Dataset Information

Feasibility of aspirin and/or vitamin D3 for men with prostate cancer on active surveillance with Prolaris® testing.

ABSTRACT:

Objectives

To test the feasibility of a randomised controlled trial (RCT) of aspirin and/or vitamin D3 in active surveillance (AS) low/favourable intermediate risk prostate cancer (PCa) patients with Prolaris® testing.

Patients and methods

Newly-diagnosed low/favourable intermediate risk PCa patients (PSA ≤ 15 ng/ml, International Society of Urological Pathology (ISUP) Grade Group ≤2, maximum biopsy core length <10 mm, clinical stage ≤cT2c) were recruited into a multi-centre randomised, double-blind, placebo-controlled study (ISRCTN91422391, NCT03103152). Participants were randomised to oral low dose (100 mg), standard dose (300 mg) aspirin or placebo and/or vitamin D3 (4000 IU) versus placebo in a 3 × 2 factorial RCT design with biopsy tissue Prolaris® testing. The primary endpoint was trial acceptance/entry rates. Secondary endpoints included feasibility of Prolaris® testing, 12-month disease re-assessment (imaging/biochemical/histological), and 12-month treatment adherence/safety. Disease progression was defined as any of the following (i) 50% increase in baseline PSA, (ii) new Prostate Imaging-Reporting and Data System (PI-RADS) 4/5 lesion(s) on multi-parametric MRI where no previous lesion, (iii) 33% volume increase in lesion size, or radiological upstaging to ≥T3, (iv) ISUP Grade Group upgrade or (v) 50% increase in maximum cancer core length.

Results

Of 130 eligible patients, 104 (80%) accepted recruitment from seven sites over 12 months, of which 94 patients represented the per protocol population receiving treatment. Prolaris® testing was performed on 76/94 (81%) diagnostic biopsies. Twelve-month disease progression rate was 43.3%. Assessable 12-month treatment adherence in non-progressing patients to aspirin and vitamin D across all treatment arms was 91%. Two drug-attributable serious adverse events in 1 patient allocated to aspirin were identified. The study was not designed to determine differences between treatment arms.

Conclusion

Recruitment of AS PCa patients into a multi-centre multi-arm placebo-controlled RCT of minimally-toxic adjunctive oral drug treatments with molecular biomarker profiling is acceptable and safe. A larger phase III study is needed to determine optimal agents, intervention efficacy, and outcome-associated biomarkers.

SUBMITTER: Dinneen E

PROVIDER: S-EPMC9579886 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Feasibility of aspirin and/or vitamin D3 for men with prostate cancer on active surveillance with Prolaris® testing.

Dinneen Eoin E Shaw Gregory L GL Kealy Roseann R Alexandris Panos P Finnegan Kier K Chu Kimberley K Haidar Nadia N Santos-Vidal Sara S Kudahetti Sakunthala S Moore Caroline M CM Grey Alistair D R ADR Berney Daniel M DM Sahdev Anju A Cathcart Paul J PJ Oliver R Timothy D RTD Rajan Prabhakar P Cuzick Jack J Cuzick Jack J Madaan Sanjeev S Pati Jhumur J Chowdhury Abdul M AM Birch Brian R P BRP Dudderidge Timothy J TJ Moore Caroline M CM Grey Alistair D R ADR Shaw Gregory L GL Jefferson Kieran P KP Kynaston Howard G HG Rajan Prabhakar P Green James S A JSA Cathcart Paul J PJ Berney Daniel M DM Powles Thomas T Oliver R Timothy D RTD Sahdev Anju A Kealy Roseann R Kemp Victoria V Alexandris Panos P Finnegan Kier K Chu Kimberly K

BJUI compass 20220611 6

<h4>Objectives</h4>To test the feasibility of a randomised controlled trial (RCT) of aspirin and/or vitamin D3 in active surveillance (AS) low/favourable intermediate risk prostate cancer (PCa) patients with Prolaris® testing.<h4>Patients and methods</h4>Newly-diagnosed low/favourable intermediate risk PCa patients (PSA ≤ 15 ng/ml, International Society of Urological Pathology (ISUP) Grade Group ≤2, maximum biopsy core length <10 mm, clinical stage ≤cT2c) were recruited into a multi-centre rando ...[more]

