Revolutionary Blood Test Could Transform Prostate Cancer Screening and Monitoring

Utility of the PROSTest, a Novel Blood‐Based Molecular Assay, Versus PSA for Prostate Cancer Stratification and Detection of Disease

PROSTest Shows 97% Accuracy in Detection—But Questions Remain About Long-Term Surveillance Applications

Men navigating prostate cancer screening and treatment decisions may soon have access to a more accurate blood test that could reduce unnecessary biopsies while catching cancer more reliably than PSA. However, while the technology shows impressive initial results, critical questions remain about its use for active surveillance and monitoring after treatment.

A prospective study of 105 men in Poland, published recently in The Prostate, found that a novel blood test called PROSTest dramatically outperformed standard PSA testing in detecting prostate cancer. The results were striking: 97% sensitivity, 96% specificity, and an area under the curve (AUROC) of 0.99 compared to PSA's 0.61.

"While PSA is useful for identifying men at risk, its low specificity leads to unnecessary biopsies particularly of clinically nonsignificant disease," the researchers noted. This limitation has contributed to reduced PSA screening in recent years, which has unfortunately led to increased late-stage diagnoses and mortality.

How PROSTest Works

Unlike PSA, which measures a single protein in the blood, PROSTest analyzes the expression levels of 27 different genes associated with tumor biology. The test uses advanced machine learning algorithms to generate a risk score from 0 to 100, with scores of 50 or higher indicating increased risk for prostate cancer.

The blood sample is collected in special RNA stabilization tubes, and the analysis uses PCR (polymerase chain reaction) technology to measure gene expression levels. These genes capture molecular signatures that PSA testing cannot detect.

"Unlike current tissue-based panels such as Prolaris or OncoTypeDX, which do not capture these molecular targets, PROSTest analyzes 27 genes associated with tumor pathobiology," the researchers explained.

Initial Detection: Impressive Results

The Polish study enrolled men over age 55 with PSA levels above 2 ng/mL who were experiencing symptoms suggestive of prostate cancer. All participants underwent MRI-ultrasound fusion biopsy, the gold standard for diagnosis.

Study population breakdown:

• 65 men (62%) were diagnosed with prostate cancer
• 27 had Gleason Grade 1 disease (lower risk)
• 38 had Gleason Grade 2-5 disease (clinically significant cancer)
• 40 had benign prostatic hyperplasia (BPH) or other non-cancerous conditions
• Median age: 68 years
• Median PSA: 8.2 ng/mL

PROSTest performance:

• Correctly identified 63 of 65 cancer cases (97% sensitivity)
• Correctly identified 38 of 40 men without cancer (96% specificity)
• Only 2 men with cancer had negative results (both lower-grade disease)
• Only 2 men without cancer had false positive results

Reducing Unnecessary Biopsies

One of the most significant potential benefits involves reducing unnecessary procedures. In this study:

• Using a PSA cutoff of 10 ng/mL would have avoided 64 biopsies (61%) but missed 21 cases of clinically significant cancer
• Using PROSTest with its standard cutoff of 50 could have avoided 40 biopsies (38%) while detecting all clinically significant cancers
• The test also identified 25 of 27 (93%) cases of lower-grade disease

This represents a substantial improvement in the risk-benefit balance of prostate cancer screening.

The Active Surveillance Question: Promise and Limitations

For the many men diagnosed with low-grade prostate cancer who choose active surveillance over immediate treatment, PROSTest's potential role remains uncertain despite encouraging signals.

What the Data Shows

The Polish study found that PROSTest scores were significantly higher in men with clinically significant cancer (GG2-5), with average scores of 92 ± 3.8, compared to those with GG1 disease (87 ± 3.0) and benign conditions (9.4 ± 16). The overall difference was statistically significant (p < 0.0001).

However, the direct comparison between GG1 and GG2-5 showed only a trend (p = 0.116), suggesting the test may not yet reliably distinguish low-grade from high-grade disease in individual patients.

PSA levels, by contrast, showed no significant difference across groups: GG2-5 had median PSA of 8.6 ng/mL, GG1 disease 9.8 ng/mL, and other prostatic conditions 6.8 ng/mL (p = 0.159).

