What is the diagnostic algorithm for prostate cancer?

Diagnostic Algorithm for Prostate Cancer

For men presenting with urinary symptoms or suspected prostate cancer, begin with serum PSA measurement and digital rectal examination (DRE), then proceed to transrectal ultrasound-guided prostate biopsy (minimum 10-12 cores) if either PSA is elevated or DRE is abnormal, followed by risk stratification and staging based on biopsy results. 1, 2

Initial Evaluation: First-Line Diagnostic Steps

Step 1: PSA Testing and DRE

• Measure serum PSA and perform DRE in all patients presenting with urinary symptoms 1, 2
• DRE is essential to exclude locally advanced prostate cancer and assess prostate size, texture, and nodularity 2
• A focused neurologic examination should also be performed 2

Step 2: Interpret PSA Results

• PSA 0-2 ng/mL: Probability of prostate cancer is 1% 1
• PSA 4-10 ng/mL: Consider measuring free/total PSA ratio; ratios <25% are associated with increased cancer risk 1, 3
• PSA >10 ng/mL: Probability of prostate cancer exceeds 50% 1, 4
• Important caveat: A single elevated PSA should not prompt immediate biopsy; verify with a second value 1

Step 3: Decision to Biopsy

Proceed to prostate biopsy if:

• DRE reveals abnormalities (nodularity, asymmetry, or induration) OR 1, 2
• PSA is elevated (particularly >4 ng/mL) OR 1
• Free/total PSA ratio is <25% in the 4-10 ng/mL range 1, 3

Consider patient factors before biopsy:

• Age, ethnicity (African American men have significantly increased risk), family history, and co-morbidities 1, 3
• Testing in asymptomatic men over age 70 is not recommended 1

Biopsy Technique and Specifications

Standard Biopsy Protocol

• Perform transrectal ultrasound (TRUS)-guided prostate biopsy 1, 2
• Obtain minimum of 10-12 cores from different areas of the peripheral prostate 1, 3
• Earlier guidelines recommended minimum 8 cores, but current standards favor 10-12 1
• Perform under antibiotic cover and local anesthesia 1

Pathology Reporting Requirements

• Report the extent of involvement of each biopsy core 1
• Report both the commonest and worst Gleason grades (using International Society of Urologic Pathology recommendations) 1
• The most dominant Gleason pattern and the pattern with highest grade determine the biopsy Gleason score 1

For Repeat Biopsies

• Before repeat biopsy, multi-parametric MRI is recommended with a view to MRI-guided or MRI-TRUS fusion biopsy 1
• This approach improves detection of clinically significant cancers and reduces detection of indolent disease 5

Risk Stratification and Staging After Positive Biopsy

Step 4: Initial Risk Assessment

Assess general health and co-morbidities first 1

• Patients unsuitable for curative treatment do not require extensive staging investigations 1

Step 5: Routine Staging Workup

For all patients with confirmed prostate cancer, obtain:

• Full blood count, alkaline phosphatase, creatinine, and serum total PSA 1, 4
• Clinical T stage evaluation by DRE 1, 2
• Chest X-ray 1

Step 6: Risk-Stratified Advanced Imaging

Low-risk disease (T1-2a, Gleason ≤6, PSA <10 ng/mL):

• No routine bone scan or advanced imaging needed 1

Intermediate or high-risk disease:

• Bone scintigraphy if: Gleason score >4+3 OR PSA >15 ng/mL OR bone metastases suspected clinically 1, 4
• Pelvic imaging (MRI or CT) if: Partin tables indicate >15% risk of nodal involvement 1
• Consider whole-body MRI or choline PET/CT for comprehensive staging 1

Step 7: Categorize into Risk Groups

Low-risk: T1-2a, Gleason ≤6, PSA <10 ng/mL 1 **Intermediate-risk:** T2b-T2c **OR** Gleason 7 **OR** PSA 10-20 ng/mL 1 **High-risk:** T3-T4 **OR** Gleason 8-10 **OR** PSA >20 ng/mL 1

Critical Pitfalls and Caveats

PSA Interpretation in Special Circumstances

• Men on 5α-reductase inhibitors (finasteride, dutasteride): PSA is reduced by approximately 50% after 3-6 months of treatment; double the PSA value for comparison with normal ranges 6, 7
• Any confirmed increase from the lowest PSA value while on these medications may signal prostate cancer, even if within normal range 6, 7
• Establish new PSA baseline at least 3-6 months after starting 5α-reductase inhibitor therapy 6, 7

Avoiding Overdiagnosis

• Population-based PSA screening is not recommended as it leads to overdiagnosis and overtreatment 1
• Subclinical prostate cancer is present in the majority of men over 50; only ~10% of latent cancers become clinically significant 1
• The effect of screening on mortality reduction comes at the cost of treating 27 patients to prevent one death 1

When Biopsy is Negative but Suspicion Remains

• Indications for repeat biopsy include: rising PSA, suspicious DRE, abnormal multi-parametric MRI, atypical small acinar proliferation, or multifocal high-grade prostatic intraepithelial neoplasia 1
• Always obtain multi-parametric MRI before repeat biopsy 1

Rare Presentation Alert

• Prostate cancer can present with low or minimally elevated PSA in rare cases, particularly with poorly differentiated tumors or PSA-nonproducing subclones 8
• Maintain high suspicion in patients with unexplained skeletal lesions regardless of PSA level 8