Prostate-Specific Antigen /BloodNCT03978299
Factors Associated With PSA False Negative and False Positive Results and the Impact on Patient's Health.
An observational study of Prostate-Specific Antigen /Blood, run by Universidad Miguel Hernandez de Elche at 2 sites in Spain.
Trial summary
Objectives: The primary aim of this study is to evaluate the outcomes of the determination of PSA for the early detection of prostate cancer or in the presence of symptoms, in general practice in two health departments of the Valencian Community (Spain). Specific objectives: 1. Read more about this study
- Who is it for?
- Ages 18 to 99 years, men only
- Conditions the study is for
- Prostate-Specific Antigen /Blood
- What is being tested?
- Positive Prostate-Specific Antigen test result
- How many people
- 2,527 participants
- Where
- 2 sitesSpain
- Study dates
- 18 Jul 2018to Jul 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: Men over 18 from the Health Department 17 and 19, in the Valencian Community (these include General University Hospital of Sant Joan d'Alacant and General University Hospital of Alicante, respectively). These are referral hospitals for all individuals living in their catchment areas and belong to the National Health Care System (the majority of the population in Spain uses the National Health System (NHS) as the main medical service (the publicly funded insurance scheme covers 98.5% of the Spanish population). The investigators have not established maximum age limit.
Who may be able to join
- Patients with a PSA determination result in a routine health examination from the Health Department 17 and 19, in the Valencian Community (Spain)
Who cannot join
- Patients who have been previously diagnosed with prostate cancer.
- Patients who are being followed for previous high PSA values.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites, 2 recruiting
- Recruiting
FISABIO
Alicante, 03658
Rocío Alfayate, PhD, 96591 ext. 9510, alfayate_roc@gva.es
- Recruiting
San Juan de Alicante Hospital
Sant Joan d'Alacant, Alicante, 03550
Maite López Garrigos, PhD, +34637848146, lopez_marter@gva.es
About this study
Official title: Study of the Adequacy of the Requests of Prostate-Specific Antigen (PSA), Factors Associated With the False Negative and Positive Results and the Impact on Patient's Health
Objectives:
The primary aim of this study is to evaluate the outcomes of the determination of PSA for the early detection of prostate cancer or in the presence of symptoms, in general practice in two health departments of the Valencian Community (Spain).
Read more
Specific objectives:
- To analyse the clinical and analytical factors associated with the presence of false positive and false negative results in PSA determinations in patients within the setting of opportunistic screening and in those with symptoms.
- To evaluate the patient's clinical outcome, diagnostic and/or clinical and/or therapeutic interventions implemented in each patient according to the PSA value and the patient's clinical variables during the two years of follow-up. Furthermore, the investigadors will study whether this management is appropriate to the recommendations of the European Society of Urology.
Read the detailed description
Sample size and recruitment procedure:
The investigators will select a cohort of patients with positive PSA results and a cohort of patients with negative results in each centre, to be followed for two years.
According to a review by the American Cancer Society, a value of PSA of 4 ng/ml had an estimated sensitivity of 21% to detect any type of prostate cancer and a specificity of 91%. The investigators estimate a prevalence of prostate cancer in this population not lower than 5% (given that the investigators include asymptomatic and symptomatic patients), with a 95% margin of error and 2% precision, the investigators will need to include 457 patients with a negative PSA result and 865 PSA-positive patients. Taking into account a 20% possible loss during follow-up, the investigators will increase to 572 patients with a negative PSA result (286 per centre) and 1,081 patients with a positive PSA result (541 per centre) who will be selected consecutively from among those included in the cross-sectional study until the investigators reach the proposed sample size. The investigators will use the initial randomized list (which included determinations during the first 6 months of 2018) to select patients who meet both negative and positive PSA criteria and if it is necessary, the investigators will continue to review analyses until the sample size is achieved.
