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

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

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.

Study Overview

• Status: Completed
• Conditions: Death; Metastasis; Castration-resistant Prostate Cancer
• Intervention / Treatment: Diagnostic test: Free PSA ratio test in patients after definitive treatment for localized prostate cancer

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 822

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2M9
      • Princess Margaret Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

All patients in Princess Margaret Cancer treated for localized adenocarcinoma of the prostate between 2000 and 2017 with either radical prostatectomy or radiotherapy with a rising post-treatment PSA, who had at least one post-treatment free PSA blood test.

Description

Inclusion Criteria:

For the two retrospective cohorts:

1. All patients that older than 18 treated for localized adenocarcinoma of the prostate between 2000 and 2017 with either radical prostatectomy or radiotherapy
2. 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:

1. Patients that were younger than 18,
2. Patients with prostate cancer other than adenocarcinoma, such as small cell and neuroendocrine cancer
3. Patients with prostate adenocarcinoma that did not develop biochemical recurrence.
4. In the retrospective cohorts - patients that did not have at least one post-treatment free PSA blood test.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Radical prostatectomy (RP cohort); 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; 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; 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; Free PSA ratio blood test done on biobank samples of patients after radical prostatectomy who developed biochemical recurrence.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Collaborators: University of Toronto
• Investigators: Study Director: Neil Fleshner, MD, MPH, Princess Margaret Hospital, University Health Network

Publications and helpful links

General Publications

• Goldberg H, Glicksman R, Woon D, Hoffman A, Shaikh H, Chandrasekar T, Klaassen Z, Wallis CJD, Ahmad AE, Sanmamed-Salgado N, Qu X, Moraes FY, Diamandis EP, Berlin A, Fleshner NE. Can post-treatment free PSA ratio be used to predict adverse outcomes in recurrent prostate cancer? BJU Int. 2021 Jun;127(6):654-664. doi: 10.1111/bju.15236. Epub 2020 Sep 26.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): December 30, 2018
• Study Completion (Actual): April 10, 2019

Study Registration Dates

• First Submitted: April 19, 2019
• First Submitted That Met QC Criteria: April 22, 2019
• First Posted (Actual): April 25, 2019

Study Record Updates

• Last Update Posted (Actual): April 25, 2019
• Last Update Submitted That Met QC Criteria: April 22, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Disease Attributes; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Recurrence
• Other Study ID Numbers: 17-5498

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No