The Critical Limitation: Score Overlap

A closer look at the data reveals an important challenge for active surveillance applications:

• Some GG1 patients had PROSTest scores as low as 71
• Others had scores in the 90s, similar to high-grade disease
• This overlap means the test cannot yet definitively categorize individual patients

The researchers acknowledged this concern: "Another consideration is the overlap between GG1 and GG2-5. Biopsy-based grading has inherent limitations, as a proportion of cases may be up- or downgraded upon review of surgical pathology specimens."

What Would Make PROSTest Useful for Active Surveillance?

For active surveillance monitoring, an ideal biomarker test needs to:

1. Reliably distinguish indolent from aggressive disease at diagnosis
2. Detect progression from low-grade to high-grade disease over time
3. Maintain high negative predictive value to reassure patients that continued observation is safe
4. Show stability over time in men with truly indolent disease

The current study provides preliminary evidence for the first criterion but doesn't address the others, as it was a single-timepoint analysis without longitudinal follow-up.

Post-Treatment Monitoring: Limited But Intriguing Evidence

For men who have undergone surgery or radiation therapy, the question of whether PROSTest can detect recurrence or predict outcomes remains largely unanswered.

Evidence from Previous Studies

A 2025 American validation study by Rahbar et al. provides the best available evidence for post-treatment applications. That study found that PROSTest scores correlated with PSA doubling time (PSADT) after treatment:

• Lower PROSTest scores (< 90) were associated with longer PSA doubling times
• Higher scores (90-100) were associated with shorter doubling times and more aggressive disease behavior

This is clinically significant because PSA doubling time is an important marker of disease aggressiveness after treatment. A shorter doubling time suggests more aggressive cancer behavior and potential need for additional treatment.

A 2024 study by Rosin et al. in Caribbean populations evaluated PROSTest "for Prostate Cancer Detection and Follow-Up," though detailed results on the longitudinal monitoring component have not been fully published.

Critical Unanswered Questions

The existing studies leave several important questions for post-treatment patients:

About Biochemical Recurrence:

• Can PROSTest detect recurrence earlier than PSA alone?
• What score threshold indicates recurrence?
• How do scores change from pre-treatment to post-treatment to recurrence?

About Treatment Response:

• Do scores decrease after successful surgery or radiation?
• How quickly do scores change?
• Can the test distinguish residual benign tissue from persistent cancer?

About Predicting Outcomes:

• Can pre-treatment scores predict surgical success?
• Do scores predict radiation therapy response?
• Can the test identify patients at high risk for recurrence?

About Testing Frequency:

• How often should the test be performed during surveillance?
• Is there value in serial testing versus single measurements?
• Do scores fluctuate with normal biological variations?

Comparison to Existing Tests

Blood-Based PSA Refinement Tests

Prostate Health Index (PHI):

• FDA-approved for men with PSA 2-10 ng/mL
• Measures three PSA subtypes
• Performance varies across ethnic groups and geographic regions

4Kscore:

• Combines four biomarkers with clinical factors
• Generates 0-100% risk score
• Also shows demographic variability

Both tests refine PSA interpretation but still rely fundamentally on PSA measurements.

Urine-Based Molecular Tests

SelectMDx:

• Measures mRNA levels of HOXC6 and DLX1
• Currently being optimized for negative predictive value
• Requires post-DRE urine sample

PCA3 Test:

• Measures PCA3 and PSA mRNA in urine after DRE
• Recommended by EAU and NCCN for repeat biopsy decisions
• Not currently used for initial risk stratification

ExoDx Prostate (IntelliScore):

• Analyzes ERG, PCA3, and SPDEF from urinary exosomes
• High sensitivity (> 90%)
• Many men with low scores defer biopsy for years

Tissue-Based Genomic Tests

Prolaris (Cell Cycle Progression Score):

• Measures cell cycle gene expression in tumor tissue
• Predicts progression risk in active surveillance patients
• Predicts biochemical recurrence after treatment
• Requires tumor tissue from biopsy or surgery

Oncotype DX Genomic Prostate Score:

• Analyzes 12 cancer genes plus 5 reference genes
• Predicts likelihood of high-grade disease
• Helps with active surveillance decisions
• Also requires tumor tissue

Decipher Genomic Classifier:

• 22-gene test on prostatectomy specimens
• Predicts risk of metastasis
• Guides adjuvant therapy decisions
• Requires surgical tissue

