Mechanisms of Progression and Challenges for Intervention in the Natural History of Early Prostate Cancer: A Narrative Review

Sandhu, Kieran, Pacey (Cambridge), Simon, Brewer, Daniel ORCID: https://orcid.org/0000-0003-4753-9794 and Gnanapragasam, Vincent J. (2026) Mechanisms of Progression and Challenges for Intervention in the Natural History of Early Prostate Cancer: A Narrative Review. Current Oncology. ISSN 1198-0052 (In Press)

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Abstract

Prostate cancer is the most common cancer diagnosed in men and the incidence is rising globally. Disease-related mortality however remains comparatively low. There is now irrefutable evidence that many men do not need treatment if diagnosed with early cancer and can instead be safely managed conservatively. Active surveillance is there-fore now an increasingly popular management option for these men. A minority of men on surveillance however will experience disease progression to a point where radical treatment is necessary. It is therefore logical to consider interventions that might slow down or abrogate this natural history. This is particularly important for subgroups of men with early cancer who are at a higher risk of progression and where the risk–benefit of therapeutic intervention is much more favourable. In this narrative review we explore the literature on known molecular and genetic events in prostate cancer which may drive progression. Our principal focus was to consider mechanisms that could be realistically targeted by therapeutics. We further consider key attributes that early cancer therapeutic trials should incorporate in their design. These include risk-stratified patient selection, bespoke dosing schedules and the importance of unambiguous, clinically meaningful endpoints in this new trial space.

Item Type:	Article
Uncontrolled Keywords:	prostate cancer,early disease,biology,active surveillance,therapeutics,disease progression,natural history,sdg 3 - good health and well-being,1* ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	LivePure Connector
Date Deposited:	07 Jul 2026 16:02
Last Modified:	07 Jul 2026 16:02
URI:	https://ueaeprints.uea.ac.uk/id/eprint/103775
DOI:	issn:1198-0052

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