Data collection procedure:
The investigators will follow both cohorts (positive and negative PSA results) for two years by reviewing their medical records (every 3 months for patients with a positive PSA result and annually for patients with a negative result). The following variables will be recorded: sociodemographic and clinical characteristics (patient who has the PSA determination as part of opportunistic screening or due to the presence of symptoms suggestive of disease), other comorbidities, toxic habits, previous history of cancer, family history, present pharmacological treatment and setting.
The investigators will evaluate the presence of false positive and negative results according to the latest recommendations of the European Association of Urology (specific objective 1).
The interventions performed after PSA determination and until the follow-up deadline, and their adaptation to the latest available recommendations (specific objective 2) will be evaluated separately by at least two investigators.
Data analysis plan The analysis will be performed using the Stata IC 15 program.
- Specific objective 1. The investigators will calculate the proportion of false positive and false negative results for the diagnosis of PCa and the associated variables. In the case of false positive tests, the investigators will also describe the time from a positive PSA result until PCa is ruled out using mean, standard deviation or median and interquartile ranges for the total population and relevant subgroups.
- Specific objective 2. The investigators will assess the probability of having a diagnostic, surgical or therapeutic intervention according to variables using risk ratio (statistical precision as for specific objective 1). If necessary, the investigators will use log-binomial regression estimating prevalence ratios. the investigators will also evaluate the agreement between the interventions performed and the available guidelines.
- Conditions
- Prostate-Specific Antigen /Blood
- Being tested
- Positive Prostate-Specific Antigen test result
- Keywords
- Prostatic Neoplasms, False Positive Reactions, False Negative Reactions, Disease Management
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Positive Prostate-Specific Antigen test resultDiagnostic test
Positive PSA test result as part of opportunistic screening or due to the presence of symptoms suggestive of disease.
| Study group | Role | What they receive |
|---|---|---|
| Positive PSA result | Men with a positive PSA test defined as:
* Serum total PSA concentration is over 10 ng/ml.
* Serum total PSA between 4 and 10 ng/ml if the value of the free PSA/total PSA fraction is under 25%, in at least in two determinations. Receives: Diagnostic Test: Positive Prostate-Specific Antigen test result | |
| Negative PSA result | Men with a negative PSA test defined as: * Serum total PSA concentration is under 10 ng/ml. * Serum total PSA between 4 and 10 ng/ml if the value of the free PSA/total PSA fraction is over 25%. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with a false-positive result in the determination of serum PSA levels.
False positive result of the PSA determination defined as follows:
If the PSA test is positive (meaning, serum total PSA level is over 10 ng/ml or serum total PSA level between 4 and 10 ng/ml if the value of the free PSA/total PSA fraction is under 25%, in at least in two determinations) and the result of digital rectal examination and/or subsequent biopsy is negative.
Measured: 2 years since PSA determination
Proportion of patients with a false-negative result in the determination of serum PSA levels
False negative result of the PSA determination defined as follows:
If the serum PSA value is negative (meaning, serum total PSA level is under 10 ng/ml or serum total PSA between 4 and 10 ng/ml if the value of the free PSA/total PSA fraction is over 25%) and the patient is diagnosed with prostate cancer in the subsequent follow-up.
Measured: 2 years since PSA determination
Frequency of patients with appropriate diagnostic interventions performed in those with a positive serum PSA value according to "EAU - ESTRO - ESUR - SIOG Guidelines on Prostate Cancer".
Appropriateness of diagnostic interventions is defined as strategies that satisfies or not satisfies EAU recommendations with regard to the following issues:
- Recommendations for clinical diagnosis of prostate cancer.
- Recommendations for repeat-biopsy imaging.
Measured: 2 years since PSA determination
Frequency of prostate cancer patients with an appropriate treatment protocol according to "EAU - ESTRO - ESUR - SIOG Guidelines on Prostate Cancer".
Appropriate treatment protocol is defined according to the EAU recommendations with regard to the number and type of therapeutic interventions carried out after prostate cancer diagnosis.
The following information will be considered:
- Surgical treatments.
- Radiotherapeutic treatments.
- Active therapeutic options outside surgery and radiotherapy.
