Prostate cancer has the highest incidence and is the second leading cause of cancer death in men in western countries. Androgen deprivation therapy is the backbone treatment. However, after a latency hormone sensitive prostate cancer (HSPC) usually progresses to castration-resistant prostate cancer (CRPC) requiring treatments including next generation hormonal therapies with Abiraterone Acetate (AA). This, with limited survival. A particularly challenging area of interest to improve outcome in cancer is the interaction between the microbiome and anti-cancer therapies. Emerging data demontrate in pre-clincal studies that prostate cancer alters the microbiota, with loss of diversity and depletion of beneficial bacteria including A. muciniphila. In the other hand, Androgen deprivation therapy, reverses these effects. Specifically, in advanced disease with castration-resistant prostate cancer (CRPC), it has been shown in small studies that Abiraterone Acetate, can modulate patient-associated gastro-intestinal microbiota through promoting the growth of A. muciniphila. The goal of our study is to confirm that AA could promote fecal Akkermansia muciniphila growth and to use the enrichment of fecal Akkermansia muciniphila as a minimally invasive biomarker of response to AA in first line metastatic CRPC.
Study Type
OBSERVATIONAL
Enrollment
52
Plasma sampling ans stool sampling * at inclusion * at 1 month * at 3 months * at progression within the 3 months
Hôpital Saint Louis AP-HP
Paris, France
RECRUITINGRelative abundance of Akkermansia muciniphila
Between baseline and Month 1 of next-generation hormonotherapy (NGHT), compared between responders versus non-responders. The response is defined as an early PSA decrease \> 50% at one month of NGHT.
Time frame: At 1 month
Relative variation of the relative abundance of Akkermansia muciniphila
Between baseline and Month 3 of AA treatment, compared between responders versus non responders
Time frame: At 3 months
Relative variation in PSA
Relative variation in PSA between baseline PSA and nadir value, according to fecal Akkermansia muciniphila enrichment
Time frame: At 1 month
Receiver Operating curve (ROC)
Receiver Operating curve (ROC) of the baseline relative abundance of fecal Akkermansia muciniphila to predict PSA response
Time frame: At 1 month
Receiver Operating curve (ROC)
Receiver Operating curve (ROC) of the baseline relative abundance of fecal Akkermansia muciniphila to predict PSA response
Time frame: At 3 months
PSA progression-free (PSA-PFS) survival
According to fecal Akkermansia muciniphila baseline relative abundance. PSA-PFS will be defined as the time from treatment initiation to PSA progression as per PCWG3 (The Prostate Cancer Working Group 3) or death, whichever occurs first; patients without event at M3 will be treated as censored observations.
Time frame: At 3 months
Anti- Akkermansia muciniphila IgG levels
Time frame: At baseline
Anti- Akkermansia muciniphila IgG levels
Time frame: At 1 month
Anti- Akkermansia muciniphila IgG levels
Time frame: At 3 months
Anti- Akkermansia muciniphila IgA levels
Time frame: At baseline
Anti- Akkermansia muciniphila IgA levels
Time frame: At 1 month
Anti- Akkermansia muciniphila IgA levels
Time frame: At 3 months
Alpha diversity
Assessed by Shannon index (Microbial Richness)
Time frame: At baseline
Alpha diversity
Assessed by Shannon index (Microbial Richness)
Time frame: At 1 month
Alpha diversity
Assessed by Shannon index (Microbial Richness)
Time frame: At 3 months
Beta diversity
Assessed by Bray-Curtis dissimilarity (Microbial Diversity)
Time frame: At baseline
Beta diversity
Assessed by Bray-Curtis dissimilarity (Microbial Diversity)
Time frame: At 1 month
Beta diversity
Assessed by Bray-Curtis dissimilarity (Microbial Diversity)
Time frame: At 3 months
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