PROSTest's Potential Advantages

1. Non-invasive: Simple blood test versus tissue requirement
2. Repeatable: Can be performed multiple times without additional biopsies
3. Real-time monitoring: Reflects current disease state in the body
4. Broader applicability: Potentially useful before biopsy, during active surveillance, and after treatment
5. Superior initial detection: Significantly outperforms PSA in head-to-head comparison

Potential Limitations

1. Less tumor-specific: Tissue tests directly analyze cancer cells
2. Unknown longitudinal stability: Do blood-based scores fluctuate with normal variations?
3. Limited validation: Tissue tests have years of clinical validation data
4. Score overlap: Cannot yet definitively distinguish GG1 from GG2-5 in individual patients
5. No post-treatment validation: Insufficient data for surveillance after surgery or radiation

Clinical Scenarios: Where PROSTest Might Help

Scenario 1: Initial Screening Decision

Patient: 62-year-old man with PSA of 5.8 ng/mL, normal DRE, family history of prostate cancer

Current challenge: PSA alone cannot distinguish cancer from BPH; biopsy carries risks of infection and over-detection of insignificant disease

Potential PROSTest role:

• Score < 50: High confidence to defer biopsy and continue monitoring
• Score > 50: Proceed with MRI and/or biopsy
• Based on 96% specificity, could avoid 38% of unnecessary biopsies

Evidence level: Strong—this is the validated use case from the Polish study

Scenario 2: Active Surveillance Decision

Patient: 58-year-old man newly diagnosed with Gleason 6 (GG1) disease via biopsy; MRI shows small focal lesion; must decide between immediate treatment and active surveillance

Current challenge: Uncertainty about whether biopsy captured true disease grade; concern about harboring hidden high-grade cancer

Potential PROSTest role:

• Low score (< 90): Additional reassurance for choosing active surveillance
• High score (> 90): Suggests possible hidden high-grade disease; consider repeat biopsy or treatment

Evidence level: Weak—preliminary data shows score differences between grades, but overlap limits individual patient decision-making

Current recommendation: Should not replace standard active surveillance eligibility criteria

Scenario 3: Active Surveillance Monitoring

Patient: 60-year-old man on active surveillance for GG1 disease for 2 years; PSA stable; due for repeat biopsy

Current challenge: Repeat biopsies are uncomfortable, carry infection risk, and may still miss progression; need better way to monitor between biopsies

Potential PROSTest role:

• Serial measurements every 6-12 months
• Stable low scores might provide reassurance between biopsies
• Rising scores could trigger earlier intervention or MRI

Evidence level: None—no published longitudinal data on score changes during active surveillance

Current recommendation: Cannot replace standard active surveillance protocols; investigational only

Scenario 4: Post-Prostatectomy Monitoring

Patient: 65-year-old man, 6 months post-radical prostatectomy for GG3 disease; PSA undetectable; concerned about recurrence risk

Current challenge: PSA is the only monitoring tool, but by the time PSA becomes detectable, cancer may be well-established

Potential PROSTest role:

• Baseline post-surgery score might predict recurrence risk
• Rising scores could detect recurrence earlier than PSA
• Could guide timing of salvage radiation

Evidence level: Very limited—one study showed correlation with PSA doubling time, but no validation for recurrence detection

Current recommendation: Should not replace PSA monitoring; investigational only

Scenario 5: Post-Radiation Monitoring

Patient: 70-year-old man, 18 months post-radiation therapy for GG2 disease; PSA nadir was 0.8 ng/mL, now rising slowly to 1.4 ng/mL

Current challenge: PSA doesn't reach zero after radiation; "Phoenix criteria" (PSA rise of 2 ng/mL above nadir) may detect recurrence too late

Potential PROSTest role:

• Might help distinguish persistent benign tissue from active cancer
• Could provide information when PSA behavior is ambiguous
• May predict late recurrences earlier

Evidence level: None—no published data on PROSTest in radiation-treated patients

Current recommendation: Should not replace standard post-radiation PSA monitoring

What Research Is Still Needed

For Active Surveillance Applications

Study design requirements:

1. Longitudinal cohorts with baseline and serial measurements over 5-10 years
2. Grade reclassification events as primary outcome (upgrading from GG1 to ≥GG2)
3. Comparison to existing protocols (PRIAS, Johns Hopkins, UCSF criteria)
4. Integration with MRI to assess added value beyond imaging
5. Cost-effectiveness analysis of adding PROSTest to active surveillance protocols

Key questions to answer:

• What score change over time indicates disease progression?
• Can stable scores safely extend intervals between biopsies?
• Does PROSTest add value beyond PSA density and MRI findings?
• What is the test-retest reliability over weeks to months?