PMID: 36267207

Similar Datasets

Project description:Background & aimsFortification of the US food supply has increased folic acid intake and resulted in a concomitant decrease in neural tube defects in women. However, a body evidence supports the hypothesis that increased circulating folate levels due to excessive dietary or supplemental folic acid may be harmful for men with prostate cancer. Therefore, this pilot study aimed to investigate the feasibility of a reduced folic acid dietary intervention in men on an active surveillance monitoring program for prostate cancer.MethodsMen with low-grade prostate cancer enrolled into a 12-week dietary folic acid reduction diet. Primary outcome was red blood cell (RBC) folate reduction at 12 weeks. Other outcomes include serum folate, homocysteine, and vitamin B12 levels. The number of patients who complete the trial and reasons for disenrollment or dropout were also assessed.ResultsTwenty-eight participants were enrolled into the dietary intervention study. Six participants withdrew from the study and a total of 21 participants completed all baseline and week 12 biochemical assessments. Only 18 participants completed all dietary questionnaires. Participants withdrew from the study due to difficulty with the diet or personal reasons. A substantial reduction was noted in serum folate (p < 0.007), RBC folate (p < 0.001) and dietary consumption of folic acid from foods (p = 0.003) and supplements (p = 0.003) without reduction in serum homocysteine or vitamin B12. Although an overall decrease in PSA from baseline to twelve weeks was found, the reduction was not significant (-3.55 ng/mL, p = 0.197).ConclusionsThis phase 1 feasibility study reduced dietary folic acid intake from food and supplements and successfully lowered serum and RBC folate without resulting harmful effects. Data from this study supports future intervention trials with a larger prostate cancer active surveillance population and has the potential to reduce prostate cancer progression. There are no interventions to reduce progression of prostate cancer in man on active surveillance.

Project description:Initial management of intermediate-risk prostate cancer is evolving, with no clear recommendation for treatment. Data on utilization of active surveillance for patients with newly diagnosed intermediate-risk prostate cancer may help clarify emerging trends. To further characterize US national trends of initial management of intermediate-risk prostate cancer. This cohort study included patients with intermediate-risk prostate cancer diagnosed from January 1, 2010, to December 31, 2020. Eligible patients were diagnosed in US hospitals included in the National Cancer Database; National Comprehensive Cancer Network risk stratification guidelines were used to characterize as favorable vs unfavorable intermediate risk. Analysis was performed in September 2023. Active surveillance vs intervention with surgery and/or radiation or no treatment. Temporal trends in demographic, clinical, and socioeconomic factors among men with intermediate-risk prostate cancer and their association with the use of active surveillance; further subgroup analysis was conducted for those with favorable vs unfavorable intermediate risk classification. In total, 289 584 men diagnosed with intermediate-risk prostate cancer were identified from 2010 to 2020 (46 147 Black [15.9%], 230 071 White [79.5%]). Among patients, 153 726 (53.1%) underwent prostatectomy, 107 152 (37.0%) underwent radiotherapy, and 15 847 (5.5%) underwent active surveillance as initial treatment strategy. Overall, active surveillance quadrupled from 418 of 21 457 patients (2.0%) in 2010 to 2428 of 28 192 patients (8.6%) in 2020 for the entire cohort (P < .001). Active surveillance increased from 317 of 12 858 patients (2.4%) in 2010 to 2020 of 12 902 patients (13.5%) in 2020 in men with favorable intermediate-risk prostate cancer (P < .001). In the unfavorable intermediate-risk cohort, active surveillance increased from 101 of 8181 patients (1.2%) in 2010 to 408 of 12 861 patients (3.1%) in 2020 (P < .001). On multivariable analysis, use of active surveillance was associated with increased age (age 70-80 years vs <50 years: odds ratio [OR], 3.09; 95% CI, 2.66-3.59), lower Gleason score (3 + 3 vs 3 + 4: OR, 3.45; 95% CI, 3.25-3.66), early T stage (T2c vs T1a through T2a: OR, 0.35; 95% CI, 0.32-0.38), treatment at an academic center (community vs academic center: OR, 0.72; 95% CI, 0.67-0.78), higher level of education (communities with 21% or higher population without high school vs less than 7%: OR, 0.73; 95% CI, 0.67-0.79), insurance type (Medicare or other governmental service vs private: OR, 1.11; 95% CI, 1.07-1.16), proximity to treatment facility (greater than 120 miles vs less than 60 miles: OR, 0.75; 95% CI, 0.68-0.84), facility location (South Atlantic vs New England: OR, 0.54; 95% CI, 0.46-0.53), and lower income (less than $38 000 vs $63 000 or greater: OR, 1.22; 95% CI, 1.14-1.31). These findings highlight increasing implementation of active surveillance in the initial management of intermediate risk prostate cancer. Prospective data with improved risk stratification incorporating genomics and digital pathology artificial intelligence as well as novel surveillance strategies may continue to better delineate optimal treatment recommendations in this patient population.