Each patient will be classified as "Appropriate according to guideline", "more intensive than guideline" or "less intensive than guideline".
Measured: 2 years since PSA determination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2019
- Study start18 Jul 2018
- Primary completionJul 2020 (estimated)
- Study completionJul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Prostate-Specific Antigen /BloodStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,527 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universidad Miguel Hernandez de Elche
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Universitario San Juan de Alicante, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
- Responsible party
- Principal investigator, Blanca Juana Lumbreras Lacarra, Universidad Miguel Hernandez de Elche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03978299
- Sponsor's protocol ID
- PI17/01883.2
- Other IDs
- PI17/01883
- Status last verified
- Jun 2019
- First submitted
- 28 May 2019
- Last updated
- 11 Jun 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Wolf AM, Wender RC, Etzioni RB, Thompson IM, D'Amico AV, Volk RJ, Brooks DD, Dash C, Guessous I, Andrews K, DeSantis C, Smith RA; American Cancer Society Prostate Cancer Advisory Committee. American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin. 2010 Mar-Apr;60(2):70-98. doi: 10.3322/caac.20066. Epub 2010 Mar 3.
PubMed 20200110Chun FK, Epstein JI, Ficarra V, Freedland SJ, Montironi R, Montorsi F, Shariat SF, Schroder FH, Scattoni V. Optimizing performance and interpretation of prostate biopsy: a critical analysis of the literature. Eur Urol. 2010 Dec;58(6):851-64. doi: 10.1016/j.eururo.2010.08.041. Epub 2010 Sep 4.
PubMed 20884114Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, Fossati N, Gross T, Henry AM, Joniau S, Lam TB, Mason MD, Matveev VB, Moldovan PC, van den Bergh RCN, Van den Broeck T, van der Poel HG, van der Kwast TH, Rouviere O, Schoots IG, Wiegel T, Cornford P. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2017 Apr;71(4):618-629. doi: 10.1016/j.eururo.2016.08.003. Epub 2016 Aug 25.
PubMed 27568654Bernal-Soriano MC, Parker LA, Lopez-Garrigos M, Hernandez-Aguado I, Caballero-Romeu JP, Gomez-Perez L, Alfayate-Guerra R, Pastor-Valero M, Garcia N, Lumbreras B. Factors associated with false negative and false positive results of prostate-specific antigen (PSA) and the impact on patient health: Cohort study protocol. Medicine (Baltimore). 2019 Oct;98(40):e17451. doi: 10.1097/MD.0000000000017451.
PubMed 31577771
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Adequacy of the Requests of Prostate-Specific Antigen (PSA), Factors Associated With the False Negative and Positive Results and the Impact on Patient's Health
- ClinicalTrials.gov ID
- NCT03978299
- Acronym / sponsor ID
- PI17/01883.2
- Conditions
- Prostate-Specific Antigen /Blood
- Keywords
- Prostatic Neoplasms, False Positive Reactions, False Negative Reactions, Disease Management
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 2,527 participants (estimated)
- Lead sponsor
- Universidad Miguel Hernandez de ElcheUniversity, hospital or other
- Collaborators
- Hospital Universitario San Juan de Alicante, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
- Study start
- 18 Jul 2018 (actual)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Jul 2020 (estimated)
- First posted
- 7 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objectives:
The primary aim of this study is to evaluate the outcomes of the determination of PSA for the early detection of prostate cancer or in the presence of symptoms, in general practice in two health departments of the Valencian Community (Spain).
Specific objectives:
- To analyse the clinical and analytical factors associated with the presence of false positive and false negative results in PSA determinations in patients within the setting of opportunistic screening and in those with symptoms.
- To evaluate the patient's clinical outcome, diagnostic and/or clinical and/or therapeutic interventions implemented in each patient according to the PSA value and the patient's clinical variables during the two years of follow-up. Furthermore, the investigadors will study whether this management is appropriate to the recommendations of the European Society of Urology.
