Valid Biomarkers in Blood to Predict the Response to Therapy in Prostate Cancer Patients

Participants to the study will be assigned to 5 cohorts according to the stage of disease and planned antitumor treatment at time of study entry.

Group 0 (set-up): blood sampling and rectal swab will be collected at a single time-point during the PC treatment. No follow-up is required.

Group 1a (control): the first blood sampling will be performed within 4 weeks since the negative biopsy; subsequent samplings will be done according to a schedule comparable to that of Group 1 up to 1 year or evidence of tumor, whichever occurs first.

Group 1, Group 2 and Group 3: the first blood sampling will be performed before radical treatment or HT start or CT start, on the basis of the planned antitumor therapy; subsequent sampling will be done after radical intervention at 4 weeks (only for Group 1) and then every 3 months (or more frequently if clinically indicated), up to 3 years or evidence of tumor recurrence/progression (radiological or biochemical), whichever occurs first.

At the time of recurrence/progression, patients of Group 1 could become part and could be followed as per Group 2, and patients of Group 2 could become part and could be followed as per Group 3.

Group Exo and Group Bio: blood sampling will be performed at a single time-point during the PC treatment. No follow-up is required.

• biological samples collection and analysis (Other): Participants to the study will be assigned to 4 cohorts according to the stage of disease and planned antitumor treatment at time of study entry; they will be followed up and sampled according to a defined time schedule

Primary outcomes

• Biomarkers value in the response to therapy [3 years]: To assess the value of MDSCs, NLR, cytokines as biomarkers of clinical outcome at different stages of disease and their correlation with PSA, the marker usually used for PC

Secondary outcomes

• Biomarkers inter and intra variability [3 years]: to assess the inter- and intra-variability of the value of MDSCs, NLR and cytochines.
• Metabolomic and metagenomic analysis [3 years]: to set-up the microbiota analysis and blood analysis quantification and determine the intra- and inter-patient variability (Group 0);
• Metabolomic and metagenomic analysis [3 years]: to assess the diversity and the composition of the intestinal microbiota and its blood metabolites in PC patients in castration-sensitive (Group 2) and castration-resistant (Group 3) phase

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

General inclusion criteria (for entering all groups)

* Age ≥ 18 years
* Histological diagnosis of prostate adenocarcinoma at different stages of disease (see Section 6.2) for which a treatment is indicated
* Written Informed Consent

Inclusion criterion only for entering Group 0

• Patients with a known diagnosis of CSPC or CRPC

Inclusion criterion only for entering Group 1a

• Patients that underwent biopsies for a suspect of PC, but resulted negative for cancer

Exclusion Criteria:

General exclusion criteria (for entering all groups)

* Active infection requiring treatment
* Decrease of general condition
* Concomitant severe comorbities
* Difficult socioeconomic conditions making regular follow up unfeasible.
* Need of concomitant steroids at study entry and during the study
* Diagnosis of second tumor in the previous 5 years

Exclusion criterion only for entering Group 0

• No antibiotic treatments in the previous 2 months before enrollment

Exclusion criteria only for entering Group 1

* Previous radical surgery and / or radical radiotherapy
* Previous hormonal treatments

Exclusion criteria only for entering Group 2

* No antibiotic treatments in the previous 2 months before enrollment (only in patients enrolling also for metagenomics and metabolomics)
* Previous hormonal treatments for advanced disease

Exclusion criterion only for entering Group 3

• No antibiotic treatments in the previous 2 months before enrollment (only in patients enrolling also for metagenomics and metabolomics analyses)

• Ricardo Pereira Mestre, MD, Principal investigator, Oncology Institute of Southern Switzerland (IOSI)