Prognostic Role of Free Psa Ratio at Biochemical Recurrence After Radical Treatments for Prostate Cancer

Study Overview
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Brief Summary
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Measurement of Free PSA ratio in patients after definitive radical treatment for prostate cancer, and assessment of whether post-treatment free PSA ratio can function as a biomarker for advanced disease in prostate cancer patients.

Detailed Description
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Prostatic specific antigen (PSA) circulates mostly in complex with protease inhibitors, but 10-30% circulates as inactive free-PSA (FPSA). In patients with prostate cancer (PCa), pretreatment FPSA is lower and used to risk-stratify patients for biopsy. However, posttreatment FPSA ratio (FPSAR) is rarely quantified, with an unexplored clinical value. Methods The institutional database was queried to identify patients following radical prostatectomy (RP cohort) or radiotherapy (RT cohort) between 2000 and 2017. For validation, the investigators identified an independent prospective cohort with biochemical recurrence (BCR) after RP, using biobank samples (biobank cohort). All patients had at least one posttreatment FPSAR test. Kaplan-Meier (KM) method was used to compare the metastasis-free (MFS), castration-resistant PCa (CRPC)-free, and cancer-specific-survival (CSS) rates. Multivariable Cox models determined the association between posttreatment FPSAR, metastases, and CRPC.

Official Title
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An Old Biomarker That Can Learn New Tricks: Prognostic Role of Free Psa Ratio at Biochemical Recurrence After Radical Treatments for Prostate Cancer

Conditions
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Metastasis, Castration-resistant Prostate Cancer, Death

Intervention / Treatment
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* Diagnostic Test: Free PSA ratio test in patients after definitive treatment for localized prostate cancer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For the two retrospective cohorts: All patients that older than 18 treated for localized adenocarcinoma of the prostate between 2000 and 2017 with either radical prostatectomy or radiotherapy All treated patients had a rising post-treatment PSA, with at least one post-treatment free PSA blood test. For the biobank validation cohort: 1. All patients treated with radical prostatectomy for localized prostate cancer between 2000 and 2017 who had biobank samples taken when developing biochemical recurrence. Exclusion Criteria: Patients that were younger than 18, Patients with prostate cancer other than adenocarcinoma, such as small cell and neuroendocrine cancer Patients with prostate adenocarcinoma that did not develop biochemical recurrence. In the retrospective cohorts - patients that did not have at least one post-treatment free PSA blood test.

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 |
| --- | --- |
| Radical prostatectomy (RP cohort)<br>Our institutional prostate cancer database was queried for all patients between 2000-2017 who had a biochemical recurrence (BCR) after radical prostatectomy (RP) (Total PSA>=0.2 ng/ml) and had at least one post-BCR free PSA ratio (FPSAR) blood test (RP cohort). FPSAR ascertainments were performed incidentally or reflexively (e.g. PSA in the range of 4-10 ng/ml, as per Institutional policy). If multiple FPSAR tests were performed, only the first FPSAR test was analyzed. otal PSA and Free PSA data was performed with the Abbott Architect analytical platform, according to the instructions of the manufacturer. | |
| Radiotherapy cohort<br>Our institutional database was queried or all patients between 2000-2017 who had a rising PSA after radiotherapy (RT) for intermediate- and high-risk prostate cancer, and at least one post-treatment free PSA ratio (FPSAR) blood test (RT cohort). As in the RP cohort, FPSAR was performed either incidentally or reflexively, and the first FPSAR test was used for the analyses. Total PSA and Free PSA data was performed with the Abbott Architect analytical platform, according to the instructions of the manufacturer. | |
| Biobank surgical cohort<br>To validate our findings in the two retrospective cohorts (RP and RT), we analyzed a third cohort of prospectively collected biobank specimens of patients who underwent RP and developed biochemical recurrence(Biobank cohort). The retrieved samples were batched and tested for FPSAR levels to determine the results in lower PSA ranges and also to account for intrinsic analyte measurements variability in the retrospective cohorts. For his cohort we used the Roche Elecsys analytical platform, according to the instructions of the manufacturer. | Diagnostic Test: Free PSA ratio test in patients after definitive treatment for localized prostate cancer<br>* Free PSA ratio blood test done on biobank samples of patients after radical prostatectomy who developed biochemical recurrence.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metastasis free survival | Rate of Metastasis correlated to the first post-treatment free PSA ratio | From date of diagnosis to date of Metastasis development, assessed up to 200 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Castrate resistant prostate cancer (CRPC) free survival | Rate of CRPC correlated to the first post-treatment free PSA ratio | From date of Diagnosis to date of CRPC development, assessed up to 200 months | 
| Cancer specific survival | Rate of Cancer specific survival correlated to the first post-treatment free PSA ratio | From date of diagnosis to date of cancer specific death, assessed up to 200 months |