**Core Concept:** Prostate cancer (PCa) is a common malignancy in males, particularly in those with a positive family history, where early detection can lead to better treatment outcomes and improved prognosis. Screening tests aim to identify precancerous or early-stage PCa.

**Why the Correct Answer is Right:** The most sensitive screening test for prostate cancer is Prostate Specific Antigen (PSA) test. PSA is a protein produced by both normal prostate cells and cancerous cells, making it an indirect marker for prostate health. Elevated PSA levels can indicate either cancer or benign prostatic hyperplasia (BPH).

**Why Each Wrong Option is Incorrect:**
A. Digital Rectal Examination (DRE) is a physical examination technique that evaluates prostate size, consistency, and symmetry. While helpful, it lacks sensitivity due to its dependence on the examiner's skill and the presence of cancerous lesions.

B. Transrectal ultrasound (TRUS) is an imaging technique used to visualize the prostate and assess its size and shape. While useful for size estimation, it is not as sensitive as PSA in detecting cancer due to its dependence on cancer size and location within the prostate.

C. Prostate Cancer Antigen 3 (PCA3) gene is a molecular marker that can be detected in urine and has been associated with prostate cancer risk. While showing promise, PCA3 testing is not as widely available or standardized as PSA testing.

D. Prostate Health Index (PHI) is a combination of PSA, age, and DRE score to predict prostate cancer risk. While improving predictive accuracy, PHI is not as sensitive as PSA alone in detecting cancer due to its dependence on PSA levels.

**Clinical Pearl:** Early detection and treatment of prostate cancer can improve patient outcomes. However, it is essential to consider the patient's clinical scenario and disease stage when deciding on the most appropriate screening test. A combination of PSA testing and DRE may be warranted in high-risk patients like our 50-year-old male with positive family history.