Project description:ImportanceThe long-term outcomes among men with prostate cancer (PC) whose disease is managed with active surveillance (AS) remains unknown.ObjectiveTo develop a simulation model with a 30-year follow-up for men with PC managed with AS.Design, setting, and participantsIn this cohort study, a state transition model was created using data from Prostate Cancer data Base Sweden (PCBaSe) on 23 655 men diagnosed with PC and managed with deferred treatment to estimate treatment trajectories. A simulation was performed with 100 000 men in each combination of age at diagnosis, Charlson Comorbidity Index, and PC risk with a follow-up of 30 years.Main outcomes and measuresDeath from PC and death from other causes were estimated, and the proportion of time without active PC treatment was assessed until date of death or age 85 years.ResultsThis study included 23 655 men from PCBaSe with a median age at diagnosis of 69 years (IQR, 64-74 years). Of these, 16 177 men underwent active surveillance for PC and 7478 underwent watchful waiting. The proportion of men who were diagnosed at age 55 years and died of PC before age 85 years was 9% for very low-risk PC, 13% for low-risk PC, and 15% for intermediate-risk PC. Among men with a Charlson Comorbidity Index of 0 who were diagnosed at age 70 years, the corresponding percentages were 3%, 6%, and 7%, respectively. The mean proportion of remaining life-years without active PC treatment for men diagnosed at age 55 years was 12 of 25 years (48%) for very low-risk PC, 9 of 25 years (36%) for low-risk PC, and 7 of 25 (29%) for intermediate-risk PC. For men aged 70 years, the corresponding numbers were 10 of 13 years (77%), 9 of 13 years (66%), and 8 of 13 years (60%), respectively. Men with intermediate-risk PC who were younger than 60 years at diagnosis had a high risk of PC death (12%-15%) and fewer remaining life-years without active PC treatment (29%-33%). In contrast, men with low-risk PC who were older than 65 years at diagnosis had a lower risk of PC death (3%-5%) and more remaining life-years without active PC treatment (62%-77%).Conclusions and relevanceThe findings of this Swedish cohort study suggest that active surveillance may be a safe strategy for disease management among men with PC who were older than 65 years at diagnosis.

Project description:Clinical trials play a critical role in evidence-based medicine, when rigorous scientific methodology is utilized to discover and test the effectiveness and safety of new drugs to prevent or cure diseases, including cancer. Participation in clinical trials thus becomes key to successful completion of these trials. Although it is estimated that >70% of Americans are inclined to participate in clinical trials, less than 5% of adult cancer patients participate in clinical trials. There is thus a large gap between those inclined to participate in clinical trials and actual participation in clinical trials. As with trials targeting men with prostate cancer (PCa) on active surveillance (AS), where the target population is mostly over 50 years of age, others have observed several challenges with recruitment and accrual in clinical trials. The participation rate is currently unavailable for men on primary and secondary chemoprevention trials. Additionally, with unanticipated environmental factors such as a pandemic or other natural emergencies that may severely impact the economy, personal property, travel and person-to person contact for study-related procedures, there is a need to continuously identify these challenges and determine solutions to recruitment barriers in chemoprevention trials to ensure timely completion of early phase trials. Recent studies regarding the impact of the pandemic on clinical trial recruitment have shown that cancer prevention trials were relatively more negatively impacted compared to cancer treatment trials. The goal of this manuscript is to review our experience in continuously evaluating the protocol and patient level challenges to recruiting subjects on AS for PCa in this cancer chemoprevention trial conducted at the Comprehensive Cancer Center (CCC) and report the contemporary strategies that we are utilizing to continue to recruit subjects in this trial. We provide data from our current trial as an example while discussing future strategies to improve overall clinical trial recruitment. These strategies can inform future design of contemporary cancer chemoprevention trials and, additionally, better select, focus and invest in strategies that are the most productive and efficient for recruiting target populations.

Project description:BackgroundThe prognosis for men with non-aggressive prostate cancer is good, and several studies have investigated the impact of lifestyle changes including physical activity and diet on the prognosis. Despite positive results in animal studies and a few human interventions with whole-grain rye on markers of prostate cancer progression, the feasibility of trials investigating such dietary changes in combination with physical activity remains largely unstudied. The primary aim was to investigate the feasibility of an intervention with high whole-grain rye intake and vigorous physical activity for 6 months in men diagnosed with prostate cancer.MethodsIn total, 26 men (53-72 years) recently diagnosed with non-aggressive prostate cancer and on active surveillance, were enrolled in 2011-2012 and randomly assigned to an intervention or a control group. The intervention included 170 g/day of whole-grain rye and 3 × 45 minutes/week of vigorous physical activity. The duration of the intervention was 6 months and end of follow-up 12 months after baseline. Clinic visits were scheduled at baseline and 3, 6 and 12 months after baseline. Compliance with the intervention was evaluated by diaries, food frequency questionnaires, biomarkers, and heart rate monitor data. The effect of the intervention was evaluated by linear multiple regression analysis.ResultsIn the intervention group, the mean daily intake of whole-grain rye measured from diaries was 146 g (SD: 19) for the first 3 months and 125 g (SD: 40) for the last 3 months of the intervention. The median level (5th and 95th percentiles) of vigorous physical activity was 91 (17, 193) min/week for the first 3 months and 66 (13, 259) min/week for the last 3 months. No recordings of physical activity were done for the control group. Aerobic fitness (VO2 peak) increased in the intervention group compared to the control group after the intervention. No effects were found on other cardio-metabolic outcomes or prostate cancer progression.ConclusionsThe lifestyle intervention appeared feasible for 6 months among Danish men and the results are encouraging for conducting full-scale studies, where the impact of whole-grain rye and vigorous physical activity on prostate cancer progression and metabolic parameters can be evaluated.Trial registrationClinicalTrials.gov, NCT01300104 . Registered on 18 February 2011.

Dataset Information

Feasibility of aspirin and/or vitamin D3 for men with prostate cancer on active surveillance with Prolaris® testing.

Objectives

Patients and methods

Results

Conclusion

Publications

Feasibility of aspirin and/or vitamin D3 for men with prostate cancer on active surveillance with Prolaris® testing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets