with low-risk disease) and to have had their prostate cancer notified by a private hospital (odds ratio [95% CI], 1.35 [1.10-1.66], compared with public hospital). CONCLUSION: Our data reveal a considerable "stage migration" towards earlier diagnosis of prostate cancer in Victoria and a large increase in the use of radical prostatectomy among men with clinically localised disease.

The Prostate Cancer Registry: monitoring patterns and quality of care for men diagnosed with prostate cancer.

OBJECTIVE: To establish a pilot population-based clinical registry with the aim of monitoring the quality of care provided to men diagnosed with prostate cancer. PATIENTS AND METHODS: All men aged >18 years from the contributing hospitals in Victoria, Australia, who have a diagnosis of prostate cancer confirmed by histopathology report notified to the Victorian Cancer Registry are eligible for inclusion in the Prostate Cancer Registry (PCR). A literature review was undertaken aiming to identify existing quality indicators and source evidence-based guidelines from both Australia and internationally. RESULTS: A Steering Committee was established to determine the minimum dataset, select quality indicators to be reported back to clinicians, identify the most effective recruitment strategy, and provide a governance structure for data requests; collection, analysis and reporting of data; and managing outliers. A minimum dataset comprising 72 data items is collected by the PCR, enabling ten quality indicators to be collected and reported. Outcome measures are risk adjusted according to the established National Comprehensive Cancer Network and Cancer of the Prostate Risk Assessment Score (surgery only) risk stratification model. Recruitment to the PCR occurs concurrently with mandatory notification to the state-based Cancer Registry. The PCR adopts an opt-out consent process to maximize recruitment. The data collection approach is standardized, using a hybrid of data linkage and manual collection, and data collection forms are electronically scanned into the PCR. A data access policy and escalation policy for mortality outliers has been developed. CONCLUSIONS: The PCR provides potential for high-quality population-based data to be collected and managed within a clinician-led governance framework. This approach satisfies the requirement for health services to establish quality assessment, at the same time as providing clinically credible data to clinicians to drive practice improvement.