miRNA Panel for PCa Diagnosis

This is a single-center, prospective diagnostic accuracy trial conducted at Renji Hospital, Shanghai Jiao Tong University School of Medicine, led by a team of urology and molecular medicine researchers. A total of 500 male participants aged 18 years or older who meet clinical indications for prostate biopsy will be enrolled between May 2026 and May 2027. All participants have suspected prostate cancer (PCa) based on abnormal prostate-specific antigen (PSA), abnormal digital rectal examination (DRE), suspicious multiparametric MRI (mpMRI), positive family history of prostate cancer, pathogenic gene mutations, or other high-risk clinical findings. Men with confirmed treated prostate cancer, recent prostate-related procedures, active other malignancies, severe organ dysfunction, coagulation disorders, or cognitive impairment that prevents informed consent will be excluded. The core goal of this study is to test the diagnostic performance of a novel non-invasive blood test using a panel of circulating microRNAs (miRNAs) from serum, and compare it with the standard PSA-based screening tools to distinguish prostate cancer from benign prostatic hyperplasia (BPH). The gold standard for judging true disease status will be pathology results from transrectal ultrasound-guided prostate biopsy. Researchers will calculate key diagnostic metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC curve (AUC) for the miRNA panel. Secondary analyses will evaluate whether combining the miRNA signature with PSA or mpMRI improves diagnostic accuracy, especially for men with PSA levels in the ambiguous "gray zone" of 4-10 ng/mL. Subgroup assessments will also test how well the miRNA panel differentiates low-risk versus high-risk prostate cancer and clinically significant versus insignificant tumors across different PSA tiers, age groups, mpMRI risk scores and prostate sizes. Additional laboratory testing will confirm the stability of serum miRNAs under different storage temperatures and storage durations, as well as test consistency across operators, reagent batches and detection platforms to validate real-world clinical usability. For participants, the study only involves a one-time fasting venous blood draw of up to 10 mL before biopsy, with no extra invasive procedures or experimental medications added to routine clinical care. The free miRNA test results can serve as supplementary evidence to help doctors judge whether a prostate biopsy is truly necessary, potentially sparing many patients from unnecessary invasive biopsy and its associated discomfort or complications. All blood samples will be stored under standardized biosafety protocols with de-identified personal data to fully protect participant privacy. Minimal risks include minor temporary bruising or slight pain at the blood draw site, which resolve spontaneously without long-term harm. Statistical analysis will use three defined datasets (full analysis set, per-protocol set, safety set) and advanced methods including DeLong's test, logistic regression, NRI and IDI to quantify diagnostic improvement versus PSA. A 70% training cohort will build the miRNA diagnostic model, and the remaining 30% of samples will act as an independent validation group to verify model reliability. Safety monitoring will record all adverse events throughout follow-up, with strict ethical oversight following the Declaration of Helsinki and Chinese biomedical research regulations. After sample testing, data analysis and result summarization finish by October 2027, the research team plans to publish 1-2 peer-reviewed SCI papers to share findings globally. If validated, this serum miRNA panel will provide a more precise, non-invasive screening tool to reduce overdiagnosis and unnecessary prostate biopsies, optimize early prostate cancer detection, and lower overall medical burdens for men at risk of prostate disease in clinical practice.

Sex

Male

Minimum age

18 Years

Inclusion Criteria:

Male participants aged ≥18 years Serum PSA \> 4.0 ng/mL confirmed by repeat testing with ≥4-week interval, excluding interfering conditions such as acute urinary retention, catheterization and prostatitis PSA within gray zone (4.0-10.0 ng/mL) accompanied by abnormal f/t PSA ratio \<0.16, PSAD \>0.15 ng/mL/g or PSAV \>0.75 ng/mL/year Persistently rising PSA on two consecutive tests with abnormal PSAV regardless of absolute PSA value Abnormal digital rectal examination (DRE): palpable hard, nodular, fixed or asymmetric prostate lesions, indistinct induration or suspected space-occupying lesions Suspicious transrectal ultrasound (TRUS): hypoechoic nodules, hypervascular areas or disrupted prostatic capsule mpMRI PI-RADS v2.1 score ≥3, especially lesions scoring 4-5 Elevated focal PSMA uptake on PSMA PET/CT (if performed) First-degree relative with prostate cancer and personal PSA \>3.0 ng/mL Carriers of pathogenic BRCA1/2, HOXB13 mutations with PSA \>3.0 ng/mL Prior negative prostate biopsy with subsequent sustained PSA elevation or new suspicious mpMRI lesions Unexplained bone pain or pathological fracture with elevated PSA requiring exclusion of primary prostate malignancy Aggravated bladder outlet obstruction with elevated PSA or abnormal DRE requiring differentiation of malignant obstruction

Exclusion Criteria:

Confirmed prostate cancer receiving radical surgery, radiotherapy, androgen deprivation therapy or active surveillance Acute bacterial prostatitis, febrile urinary tract infection or acute urinary retention within the preceding 4 weeks Prostate massage, cystoscopy, ejaculation within 72 hours; prostate biopsy within 6 weeks; transurethral prostate surgery within 3 months prior to screening Active concurrent malignancy or history of any malignant tumor within the past 5 years (non-melanoma skin cancer excluded) Severe Child-Pugh grade C liver dysfunction, eGFR \<30 mL/min/1.73m², coagulopathy (INR \>1.5 or platelet count \<50×10⁹/L) Unable to discontinue anticoagulants (warfarin, dabigatran, rivaroxaban) or dual antiplatelet therapy for ≥5 days Severe cognitive impairment or acute psychiatric disorder precluding independent informed consent, follow-up and biospecimen collection Participation in other interventional clinical trials within 3 months or concurrent observational trials interfering with study outcomes Hematological disorders including myelodysplastic syndrome and leukemia that alter serum nucleic acid stability Severe peripheral vascular disease hindering venipuncture or inability to comply with fasting blood collection requirements