Detailed description
Sample size and recruitment procedure:
The investigators will select a cohort of patients with positive PSA results and a cohort of patients with negative results in each centre, to be followed for two years.
According to a review by the American Cancer Society, a value of PSA of 4 ng/ml had an estimated sensitivity of 21% to detect any type of prostate cancer and a specificity of 91%. The investigators estimate a prevalence of prostate cancer in this population not lower than 5% (given that the investigators include asymptomatic and symptomatic patients), with a 95% margin of error and 2% precision, the investigators will need to include 457 patients with a negative PSA result and 865 PSA-positive patients. Taking into account a 20% possible loss during follow-up, the investigators will increase to 572 patients with a negative PSA result (286 per centre) and 1,081 patients with a positive PSA result (541 per centre) who will be selected consecutively from among those included in the cross-sectional study until the investigators reach the proposed sample size. The investigators will use the initial randomized list (which included determinations during the first 6 months of 2018) to select patients who meet both negative and positive PSA criteria and if it is necessary, the investigators will continue to review analyses until the sample size is achieved.
Data collection procedure:
The investigators will follow both cohorts (positive and negative PSA results) for two years by reviewing their medical records (every 3 months for patients with a positive PSA result and annually for patients with a negative result). The following variables will be recorded: sociodemographic and clinical characteristics (patient who has the PSA determination as part of opportunistic screening or due to the presence of symptoms suggestive of disease), other comorbidities, toxic habits, previous history of cancer, family history, present pharmacological treatment and setting.
The investigators will evaluate the presence of false positive and negative results according to the latest recommendations of the European Association of Urology (specific objective 1).
The interventions performed after PSA determination and until the follow-up deadline, and their adaptation to the latest available recommendations (specific objective 2) will be evaluated separately by at least two investigators.
Data analysis plan The analysis will be performed using the Stata IC 15 program.
- Specific objective 1. The investigators will calculate the proportion of false positive and false negative results for the diagnosis of PCa and the associated variables. In the case of false positive tests, the investigators will also describe the time from a positive PSA result until PCa is ruled out using mean, standard deviation or median and interquartile ranges for the total population and relevant subgroups.
- Specific objective 2. The investigators will assess the probability of having a diagnostic, surgical or therapeutic intervention according to variables using risk ratio (statistical precision as for specific objective 1). If necessary, the investigators will use log-binomial regression estimating prevalence ratios. the investigators will also evaluate the agreement between the interventions performed and the available guidelines.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Positive PSA result | – | Diagnostic Test: Positive Prostate-Specific Antigen test resultMen with a positive PSA test defined as: * Serum total PSA concentration is over 10 ng/ml. * Serum total PSA between 4 and 10 ng/ml if the value of the free PSA/total PSA fraction is under 25%, in at least in two determinations. |
| Negative PSA result | – | –Men with a negative PSA test defined as: * Serum total PSA concentration is under 10 ng/ml. * Serum total PSA between 4 and 10 ng/ml if the value of the free PSA/total PSA fraction is over 25%. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Men over 18 from the Health Department 17 and 19, in the Valencian Community (these include General University Hospital of Sant Joan d'Alacant and General University Hospital of Alicante, respectively). These are referral hospitals for all individuals living in their catchment areas and belong to the National Health Care System (the majority of the population in Spain uses the National Health System (NHS) as the main medical service (the publicly funded insurance scheme covers 98.5% of the Spanish population). The investigators have not established maximum age limit.
Key inclusion criteria (1 listed)
- Patients with a PSA determination result in a routine health examination from the Health Department 17 and 19, in the Valencian Community (Spain)
Key exclusion criteria (2 listed)
- Patients who have been previously diagnosed with prostate cancer.
- Patients who are being followed for previous high PSA values.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Positive Prostate-Specific Antigen test resultPositive PSA test result as part of opportunistic screening or due to the presence of symptoms suggestive of disease. | Diagnostic test | Positive PSA result |
Primary outcome
Proportion of patients with a false-positive result in the determination of serum PSA levels.
