How do you differentiate between Benign Prostatic Hyperplasia (BPH) and prostate cancer?

Differentiation of BPH and Prostate Cancer

Digital rectal examination (DRE) combined with PSA testing are the primary clinical tools to differentiate BPH from prostate cancer, with a nodular abnormality on DRE indicating approximately 50% probability of cancer on biopsy, while histological confirmation via prostate biopsy remains necessary for definitive diagnosis in almost all cases. 1

Mandatory Initial Clinical Assessment

The differentiation process begins with specific clinical findings that distinguish these conditions:

Digital Rectal Examination (DRE)

• DRE is mandatory for all patients presenting with lower urinary tract symptoms, as it provides critical information about prostate characteristics 2, 3
• A nodular or irregular prostate on DRE suggests malignancy with ~50% positive predictive value for cancer on subsequent biopsy 1
• DRE assesses prostate size (relevant for BPH management) and can detect locally advanced prostate cancer 3
• A smooth, symmetrically enlarged prostate is more consistent with BPH 1

PSA Testing and Interpretation

• PSA should be offered to patients with at least 10-year life expectancy when knowledge of prostate cancer would change management 3
• Approximately 25% of men with BPH have PSA >4.0 ng/mL, creating diagnostic overlap 4, 3
• The 4-10 ng/mL range represents a "diagnostic gray zone" where only 25-30% of men actually have cancer on biopsy 4
• PSA is more highly expressed gram-for-gram in hyperplastic tissue than in cancer tissue, making it a better marker of BPH severity than cancer presence 4

Advanced Diagnostic Strategies When PSA is Elevated

When PSA elevation occurs, use these refined approaches:

Free-to-Total PSA Ratio

• For PSA 4-10 ng/mL, obtain free-to-total PSA ratio to improve diagnostic specificity 4
• Cancer patients have lower percentage of free PSA compared to BPH patients 4
• This ratio is less useful in prostates >60 mL due to larger proportion of benign tissue (specificity drops to 56% vs 86% in smaller prostates) 5

PSA Velocity (PSAV)

• PSAV >0.75 ng/mL per year suggests cancer with 79% sensitivity when PSA is 4-10 ng/mL 4
• Requires at least 3 measurements over 18 months for accuracy 4
• Very high PSAV may indicate prostatitis rather than cancer, requiring clinical correlation 4

PSA Density (PSAD)

• PSAD (serum PSA ÷ prostate volume) provides superior differentiation compared to absolute PSA values 6
• Mean PSAD is 0.116 for BPH vs 0.46 for prostate cancer (p<0.005) 6

Critical Confounding Factors to Exclude

Before attributing elevated PSA to cancer, rule out these causes:

Prostatitis

• Wait 4-6 weeks after complete resolution of prostatitis symptoms before rechecking PSA 4
• Prostatitis causes dramatic, abrupt PSA increases that can take 6-8 weeks to normalize 4
• Physical activity, sexual activity, recent instrumentation, or kidney stones can elevate PSA—wait 2-6 weeks before retesting 4

Medications

• 5α-reductase inhibitors (finasteride, dutasteride) reduce PSA by ~50% within 6-12 months, though this is highly variable 4, 7
• Failure to achieve expected PSA decrease on these medications indicates heightened cancer risk 4

When to Proceed to Biopsy

Histological confirmation via prostate biopsy is required in almost every case for definitive cancer diagnosis 1. Consider biopsy when:

• PSA persistently elevated after excluding confounding factors 4
• Abnormal DRE findings (nodularity, asymmetry, induration) 1
• Concerning PSA velocity or free-to-total PSA ratio 4
• PSA density suggestive of malignancy 6

Optional Diagnostic Tests

Urethrocystoscopy

• Appropriate for patients with hematuria, history of urethral stricture, bladder cancer, or prior lower urinary tract surgery 8
• Not routinely necessary for BPH evaluation and should not be used to determine need for treatment 8
• Endoscopic appearance does not predict response to BPH therapy 8

Imaging

• Transabdominal ultrasound preferred over cystoscopy for anatomical assessment when surgery is considered 8
• Can measure prostate volume and identify intravesical lobes 8

Key Clinical Pitfalls to Avoid

• Do not rely on PSA alone—the false positive rate at PSA >4.0 ng/mL is 65% overall 4
• Do not ignore prostate volume when interpreting free-to-total PSA ratio, as it loses utility in prostates >60 mL 5
• Do not check PSA during or immediately after prostatitis—wait for complete resolution plus 4-6 weeks 4
• Screen for prostate cancer prior to initiating BPH treatment and at regular intervals, as the conditions frequently coexist 7, 1
• BPH is not a precursor to prostate cancer, though both increase with age and commonly coexist 1