For Post-Treatment Monitoring

Study design requirements:

1. Paired samples pre- and post-treatment from same patients
2. Long-term follow-up with biochemical recurrence as outcome
3. Treatment-specific cohorts (surgery vs. radiation vs. ADT)
4. Comparison to PSA kinetics (doubling time, velocity)
5. Metastasis and survival outcomes in extended follow-up

Key questions to answer:

• What are normal post-treatment score ranges?
• How quickly do scores change after successful treatment?
• What score threshold indicates recurrence?
• Can the test guide salvage therapy decisions?

Study Limitations and Caveats

The researchers were forthright about their study's limitations:

Sample size: With only 105 participants, this represents preliminary evidence. The authors emphasized that "larger prospective studies are needed to validate these findings and further define its clinical utility."

Geographic limitation: All participants were from Poland. Performance may vary in other populations, though previous studies have shown efficacy in American and Caribbean populations, including men of African genetic heritage.

Single timepoint: The study captured one measurement per patient, providing no information about score stability over time or ability to detect progression.

Biopsy sampling limitations: Some cancers classified as Gleason Grade 1 may be upgraded after surgery, and some Grade 2-5 cancers may be downgraded, which affects the accuracy of comparing PROSTest scores to biopsy grades.

No MRI comparison: The study didn't evaluate how PROSTest performs relative to multiparametric MRI, now considered standard of care in many centers.

Selection bias: All patients had symptoms suggestive of prostate cancer and PSA > 2 ng/mL, so results may not apply to asymptomatic screening populations.

Current Clinical Recommendations

What PROSTest Should Be Used For (Once Validated):

• Initial detection of prostate cancer in symptomatic men with elevated PSA
• Risk stratification to reduce unnecessary biopsies
• Possibly distinguishing clinically significant from insignificant disease

What PROSTest Should NOT Currently Be Used For:

• Making active surveillance eligibility decisions
• Monitoring disease progression during active surveillance
• Replacing PSA monitoring after surgery or radiation
• Guiding salvage therapy timing
• Making treatment versus surveillance decisions

The test remains investigational for all surveillance and post-treatment applications.

Questions for Your Healthcare Team

If You're Considering Screening:

1. Am I a candidate for prostate cancer screening based on my age, family history, and risk factors?
2. Beyond PSA and DRE, what other screening tools might help assess my risk?
3. If my PSA is elevated, what's the next step—immediate biopsy, MRI, or additional blood tests?
4. Are there clinical trials for newer screening technologies available at your center?

If You're on Active Surveillance:

1. What criteria determine if my cancer is progressing?
2. How often will I need PSA testing, DRE, MRI, and repeat biopsies?
3. Are there biomarker tests beyond PSA that might help monitor my disease?
4. What would trigger a recommendation to move from surveillance to treatment?

If You're Post-Treatment:

1. What PSA pattern would concern you for recurrence?
2. How often will I need PSA monitoring, and for how long?
3. Are there blood tests beyond PSA that might detect recurrence earlier?
4. At what point would you recommend additional imaging or salvage treatment?

About Emerging Technologies:

1. How do you evaluate new diagnostic tests before incorporating them into practice?
2. Are there clinical trials at your institution for novel biomarkers?
3. Would you recommend additional testing beyond standard protocols for my situation?

The Path Forward

PROSTest represents a significant advance in prostate cancer detection, with impressive sensitivity and specificity that substantially exceed PSA testing. The technology's use of machine learning applied to a 27-gene panel offers a sophisticated approach that captures molecular signatures missed by conventional biomarkers.

For initial detection and biopsy decisions, the evidence is compelling. The test could meaningfully reduce unnecessary biopsies while maintaining excellent cancer detection rates—a long-sought goal in prostate cancer screening.

For active surveillance and post-treatment monitoring, the picture is less clear. While preliminary signals are encouraging—particularly the correlation between higher scores and more aggressive disease—critical validation studies have not yet been completed. The overlap in scores between low-grade and high-grade disease, combined with the lack of longitudinal data, means the test cannot yet replace established surveillance protocols.

