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

Study Overview
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Brief Summary
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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. In all patients, 12 ml of blood sample will be collected in EDTA tube for analysis of biological biomarkers in different time points.

Detailed Description
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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.

Official Title
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An Exploratory proof-of Valid Biomarkers in Blood to Predict the Response to Therapy in Prostate Cancer Patients, a Single Center Study

Conditions
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Prostate Cancer

Intervention / Treatment
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* Other: biological samples collection and analysis


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 0 (set-up)<br>Patients with known diagnosis of CSPC (Group 0a) and CRPC (Group 0b) irrespective of the PC treatment (not first diagnosis) | Other: biological samples collection and analysis<br>* 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<br>|
| Group 1a (control)<br>Patients who underwent biopsies for suspected Prostate Cancer (PC), with a negative result for invasive cancer | Other: biological samples collection and analysis<br>* 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<br>|
| Group 1<br>Patients with a first diagnosis of localized biopsy-proven PC, untreated, planned to undergo radical surgery and / or radical radiotherapy | Other: biological samples collection and analysis<br>* 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<br>|
| Group 2<br>Patients with a diagnosis of locally advanced unresectable, recurrent or metastatic PC planned to receive first-line hormono therapy | Other: biological samples collection and analysis<br>* 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<br>|
| Group 3<br>Patients with recurrent/progressive/metastatic CRPC planned to receive chemotherapy | Other: biological samples collection and analysis<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers value in the response to therapy | 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 | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers inter and intra variability | to assess the inter- and intra-variability of the value of MDSCs, NLR and cytochines. | 3 years | 
| Metabolomic and metagenomic analysis | to set-up the microbiota analysis and blood analysis quantification and determine the intra- and inter-patient variability (Group 0); | 3 years | 
| Metabolomic and metagenomic analysis | 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 | 3 years |