Time frame: 2 years since PSA determination
False positive result of the PSA determination defined as follows: If the PSA test is positive (meaning, serum total PSA level is over 10 ng/ml or serum total PSA level between 4 and 10 ng/ml if the value of the free PSA/total PSA fraction is under 25%, in at least in two determinations) and the result of digital rectal examination and/or subsequent biopsy is negative.
Proportion of patients with a false-negative result in the determination of serum PSA levels
Time frame: 2 years since PSA determination
False negative result of the PSA determination defined as follows: If the serum PSA value is negative (meaning, serum total PSA level is under 10 ng/ml or serum total PSA between 4 and 10 ng/ml if the value of the free PSA/total PSA fraction is over 25%) and the patient is diagnosed with prostate cancer in the subsequent follow-up.
Frequency of patients with appropriate diagnostic interventions performed in those with a positive serum PSA value according to "EAU - ESTRO - ESUR - SIOG Guidelines on Prostate Cancer".
Time frame: 2 years since PSA determination
Appropriateness of diagnostic interventions is defined as strategies that satisfies or not satisfies EAU recommendations with regard to the following issues: * Recommendations for clinical diagnosis of prostate cancer. * Recommendations for repeat-biopsy imaging.
Frequency of prostate cancer patients with an appropriate treatment protocol according to "EAU - ESTRO - ESUR - SIOG Guidelines on Prostate Cancer".
Time frame: 2 years since PSA determination
Appropriate treatment protocol is defined according to the EAU recommendations with regard to the number and type of therapeutic interventions carried out after prostate cancer diagnosis. The following information will be considered: * Surgical treatments. * Radiotherapeutic treatments. * Active therapeutic options outside surgery and radiotherapy. Each patient will be classified as "Appropriate according to guideline", "more intensive than guideline" or "less intensive than guideline".
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2019.
- Background: PubMed 20200110Wolf AM, Wender RC, Etzioni RB, Thompson IM, D'Amico AV, Volk RJ, Brooks DD, Dash C, Guessous I, Andrews K, DeSantis C, Smith RA; American Cancer Society Prostate Cancer Advisory Committee. American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin. 2010 Mar-Apr;60(2):70-98. doi: 10.3322/caac.20066. Epub 2010 Mar 3.
- Background: PubMed 20884114Chun FK, Epstein JI, Ficarra V, Freedland SJ, Montironi R, Montorsi F, Shariat SF, Schroder FH, Scattoni V. Optimizing performance and interpretation of prostate biopsy: a critical analysis of the literature. Eur Urol. 2010 Dec;58(6):851-64. doi: 10.1016/j.eururo.2010.08.041. Epub 2010 Sep 4.
- Background: PubMed 27568654Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, Fossati N, Gross T, Henry AM, Joniau S, Lam TB, Mason MD, Matveev VB, Moldovan PC, van den Bergh RCN, Van den Broeck T, van der Poel HG, van der Kwast TH, Rouviere O, Schoots IG, Wiegel T, Cornford P. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2017 Apr;71(4):618-629. doi: 10.1016/j.eururo.2016.08.003. Epub 2016 Aug 25.
- Derived from this study: PubMed 31577771Bernal-Soriano MC, Parker LA, Lopez-Garrigos M, Hernandez-Aguado I, Caballero-Romeu JP, Gomez-Perez L, Alfayate-Guerra R, Pastor-Valero M, Garcia N, Lumbreras B. Factors associated with false negative and false positive results of prostate-specific antigen (PSA) and the impact on patient health: Cohort study protocol. Medicine (Baltimore). 2019 Oct;98(40):e17451. doi: 10.1097/MD.0000000000017451.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prostate-Specific Antigen /Blood, run by Universidad Miguel Hernandez de Elche at 2 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Blanca J Lumbreras, PhD (96591 ext. 9510, blumbreras@umh.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with a false-positive result in the determination of serum PSA levels. (time frame: 2 years since PSA determination). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03978299, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2019.