Protocol of a randomised, controlled trial comparing immediate curative therapy with conservative treatment in men aged ≥75 years with non-metastatic high-risk prostate cancer (SPCG 19/GRand-P).

BACKGROUND: Older men (aged ≥75 years) with high risk, non-metastatic prostate cancer (PCa) are increasingly treated with curative therapy (surgery or radiotherapy). However, it is unclear if curative therapy prolongs life and improves health-related quality of life (HRQoL) in this age group compared to conservative therapy, which has evolved considerably during the last decade. STUDY DESIGN: The Scandinavian Prostate Cancer Group (SPCG) 19/Norwegian Get-Randomized Research Group-Prostate (GRand-P) is a randomised, two-armed, controlled, multicentre, phase III trial carried out at study centres in Norway, Denmark, Finland, and Sweden. ENDPOINTS: The primary endpoints are overall survival and HRQoL (burden of disease scale, European Organisation for the Research and Treatment of Cancer [EORTC] Elderly Cancer patients). Secondary endpoints are PCa-specific survival, metastasis-free survival, role-functioning scale (EORTC quality of life questionnaire 30-item core), urinary irritative/obstructive scale (26-item Expanded Prostate Cancer Index Composite [EPIC-26]), bowel scale (EPIC-26), intervention-free survival, PCa morbidity, use of secondary and tertiary systemic therapies, mean quality-adjusted life-years (QALYs), and mean total healthcare costs. PATIENTS AND METHODS: A total of 980 men (aged ≥75 years) with non-metastatic, high-risk PCa will initially be screened with Geriatric 8 (G8) health status screening tool and Mini-COG© brief cognitive test. Participants identified by G8 as 'fit' or 'frail' will be randomised (ratio 1:1) to either immediate curative therapy (radiotherapy or prostatectomy) or conservative therapy (endocrine therapy or observation). Participants who are unable or unwilling to participate in randomisation will be enrolled in a separate observation group. Randomised patients will be followed for 10 years. TRIAL REGISTRATION: Ethics approval has been granted in Norway (457593), Denmark (H-22051998), Finland (R23043) and Sweden (Dnr 2023-05296-01). The trial is registered on Clinicaltrials.org (NCT05448547).

Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden.

INTRODUCTION: The use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life. METHODS AND ANALYSIS: PRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints. ETHICS AND DISSEMINATION: To implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05190172).

Cost-effectiveness analysis of a psychosocial web-based intervention for adolescents distressed by a visible difference: Results from a randomized controlled trial in Norway.

Adolescents with a visible difference to the face or body (e.g., due to a congenital condition, illness, or injury), may be at risk of elevated psychological distress. Young Person's Face IT (YPF), a web-based psychosocial intervention, has displayed effectiveness, but no previous study has specifically evaluated its cost-effectiveness. The aim of our study was to investigate whether YPF could be a cost-effective alternative for psychosocial support to adolescents distressed by a visible difference, relative to care-as-usual (CAU). Within the context of a randomized controlled trial in Norway, 102 participants (43% boys) were allocated to intervention (n = 55) or waiting list control group (n = 47). Mean age was 13.9 years (SD = 1.71; range 11-18), and all self-identified as experiencing distress related to a visible difference. Participants answered questionnaires including measures of health-related quality of life and social anxiety at baseline and 3-month follow-up. A health economic evaluation using the method of cost-utility analysis was performed, including quality-adjusted life-years (QALYs). Results indicated that the incremental cost-effectiveness of YPF was 63,641 Norwegian kroner per QALYs gained, which is well within the acceptability threshold in the Norwegian healthcare sector. Hence, YPF could potentially be considered a cost-effective intervention for adolescents experiencing distress related to a visible difference, but more research is needed that includes comparisons of YPF to other health- and societal resources and long-term follow-ups. Our study also constitutes an addition to research as, compared to interventions for somatic diseases, there is a lack of studies exploring the cost-effectiveness of psychological interventions.

Cost-Effectiveness of Noninvasive Screening for Alcohol-Related Liver Fibrosis.

BACKGROUND AND AIMS: Alcohol-related liver disease is often undetected until irreversible late-stage decompensated disease manifests. Consequently, there is an unmet need for effective and economically reasonable pathways to screen for advanced alcohol-related fibrosis. APPROACH AND RESULTS: We used real-world data from a large biopsy-controlled study of excessive drinkers recruited from primary and secondary care, to evaluate the cost-effectiveness of four primary care initiated strategies: (1) routine liver function tests with follow-up ultrasonography for test-positives, (2) the enhanced liver fibrosis (ELF) test with hospital liver stiffness measurement (LSM) for positives, (3) a three-tier strategy using the Forns Index to control before strategy 2, and (4) direct referral of all to LSM. We used linked decision trees and Markov models to evaluate outcomes short term (cost-per-accurate diagnosis) and long term (quality-adjusted life-years [QALYs]). For low-prevalence populations, ELF with LSM follow-up was most cost-effective, both short term (accuracy 96%, $196 per patient) and long term (incremental cost-effectiveness ratio [ICER] $5,387-$8,430/QALY), depending on whether diagnostic testing had lasting or temporary effects on abstinence rates. Adding Forns Index decreased costs to $72 per patient and accuracy to 95%. The strategy resulted in fewer QALYs due to more false negatives but an ICER of $3,012, making this strategy suited for areas with restricted access to ELF and transient elastography or lower willingness-to-pay. For high-prevalence populations, direct referral to LSM was highly cost-effective (accuracy 93%, $297 per patient), with ICERs between $490 and $1,037/QALY. CONCLUSIONS: Noninvasive screening for advanced alcohol-related fibrosis is a cost-effective intervention when different referral pathways are used according to the prevalence of advanced fibrosis. Patients in the primary health care sector should be tested with the ELF test followed by LSM if the test was positive, whereas direct referral to LSM is highly cost-effective in high-prevalence cohorts.

The Cost-Effectiveness of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer in Norway.

Background. Expansion of routine genetic testing for hereditary breast and ovarian cancer from conventional BRCA testing to a multigene test could improve diagnostic yield and increase the opportunity for cancer prevention in both identified carriers and their relatives. We use an economic decision model to assess whether the current knowledge on non-BRCA mutation prevalence, cancer risk, and patient preferences justifies switching to a multigene panel for testing of early-onset breast cancer patients. Methods. We evaluated routine testing by BRCA testing, a 7-gene panel, and a 14-gene panel using individual-level simulations of annual health state transitions over a lifetime perspective. Breast and ovarian cancer incidence is reduced and posttreatment survival is improved when high-risk mutations are detected and risk-reducing treatment offered. Most model inputs were synthesized from published literature. Intermediate health outcomes included breast and ovarian cancer incidence rates, along with organ-specific cancer mortality. Cost-effectiveness outcomes were health sector costs and quality-adjusted life years. Results. Intermediate health outcomes improved by testing with multigene panels. At a cost-effectiveness threshold of $77,000, a 7-gene panel test with five non-BRCA genes was the optimal strategy with an incremental cost-effectiveness ratio of $53,310 per quality-adjusted life year compared to BRCA-only testing. Limitations. Unable to stratify carriers to specific mutations within genes, we can only make predictions on the gene level, with combined risk estimates for known variants. As mutation prevalence is the absolute upper bound of returns to more expansive testing, the rarity of modelled mutations makes analysis outcomes sensitive to model implementation. Conclusions. A 7-gene panel to diagnose hereditary breast and ovarian cancer in early-onset breast cancer patients can be a cost-effective alternative to current BRCA-only testing in Norway.