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.

A contemporary, nationwide analysis of surgery and radiotherapy treatment for prostate cancer.

OBJECTIVE: To characterize national clinical practice trends in the treatment of prostate cancer (PCa) in Australia. PATIENTS AND METHODS: Population-level data were extracted from existing Medicare Benefits Schedule data for radical prostatectomy (RP) and brachytherapy (2002-2016), as well as external beam radiotherapy (EBRT; 2012-2016). Treatment rates were calculated relative to whole and PCa populations among privately treated patients. Overall age-related and geographical trends were analysed. RESULTS: The use of RP and low-dose-rate (LDR) brachytherapy increased between 2002 and 2009, but subsequently decreased to 124 and 6.9 per 100 000 men, respectively, in 2016. More dramatic decreases were observed for men aged <65 years. From 2012, rates of RP (15% drop) and LDR brachytherapy (58% drop) decreased, while the use of EBRT remained steady, falling by 5% to 42 per 100 000 men in 2016. Overall treatment increased in the age group 75-84 years, with the rate of RP increasing by 108%. CONCLUSION: National claims data indicate there has been a reduction in PCa treatment since 2009, which is mostly attributable to a reduction in the treatment of younger patients and reduced use of brachytherapy. RP is most commonly used and its use is rising in men aged >65 years.

Attenuation of Metabolic Syndrome by EPA/DHA Ethyl Esters in Testosterone-Deficient Obese Rats.

Inducing testosterone deficiency, as the standard treatment of prostate cancer, may cause metabolic disorders including insulin resistance, dyslipidemia, central obesity, cardiovascular diseases, and type 2 diabetes. This study measured responses to testosterone deficiency in high-carbohydrate, high-fat (H) diet-fed rats. We then tested whether eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) ethyl esters (Omacor) reversed these metabolic changes. Male Wistar rats (8⁻9 weeks old) were divided into eight groups with four groups fed corn starch and four groups fed H diet. For each diet, one group received diet only; one group was orchidectomized; one group was given leuprolide (gonadotrophin-releasing hormone agonist, 2 mg/kg every 4th week); and the last group was treated with leuprolide and their diet was supplemented with 3% Omacor for the last eight weeks. The protocol was for 16 weeks. Leuprolide worsened metabolic syndrome symptoms and cardiovascular function, and orchidectomy produced greater responses. In H fed leuprolide-treated rats, Omacor decreased systolic blood pressure and left ventricular diastolic stiffness, reduced infiltration of inflammatory cells and collagen deposition in the heart, and reduced lipid accumulation and inflammatory cell infiltration without improving liver damage. These results suggest that Omacor has potential to attenuate metabolic complications in prostate cancer patients with induced testosterone deprivation.

PROstate Multicentre External beam radioTHErapy Using a Stereotactic boost: the PROMETHEUS study protocol.

BACKGROUND: High Dose Rate Brachytherapy (HDRB) boost is a well-established treatment for prostate cancer (PC). We describe the PROstate Multicentre External beam radioTHErapy Using Stereotactic boost (PROMETHEUS) study. Non-surgical stereotactic techniques are used to deliver similar doses to HDRB boost regimens with a dose escalation sub-study. METHODS: Eligible patients have intermediate or high risk PC. PROMETHEUS explores the safety, efficacy and feasibility of multiple Australian centres cooperating in the delivery of Prostate Stereotactic Body Radiotherapy (SBRT) technology. A SBRT boost component Target Dose (TD) of 19Gy in two fractions is to be delivered, followed by a subsequent EBRT component of 46Gy in 23 fractions. Once accrual triggers have been met, SBRT doses can be escalated in 1 Gy increments to a maximum of 22Gy in two fractions. Patient safety will also be measured with the rate of both acute and late moderate to severe Gastro-Intestinal (GI) and Genito-Urinary (GU) Common Terminology Criteria for Adverse Events (CTCAE) toxicities as well as patient reported quality of life. Efficacy will be assessed via biochemical control after 3 years. DISCUSSION: PROMETHEUS aims to generate evidence for a non-surgical possible future alternative to HDRB boost regimens, and introduce advanced radiotherapy techniques across multiple Australian cancer centres. TRIAL REGISTRATION: The study was retrospectively registered on the ANZCTR (Australian New Zealand Clinical Trials Registry) with trial ID: ACTRN12615000223538 .

Complementary and alternative medicine use in radiotherapy: what are patients using?

OBJECTIVES: Complementary and alternative medicine (CAM) use by patients could interact in unpredictable ways with conventional therapies. This trial was designed to study the prevalence, types, and clinical implications of CAM use in patients with cancer who are receiving radiotherapy. DESIGN: A validated questionnaire was given to consenting outpatients in this ethics-approved study. Questions specified types of CAM used, clinician knowledge, reason for use, perceived effectiveness, safety, and cost. RESULTS: Of the 101 assessable questionnaires, 38 patients (38%) of the total patient group used CAM, with vitamins (53%), antioxidants (29%), spiritual/meditation practices (29%), and herbs (18%) being the most commonly used. The intention of CAM use was to improve quality of life in 69% of patients and for either hope of cure or to assist other forms of treatment in 26%. The majority of patients (58%) were using CAM prior to their diagnosis of cancer, with 40% starting at diagnosis or during conventional treatment. Patients spent up to $300/month on CAM use. Patients using CAM were significantly more likely to also receive chemotherapy versus non-CAM users (45% versus 24%, p=0.045). Significantly fewer CAM users expected cure from conventional therapy, compared to non-CAM users (50% versus 75%, p=0.016). More CAM users expected conventional therapy to prolong life (58% versus 32%, p<0.001). Only 40% discussed CAM use with their oncologists. CONCLUSIONS: CAM is commonly used by patients with cancer. CAMs, particularly antioxidants, are being taken which could negate the underlying free-radical tumorcidal effects of radiotherapy. Oncologists need to have greater awareness of this use and of its potential adverse consequences.