Capillary Blood for Prostate-specific Antigen Testing: The PSA-CAP Study

Abstract

Risk-adapted prostate cancer (PC) screening is currently based on a combination of prostate-specific antigen (PSA) testing, risk assessment, and magnetic resonance imaging (MRI). Classical venous blood sampling is usually performed by health care professionals, which may reduce participation in future population-based screening programmes due to limited resources. The PSA-CAP study (NCT06626386) evaluated the feasibility of using capillary blood from fingertip sampling compared with venous blood for PSA determination, in order to facilitate access for PSA testing. This prospective study analysed 196 men aged 40–75 yr. PSA levels were measured from both capillary and venous blood using the same analytical method. The stability of samples stored at room temperature was assessed over a week. Discomfort associated with both collection methods was evaluated using a numerical pain scale. No significant differences were found between capillary and venous PSA measurements. Samples remained stable up to 7 d without immediate centrifugation. Pain scores for capillary (1.52/10) and venous (1.61/10) collections were generally low and not significantly different (p = 0.27). Four cases had insufficient capillary blood for an analysis, and two outliers were resolved upon retesting. Capillary blood sampling is a viable alternative to venous puncture for PSA measurement, offering the same level of accuracy and stability with no difference in discomfort. This approach could enhance participation rates in future PC screening programmes.

Patient summary

We studied an alternative method of blood collection to measure prostate-specific antigen level, a key test for prostate cancer risk, using fingertip sampling instead of venous blood. The results were comparable with and as stable as those from venous blood collection, with similar comfort levels. This technique may simplify future prostate cancer screening programmes and could lead to a higher acceptance rate.

Population-based screening requires high participation rates, which are particularly critical for risk-adapted prostate cancer (PC) screening. Acceptance rates for PC screening invitations are generally low [1,2]. Modern diagnostic pathways currently include blood-based biomarkers such as prostate-specific antigen (PSA) and imaging modalities such as magnetic resonance imaging (MRI) [3,4]. Within the PRAISE-U project, an organised PC screening approach incorporating MRI and PSA testing is being evaluated across Europe, with Ireland piloting a home-based PSA self-test [5].

Classical venous blood sampling in health care settings limits accessibility due to resource constraints. Lowering the threshold for sampling, such as using capillary blood, may improve acceptance. As demonstrated in previous studies, World Health Organization (WHO)-calibrated venous PSA tests show variability of over 20% [6]. A study by Van den Brink et al [7] suggests that capillary blood can also be used effectively for PSA measurement in the context of self-sampling. In contrast, point-of-care tests have failed to gain widespread acceptance and currently do not meet the REASSURE criteria due to insufficient measurement precision [8,9].

This study investigates capillary blood sampling as an alternative for laboratory-based PSA testing using WHO-calibrated assays, eliminating the need for venous puncture. The prospective PSA-CAP study (NCT06626386) compares PSA values from venous and capillary samples, aiming to determine the comparability of capillary blood and venous PSA testing and assess storage durations for future screening applications.

This study evaluated 200 men (aged 40–75 yr) undergoing routine clinical PSA measurement, approved by the local ethics committee (no. 2024-2832).

Capillary blood (six drops) was collected from the fingertip using 500 µl Microvette Serum Gel tubes (Sarstedt, Germany; order no. 20.1344). Venous blood was collected using 5 ml BD Vacutainer SST II Advance Plus tubes (BD, UK; Ref 366566) by physicians and medical assistants. Samples were sent to the central laboratory, where centrifugation was performed upon arrival at 4000 rpm for 7 min for both tube types. Capillary serum of 50 μl was diluted with 150 µl of Diluent Universal (Roche Diagnostics GmbH, Mannheim, Germany).

PSA determination for capillary and venous samples was conducted using the Elecsys total PSA assay, an electrochemiluminescence immunoassay applied on the e801 module of the cobas 8000 analyser system (Roche Diagnostics GmbH). Calibration was standardised against the Stanford Reference Standard/WHO 96/670. Samples above the measurable range (0.006–100 ng/ml) were diluted automatically (factor 1:50). PSA measurements were conducted on the day of collection (T0).

To assess stability, three additional venous samples were stored at room temperature without centrifugation and transferred after 24 h (T1), 72 h (T2), and 1 wk (T3). These were centrifuged and analysed for PSA measurement.

The laboratory adhered to quality control requirements as per the German Medical Association’s guideline on quality assurance in medical laboratory examinations—Rili-BAEK [10]. Internal quality control for venous PSA used PreciControl Tumor Marker (Roche Diagnostics GmbH), with a permissible deviation of ±15.5%. External quality assessments allowed ±25% deviation.

