What is the typical spread path of prostate cancer?

Typical Spread Path of Prostate Cancer

Prostate cancer disseminates through three primary pathways: local extension through the prostatic capsule, lymphatic spread to regional and pelvic lymph nodes, and hematogenous spread predominantly to bone (occurring in 84% of metastatic cases). 1

Primary Routes of Dissemination

Local Extension

• Prostate cancer begins with local invasion through the prostatic capsule, progressing from the urothelium through the lamina propria into the muscularis propria (detrusor muscle), and subsequently into the perivesical fat. 1
• The anatomic progression follows a predictable sequence through stages T1-T2 (confined to prostate), T3a (extracapsular extension), T3b (seminal vesicle invasion), and T4 (invasion of adjacent structures). 1
• Seminal vesicle invasion occurs via direct tumor spread into the midbase region near the ejaculatory ducts in 98% of cases (46/47 cases studied). 2
• Approximately 70-85% of bladder urothelial carcinomas are non-muscle invasive at presentation, but invasion of the muscularis propria significantly increases risk for distant spread. 3

Lymphatic Dissemination

• Regional lymph nodes include pelvic nodes below the bifurcation of the common iliac arteries, with nodes ≥1.5 cm in short axis considered pathologically enlarged and measurable. 3, 1
• Pelvic nodal disease is classified as locoregional, while extrapelvic nodes (retroperitoneal, mediastinal, thoracic) are classified as metastatic (M1a disease). 3
• Lymph nodes between 1.0-1.5 cm in short axis may be pathologic and can be considered non-measurable/non-target lesions. 3
• Approximately 14% of patients present with regional lymph node metastases at diagnosis. 4

Hematogenous Spread

• Hematogenous dissemination occurs predominantly after muscularis propria invasion, dramatically increasing the risk of distant metastases. 1
• The most common metastatic sites in order of frequency are: bone (84%), distant lymph nodes (10.6%), lung (9.1%), liver (10.2%), and other sites including adrenal glands and CNS. 1, 5
• Approximately 10% of patients present with distant metastases (M1 disease) at diagnosis, associated with a 5-year survival rate of 37%. 4

Clinical Subtypes Based on Pattern of Spread

The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) defines five distinct clinical subtypes that are prognostically important: 3, 5

1. Locally recurrent/persistent disease: CRPC in the prostate or prostate bed after surgery or radiation, with no evidence of metastases on imaging
2. Non-metastatic CRPC (nmCRPC): Rising PSA without detectable disease in primary site, lymph nodes beyond pelvis, bone, or visceral organs
3. Nodal disease only: Lymph node spread within pelvis (>1.0 cm) and/or beyond pelvis, without bone or visceral disease
4. Bone disease: Skeletal metastases with or without nodal disease, but no visceral spread
5. Visceral disease: Metastases to lung, liver, adrenal, or CNS, with or without spread to other sites (each reported separately)

Important Clinical Considerations

Prognostic Factors

• PSA doubling time (PSADT) <6 months strongly suggests metastatic dissemination rather than local recurrence. 6
• The presence of visceral metastases indicates more aggressive disease and poorer prognosis compared to bone-only metastases. 5
• Patients with castration-resistant prostate cancer and bone metastases have a median survival of <2 years. 5

Diagnostic Imaging Recommendations

• Contrast-enhanced CT of chest, abdomen, and pelvis with ≤5 mm axial slices is recommended for all metastatic patients to assess nodal and visceral disease. 3
• Chest CT imaging is specifically recommended given the 7% prevalence of lung metastases in castration-resistant prostate cancer trials. 3, 5
• PSMA PET/CT has significantly superior accuracy compared to conventional imaging for detecting visceral metastases and is now the preferred imaging modality when available. 6
• Bone scintigraphy remains the standard for detecting skeletal metastases. 5

Common Pitfalls

• Seminal vesicle invasion may be missed if tissue nearest the ejaculatory ducts at the prostate base is not adequately sampled during pathologic examination. 2
• Bone metastases may paradoxically appear worse on imaging despite effective treatment (flare phenomenon), leading to false interpretation of disease progression. 5
• CT, ultrasound, and MRI cannot always accurately predict the true depth of local invasion. 6
• A single negative imaging study does not definitively rule out metastatic disease when clinical suspicion is high. 6