Where does prostate cancer typically metastasize to?

Common Sites of Prostate Cancer Metastasis

Prostate cancer most commonly metastasizes to bone (84%), followed by distant lymph nodes (10.6%), liver (10.2%), and thorax (9.1%), with bone metastases being particularly prevalent in castration-resistant prostate cancer where >90% of patients develop skeletal involvement. 1, 2

Primary Metastatic Sites

• Bone: The skeletal system is overwhelmingly the most common site of metastasis, with 84% of metastatic prostate cancer patients having bone involvement 1
• Lymph nodes: Distant lymph node metastases occur in approximately 10.6% of patients with metastatic disease 1
• Liver: Hepatic metastases are present in about 10.2% of metastatic cases, representing the most common visceral metastatic site 1, 3
• Thorax/Lung: Pulmonary metastases occur in approximately 9.1% of metastatic prostate cancer patients, with a prevalence of about 7% in castration-resistant prostate cancer trials 1, 3
• CNS/Brain: Though less common, brain metastases can occur, particularly in patients who already have bone metastases 1
• Adrenal glands: Adrenal metastases are less common but can be detected on imaging studies 3

Pattern of Metastatic Spread

• About 18.4% of patients with metastatic prostate cancer have multiple metastatic sites involved 1
• Among patients with bone metastases, only 19.4% have multiple sites involved, suggesting bone-only disease is common 1
• In contrast, patients with metastases to other organs typically have multiple sites involved: liver (76.0%), thorax (76.7%), brain (73.0%), and kidney/adrenal gland (76.4%) 1
• When patients have bone metastases plus other sites, the most common secondary locations are liver (39.1%), thorax (35.2%), distant lymph nodes (24.6%), and brain (12.4%) 1

Clinical Subtypes Based on Pattern of Spread

The Prostate Cancer Clinical Trials Working Group 3 (PCWG3) defines five clinical subtypes based on pattern of spread 3:

1. Locally recurrent disease: After radical prostatectomy or radiation therapy with no evidence of metastases on imaging
2. Non-metastatic castration-resistant prostate cancer (nmCRPC): Rising PSA with no detectable disease on imaging
3. Nodal spread: Within the pelvis and/or beyond without bone or visceral disease
4. Bone disease: With or without nodal involvement but no visceral spread
5. Visceral disease: With or without spread to other sites, including lung, liver, adrenal, and CNS

Imaging Considerations for Detecting Metastases

• Bone metastases: Best detected using bone scintigraphy (bone scan), which may include SPECT for improved characterization 2
• Nodal and visceral metastases: Typically assessed with contrast-enhanced CT scan of chest, abdomen, and pelvis using ≤5-mm axial slices 3
• Lung metastases: Chest CT imaging is recommended due to the relatively frequent occurrence (7%) of pulmonary metastases in castration-resistant prostate cancer 3
• Liver metastases: CT is very accurate for evaluation of hepatic involvement 3

Clinical Implications

• The presence of visceral metastases generally indicates more aggressive disease and poorer prognosis than bone-only metastases 3
• Patients with castration-resistant prostate cancer and bone metastases have a median survival of <2 years 3
• Rare metastatic sites such as orbital metastases 4, renal pelvis/ureter 5, and paravertebral regions 6 have been reported and are associated with poor outcomes
• Understanding the pattern of metastatic spread is prognostic and should guide imaging strategies and treatment decisions 3

Monitoring Considerations

• Bone metastases may paradoxically appear worse on imaging despite effective treatment (flare phenomenon), which can lead to false interpretation of disease progression 3, 2
• PSA may not be a reliable marker of disease status in patients on androgen deprivation therapy, making imaging crucial for monitoring 3
• For patients with known metastatic disease, follow-up imaging should include assessment of all previously identified sites of disease 3