Jean-Philippe Emond1, Louis Lacombe1, Patrick Caron2, Véronique Turcotte2, David Simonyan3, Armen Aprikian4, Fred Saad5, Michel Carmel6, Simone Chevalier4, Chantal Guillemette7, Eric Lévesque8. 1. Centre Hospitalier Universitaire (CHU) de Québec Research Center and Faculty of Medicine, Laval University, Québec, Canada. 2. CHU de Québec Research Center and Faculty of Pharmacy, Laval University, Québec, Canada. 3. Statistical and Clinical Research Platform, CHU de Québec Research Center, Québec, Canada. 4. McGill University Health Center, McGill University, Faculty of Medicine, Québec, Canada. 5. Centre Hospitalier de l'Université de Montréal, Université de Montréal, Québec, Canada. 6. Université de Sherbrooke, Faculty of Medicine, Québec, Canada. 7. CHU de Québec Research Center and Faculty of Pharmacy, Laval University, Québec, Canada. chantal.guillemette@crchudequebec.ulaval.ca. 8. Centre Hospitalier Universitaire (CHU) de Québec Research Center and Faculty of Medicine, Laval University, Québec, Canada. eric.levesque@crchudequebec.ulaval.ca.
Abstract
BACKGROUND: Prostate cancer (PCa) is the most common cancer in North American men. Beyond the established contribution of androgens to disease progression, growing evidence suggest that oestrogen-related pathways might also be of clinical importance. The aim of this study was to explore the association of urinary oestrogen levels with clinical outcomes. METHODS: Urine samples from the prospective multi-institutional PROCURE cohort were collected before RP for discovery (n = 259) and validation (n = 253). Urinary total oestrogens (unconjugated + conjugated), including oestrone and oestradiol, their bioactive and inactive catechol and methyl derivatives (n = 15), were measured using mass spectrometry (MS). RESULTS: The median follow-up time for the discovery and replication cohorts was 7.6 and 6.5 years, respectively. Highly significant correlations between urinary oestrogens were observed; however, correlations with circulating oestrogens were modest. Our findings indicate that higher levels of urinary oestriol and 16-ketoestradiol were associated with lower risk of BCR. In contrast, higher levels of 2-methoxyestrone were associated with an increased risk of development of metastasis/deaths. CONCLUSIONS: Our data suggest that urinary levels of oestriol and 16-ketoestradiol metabolites are associated with a more favourable outcome, whereas those of 2-methoxyestrone are associated with an elevated risk of metastasis after RP. Further studies are required to better understand the impact of oestrogens on disease biology and as easily accessible urine-based risk-stratification markers.
BACKGROUND: Prostate cancer (PCa) is the most common cancer in North American men. Beyond the established contribution of androgens to disease progression, growing evidence suggest that oestrogen-related pathways might also be of clinical importance. The aim of this study was to explore the association of urinary oestrogen levels with clinical outcomes. METHODS: Urine samples from the prospective multi-institutional PROCURE cohort were collected before RP for discovery (n = 259) and validation (n = 253). Urinary total oestrogens (unconjugated + conjugated), including oestrone and oestradiol, their bioactive and inactive catechol and methyl derivatives (n = 15), were measured using mass spectrometry (MS). RESULTS: The median follow-up time for the discovery and replication cohorts was 7.6 and 6.5 years, respectively. Highly significant correlations between urinary oestrogens were observed; however, correlations with circulating oestrogens were modest. Our findings indicate that higher levels of urinary oestriol and 16-ketoestradiol were associated with lower risk of BCR. In contrast, higher levels of 2-methoxyestrone were associated with an increased risk of development of metastasis/deaths. CONCLUSIONS: Our data suggest that urinary levels of oestriol and 16-ketoestradiol metabolites are associated with a more favourable outcome, whereas those of 2-methoxyestrone are associated with an elevated risk of metastasis after RP. Further studies are required to better understand the impact of oestrogens on disease biology and as easily accessible urine-based risk-stratification markers.
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