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Clinical Studies

High-dose vitamin D supplementation and prostate cancer progression: a phase II randomised trial in localised prostate cancer cases with intermediate risk of progression (ProsD)

British Journal of Cancer volume 134, pages 735–745 (2026)Cite this article

Subjects

This article has been updated

Abstract

Background

The ProsD trial aimed to determine if oral vitamin D supplementation could prevent prostate cancer (PC) progression in men on active surveillance (AS).

Methods

ProsD is a phase-II double-blinded randomized trial of newly diagnosed, low-intermediate risk PC cases, aged between 50 and 80 years and on AS. The intervention was a monthly oral dose of cholecalciferol (50,000IU; Vitamin D) or placebo. Primary and secondary endpoints were active therapy-free (ATFS) and progression-free (PFS) survival, respectively. Blood samples were analysed for vitamin D metabolites and cytokinesis-block micronucleus cytome (CBMN) markers for lymphocytic genome damage.

Results

There were 123 randomised participants (81 vitamin D and 42 placebo) included in this analysis. Mean (SD) for age was 66.5 (6.6) years and for 25(OH)D levels were 72.0 (19.9) and 66.4 (18.4) nmol/L at baseline (p = 0.1), and 91.9 (19.9) and 60.4 (24.4) nmol/L at 24 months, in the vitamin D and placebo arms respectively. There were no appreciable differences in ATFS (plog-rank = 0.44), PFS (p plog-rank = 0.60) and occurrence of adverse events, in each trial arm. There were declines in some of the lymphocytic CBMN markers in the vitamin D arm.

Conclusion

Vitamin D supplementation did not prevent PC progression, although reduced prevalence of CBMN markers may indicate a benefit of vitamin D supplementation.

Trial registration

Australia New Zealand Clinical Trials Registry (ACTRN12616001707459).

Key points

  • Findings: In this phase 2 randomised trial involving 123 prostate cancer patients with low-intermediate risk of progression, vitamin D supplementation did not prevent patients discontinuing active surveillance in favour of active therapy. However, vitamin D supplementation reduced prevalence of lymphocytic genome damage markers that are predictors of cancer risk.

  • Meaning: Vitamin D supplementation may not prevent progression of well-developed prostate cancers, however reduction in the prevalence of lymphocytic genome damage in the vitamin D arm of the study suggests an anti-cancer effect that may prevent the initiation of new cancers.

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Fig. 1: Consort diagram of ProsD participants.
Fig. 2: Kaplan Meir plot of ATFS by treatment group for vitamin D (n = 81) and placebo (n = 42).
Fig. 3: Kaplan Meir plot of PFS by treatment group for vitamin D (n = 81) and placebo (n = 42).
Fig. 4: Follow-up trends in plasma vitamin D metabolites across treatment groups.

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Data availability

Deidentified participant data will be made available after publication of trial findings. Please email corresponding author (visalinin@nswcc.org.au) for data regarding this clinical trial or codes used to generate the results, whereby this information will be released in compliance with institutional policy.

Change history

  • 26 February 2026

    In this article the orientation of tab 2 has been changed.

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Acknowledgements

We would like to thank all our trail participants and their families for their participation and cooperation in adhering to trial requirements, to our consumers Mr Con Casey and Mr John Goodall for thier input in designing this trial, Ms J Rodger and Ms R Foo for trial management, Ms K Willis, Mr Ishan Shalliker and Dr Mashreka Sarwar for volunteering in trial administration, Ms Maryam Hor (CSIRO) for the processing of all blood samples, Dr Marzieh Amirmostofian for developing and validating the assay for the vitamin D metabolites and Ms Rebecca Sawyer for doing the 1,25(OH)2D assays. We would also like to thank pathology providers (Sonic Healthcare, Laverty Pathology), radiology providers (IMED, PRP Imaging), and Marken for the transportation of biospecimens.

Funding

This work was funded by the Movember Clinical Trials Award and administered through the Prostate Cancer Foundation Australia (CTA1315).

