ERG rearrangement status and castration resistant prostate cancer : a prospective,population-based study

• Overtreatment is a major concern in prostate cancer (PCa) management, as no adequate prognostic tool exists to separate indolent from aggressive disease at time of diagnosis. Androgen deprivation therapy (ADT) is the standard treatment of locally recurrent or metastatic PCa and although most men respond well to ADT initially, inevitably a resistance to the treatment develops. Men with tumor growth despite the androgen-depleted environment are considered to have castration resistant PCa (CRPC). After developing CRPC, the median survival time is typically less than two years. Since the initial discovery of ERG rearrangement in PCa, several studies have investigated the association between ERG rearrangement and clinical outcome of PCa with discrepant results. Few studies have examined the association between ERG rearrangement and CRPC, despite the fact that the most common fusion partners to ERG are androgen regulated. In this study we investigated the association between ERG status and time to CRPC.We assessed the ERG status in a cohort of 220 men initially managed by watchful waiting and treated with ADT at disease progression. There was no statistically significant association between ERG status and time from start of ADT to CPRC, or start of ADT to PCa-specific death. However, men harboring the ERG rearrangement did have a significantly shorter time between time of diagnosis and start of hormonal treatment, compared to men without the rearrangement (HR: 1.81; 95% CI: 1.23- 2.65), suggesting that ERG rearrangement is indicative of a more aggressive subtype of PCa./p>

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