The research community needs to prioritize:

• Large, multi-center longitudinal studies tracking patients over years
• Validation across diverse populations and treatment scenarios
• Head-to-head comparisons with tissue-based genomic tests and MRI
• Economic analyses assessing cost-effectiveness
• Regulatory pathways for specific clinical indications

For patients, PROSTest represents hope for more personalized, less invasive prostate cancer management. However, that hope must be tempered with realistic acknowledgment of what is proven versus what remains theoretical.

Men currently facing screening decisions should discuss with their healthcare providers whether newer biomarker tests might be appropriate for their situation. Those on active surveillance or in post-treatment monitoring should continue with established protocols while staying informed about emerging technologies that may eventually enhance their care.

As one patient advocate put it: "We don't need perfection—we need progress." PROSTest appears to represent genuine progress in prostate cancer detection. Whether it will also transform surveillance and monitoring practices remains an open and important question that only rigorous research can answer.

---

Sources

1. Kidd, M., Rempega, G., Kepinski, M., Slomian, S., Mlynarek, K., & Halim, A. B. (2025). Utility of the PROSTest, a Novel Blood-Based Molecular Assay, Versus PSA for Prostate Cancer Stratification and Detection of Disease. The Prostate, 1-7. https://doi.org/10.1002/pros.70086

2. Rahbar, K., Kidd, M., Prasad, V., Rosin, R. D., Drozdov, I., & Halim, A. (2025). Clinical Sensitivity and Specificity of the PROSTest in an American Cohort. Prostate, 85(6), 558-566.

3. Modlin, I. M., Kidd, M., Drozdov, I. A., et al. (2024). Development of a Multigenomic Liquid Biopsy (PROSTest) for Prostate Cancer in Whole Blood. Prostate, 84(9), 850-865.

4. Rosin, R. D., Haynes, A., Kidd, M., Drozdov, I., Modlin, I., & Halim, A. (2024). Evaluation of a Multigenomic Liquid Biopsy (PROSTest) for Prostate Cancer Detection and Follow-Up in a Caribbean Population. Cancer Epidemiology, 92, 102642.

5. Rawla, P. (2019). Epidemiology of Prostate Cancer. World Journal of Oncology, 10(2), 63-89. https://doi.org/10.14740/wjon1191

6. Cornford, P., van den Bergh, R. C. N., Briers, E., et al. (2024). EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment With Curative Intent. European Urology, 86(2), 148-163. https://doi.org/10.1016/j.eururo.2024.03.027

7. Grossman, D. C., Curry, S. J., Owens, D. K., et al. (2018). Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement. Journal of the American Medical Association, 319(18), 1901-1913. https://doi.org/10.1001/jama.2018.3710

8. American Cancer Society. Prostate Cancer Early Detection Guidelines. https://www.cancer.org/content/dam/CRC/PDF/Public/8795.00.pdf

9. Cooperberg, M. R., & Carroll, P. R. (2015). Trends in Management for Patients With Localized Prostate Cancer, 1990-2013. JAMA, 314(1), 80-82. https://doi.org/10.1001/jama.2015.6036

10. Epstein, J. I., Zelefsky, M. J., Sjoberg, D. D., et al. (2016). A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason Score. European Urology, 69(3), 428-435. https://doi.org/10.1016/j.eururo.2015.06.046

11. National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Prostate Cancer. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

12. Catalona, W. J., Partin, A. W., Sanda, M. G., et al. (2011). A Multicenter Study of [-2]Pro-Prostate Specific Antigen Combined With Prostate Specific Antigen and Free Prostate Specific Antigen for Prostate Cancer Detection in the 2.0 to 10.0 ng/ml Prostate Specific Antigen Range. Journal of Urology, 185(5), 1650-1655. https://doi.org/10.1016/j.juro.2010.12.032

13. Van Neste, L., Hendriks, R. J., Dijkstra, S., et al. (2016). Detection of High-grade Prostate Cancer Using a Urinary Molecular Biomarker-Based Risk Score. European Urology, 70(5), 740-748. https://doi.org/10.1016/j.eururo.2016.04.012

14. McKiernan, J., Donovan, M. J., O'Neill, V., et al. (2016). A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy. JAMA Oncology, 2(7), 882-889. https://doi.org/10.1001/jamaoncol.2016.0097