Author information

Authors and Affiliations

  1. The Daffodil Centre, The University of Sydney, and Cancer Council NSW, Sydney, NSW, Australia

    Visalini Nair-Shalliker & David P. Smith

  2. Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia

    Visalini Nair-Shalliker, David Gillatt & Howard Gurney

  3. School of Public Health and Preventive Medicine, Monash University, Clayton, VIC, Australia

    David P. Smith, Manish I. Patel & James Symons

  4. NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia

    Val Gebski & David Espinoza

  5. Specialty of Surgery, Westmead Hospital, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

    Manish I. Patel

  6. Department of Surgery, Monash University, Cabrini Institute, Cabrini Health, Clayton, VIC, Australia

    Mark Frydenberg

  7. Royal Brisbane and Women’s Hospital, Herston, QLD, Australia

    John Yaxley

  8. University of Queensland, St Lucia, QLD, Australia

    John Yaxley & Robert ‘Frank’ Gardiner

  9. Bond University, Robina, Queensland, Australia

    Michael G. Kimlin

  10. Clinical and Health Sciences, University of South Australia, Sydney, SA, Australia

    Varinderpal Dhillon, Michael Fenech & Paul H. Anderson

  11. The Commonwealth Scientific and Industrial Research Organisation (CSIRO), Health & Biosecurity, Human Health Program, Sydney, SA, Australia

    Wayne Leifert

  12. Department of Urology, Blacktown Hospital, Sydney, NSW, Australia

    Henry Woo

  13. Department of Uro-Oncology, Chris O’Brien Lifehouse, Camperdown, Sydney, NSW, Australia

    Henry Woo

  14. Royal North Shore Hospital, Sydney, NSW, Australia

    Krishan Rasiah

  15. Urology Centre Port Macquarie, Sydney, NSW, Australia

    Nader Awad

  16. University of New South Wales, Rural School of Medicine, Port Macquarie, Sydney, NSW, Australia

    Nader Awad

  17. Sydney Adventist Hospital, NSW, Sydney, Australia

    James Symons

  18. Children’s Medical Research Institute, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia

    Jadon K. Wells & Hilda A. Pickett

  19. School of Public Health, The University of Western Australia, Perth, WA, Australia

    Bruce K. Armstrong

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  1. Visalini Nair-Shalliker
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Contributions

HG is the principal investigator of ProsD; VN-S, MF and BKA conceived the initial concept of this trial and in conjunction with HG, DPS, MIP, JWY, MF, DG, RG and MGK developed the rationale for this trial; VN-S and HG led the development of the trial protocol and drafted this manuscript; VN-S and DPS were involved in coordinating all aspects of this trial, data collection and management; VG and DE were responsible for the statistical design of the trial, protocol development and setup the IVRS system for blinding and randomising participants; MF and VD helped with the interpretation of the genome damage assays; MIP, MaF, JWY, DG, HW, KR, NA and JS contributed t recruiting high volume of participants to this trial; PHA analysed all samples for vitamin D metabolites and HP and JW undertook telomere analysis; All authors have contributed to the development of the study protocol and this manuscript. Coordinating centre: Dr Nair-Shalliker and A/Prof Smith at Cancer Council NSW coordinated all aspects of this trial. They contributed to study design and protocol development, data collection, management, analysis, interpretation of results, writing of the report, and the decision to submit the report for publication. Steering committee: Professor Gurney, Dr Nair-Shalliker, A/Prof Smith, Professor Patel, Professor Woo, Professor Gebski, Mr Espinoza, Professor Yaxley, Professor Gardiner, Professor Frydenberg and Professor Gillatt, all contributed to the study design, decision making, interpretation of data, writing of the report, and the decision to submit the report for publication. Independent Data Monitoring and Safety Committee: Dr Hayden, A/Prof Wilcken and Dr Asher. Data Management team: Dr Nair-Shalliker, A/Prof Smith, Ms Rodger and Ms Foo. Blinding and Randomisation of participants: Professor Gebski and Mr Espinoza from the NHMRC Clinical Trials Centre setup the Interactive Voice Response System (IVRS) for blind randomisation of participants. Blood collection, transportation and processing: All participants were requested to attend their nearest Sonic Healthcare pathology for blood sampling. Blood specimens collected to monitor PSA levels were sent to the Sonic central processing laboratory for analysis. Blood specimens collected for the purpose of the trial, were transported by Marken Australia to the processing laboratory. The Commonwealth Scientific and Industrial Research Organisation (CSIRO-Adelaide) was responsible for processing and storing all blood specimens for analysis at end of trial. Pharmaceutical manufacture and packaging: Vitamin D supplements and placebo were initially manufactured and packaged by API Consumer Brands (NZ). A second batch was manufactured by BioTech Pharmacal Inc (USA) and packaged by PCI Pharma (Australia).

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Correspondence to Visalini Nair-Shalliker.

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Nair-Shalliker, V., Smith, D.P., Gebski, V. et al. High-dose vitamin D supplementation and prostate cancer progression: a phase II randomised trial in localised prostate cancer cases with intermediate risk of progression (ProsD). Br J Cancer 134, 735–745 (2026). https://doi.org/10.1038/s41416-025-03278-w

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