Discomfort from venous or capillary blood collection was assessed using the numerical rating scale (NRS). Agreement between capillary and venous PSA values was evaluated using the Bland-Altman analysis, with 95% limits of agreement (LOAs) calculated from log-transformed PSA values, back-transformed to ratios.

A sample size of 200 provided a 95% confidence interval for an LOA of ±0.24s, where s is the standard deviation of differences between methods.

Between May and October 2024, 200 men (median age 61 yr, range 40–75 yr) were recruited. Four cases had insufficient capillary blood for PSA measurement, leaving 196 men for a statistical analysis. Differences in PSA values between venous and capillary blood were evaluated for all 196 samples.

Venous PSA values were stratified into three groups: PSA <1.5 ng/ml (n = 79), PSA 1.5–2.99 ng/ml (n = 26), and PSA ≥3 ng/ml (n = 91), following the PROBASE trial categories [2].

Using the Bland-Altman method, venous and capillary PSA measurements at T0 demonstrated no significant differences, indicating good agreement between the two methods. The estimated bias (venous vs capillary) was 0.953, with LOAs of 0.646–1.406 and a clinically acceptable coefficient of variation of 21.94% (see Fig. 1).

Fig. 1.

Agreement between venous and capillary PSA measurements in samples. PSA = prostate-specific antigen.

Results for PSA groups were as follows: PSA <1.5 ng/ml: bias 0.919, LOA 0.518–1.631; PSA 1.5–2.99 ng/ml: bias 0.960, LOA 0.713–1.292; and PSA ≥3 ng/ml: bias 0.982, LOA 0.888–1.086 (Fig. 1 and Supplementary Fig. 1A–C).

Samples with PSA differences within 20% of venous values were deemed acceptable based on variability in WHO-calibrated assays [6]. Two outliers were identified: (1) capillary 1.3 ng/ml versus venous 0.49 ng/ml and (2) capillary 3.2 ng/ml versus venous 1.54 ng/ml.

Stability testing showed no significant differences in venous PSA values across the time points (T0, T1, T2, and T3). Median PSA values at T0 (PSA <1.5 ng/ml: 0.79 ng/ml; PSA 1.5–2.99 ng/ml: 2.19 ng/ml; and PSA ≥3 ng/ml: 6.58 ng/ml) were consistent with those at T1, T2, and T3 (T0 vs T1, p = 0.99; T0 vs T2, p = 0.85; and T0 vs T3, p = 0.55, Mann–Whitney U test; Fig. 2 and Supplementary Fig. 2).

Fig. 2.

Venous PSA values across sampling time points T0, T1, T2, and T3. PSA = prostate-specific antigen; T0 = the day of collection; T1 = 24 h after collection; T2 = 72 h after collection; T3 = 1 wk after collection.

Pain scores (NRS) showed no significant difference between capillary (median 1.52, interquartile range [IQR] 0–2) and venous (median 1.61, IQR 0–2) blood collection (p = 0.96, Wilcoxon signed rank test).

Capillary and venous PSA values were comparable when appropriate sampling procedures were employed, with samples remaining stable at room temperature for up to 7 d without immediate centrifugation. Capillary blood collection from the fingertip was not associated with greater discomfort than venous sampling. These results suggest that capillary blood sampling is a feasible, accessible, and cost-effective approach for PC screening, suitable for self-testing or administration by non–health care professionals.

This study utilised a single measurement platform in a centralised laboratory. Further validation involving other platforms, methodologies, and laboratories is necessary to support broader application. Notably, PSA measurement in capillary blood has the potential to integrate WHO-calibrated assays with decentralised, online data management, facilitating nationwide screening programmes outside the traditional health care framework, while PSA testing for diagnostic purposes further on relies on regular assessment of venous serum or plasma in certified clinical laboratories.



Author contributions: Rouvier Al-Monajjed had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.



Study concept and design: Al-Monajjed, Albers, Boege, Wallisch, Benner, Hermsen.

Acquisition of data: Al-Monajjed, Wallisch, Lakes, Radtke, Hermsen, Londhe.

Analysis and interpretation of data: Al-Monajjed, Becker, Benner, Albers.

Drafting of the manuscript: Al-Monajjed, Albers, Becker, Wallisch.

Critical revision of the manuscript for important intellectual content: Albers, Boege, Al-Monajjed, Krilaviciute, Benner, Radtke, Holdenrieder, Becker, Seibold, Hermsen.

Statistical analysis: Benner, Saadati, Al-Monajjed, Wallisch.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: Al-Monajjed, Albers, Boege, Holdenrieder, Benner, Hermsen.

Other: None.



Financial disclosures: Rouvier Al-Monajjed certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.



Funding/Support and role of the sponsor: None.

Associate Editor: Roderick van den Bergh

Appendix A. Supplementary data

The following are the Supplementary data to this article: