Open AccessFeasibility of aspirin and/or vitamin D3 for men with prostate cancer on active surveillance with Prolaris® testing
Author(s) -
Dinneen Eoin,
Shaw Gregory L.,
Kealy Roseann,
Alexandris Panos,
Finnegan Kier,
Chu Kimberley,
Haidar Nadia,
SantosVidal Sara,
Kudahetti Sakunthala,
Moore Caroline M.,
Grey Alistair D. R.,
Berney Daniel M.,
Sahdev Anju,
Cathcart Paul J.,
Oliver R. Timothy D.,
Rajan Prabhakar,
Cuzick Jack
Publication year - 2022
Publication title -
bjui compass
Language(s) - English
Resource type - Journals
ISSN - 2688-4526
DOI - 10.1002/bco2.169
Subject(s) - medicine , prostate cancer , placebo , aspirin , population , clinical endpoint , prostate , biopsy , randomized controlled trial , vitamin d and neurology , urology , surgery , cancer , pathology , alternative medicine , environmental health
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.