Definition of Low-Volume and High-Volume Metastatic Prostate Cancer
High-volume metastatic prostate cancer is defined as the presence of visceral metastases (lung or liver) and/or four or more bone metastases with at least one metastasis located outside of the vertebral column and pelvis; all other metastatic disease is classified as low-volume. 1
Standard CHAARTED Criteria (Guideline-Based Definition)
The AUA/ASTRO/SUO guidelines and NCCN guidelines both endorse the CHAARTED trial definition as the standard classification system for clinical practice: 1
High-Volume Disease Criteria (Must Meet ONE of the Following):
- Visceral metastases: Presence of metastases in the lungs or liver 1
- Extensive bone metastases: Four or more bone lesions with at least one lesion beyond the spine and pelvis (appendicular skeleton involvement) 1
Low-Volume Disease:
- All metastatic disease that does not meet high-volume criteria 1, 2
- This includes patients with 1-3 bone metastases, or 4+ bone metastases confined only to the spine and pelvis 2
Clinical Significance and Treatment Implications
The volume classification directly determines treatment intensity and predicts survival outcomes: 1, 2
High-Volume Disease:
- Median overall survival: 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR 0.63, P<0.001) 2
- Strong recommendation: ADT plus docetaxel chemotherapy or novel hormonal therapy (abiraterone/enzalutamide) 1
- Approximately 65% of metastatic patients present with high-volume disease 1, 2
Low-Volume Disease:
- No survival benefit demonstrated with docetaxel added to ADT (HR 1.04, P=0.86) 2
- Preferred treatment: Novel hormonal therapy doublets (ADT plus abiraterone or enzalutamide) with or without metastasis-directed therapy 3
- Docetaxel doublets have no clear role in low-volume disease 3
Alternative Volume Definitions (Less Commonly Used)
While 61% of expert panelists accept the CHAARTED definition, alternative classifications exist but are not standard: 1
- SWOG definition: Visceral metastases and/or any appendicular skeletal involvement (more inclusive than CHAARTED) 1
- Glass definition: Diffuse bone disease involving chest, head, extremities, and/or visceral organ involvement 1
Critical Assessment Requirements
Before classifying disease volume, clinicians must: 1
- Assess all metastatic sites: Bone, lymph node, and visceral metastases using conventional imaging (CT, MRI, bone scintigraphy) 1
- Document precise locations: Specifically identify whether bone metastases extend beyond the vertebral column and pelvis 1, 4
- Count bone lesions accurately: Enumerate total bone metastases and their anatomic distribution 1, 4
Important Caveats and Pitfalls
Impact of Advanced Imaging:
- PSMA PET imaging detects more metastases than conventional imaging, leading to stage migration in 40% of patients 5
- Every third patient with low-volume disease on conventional imaging is downstaged to M0 on PSMA PET 5
- Every fifth patient with low-volume disease is upstaged to high-volume on PSMA PET 5
- Current treatment guidelines are based on conventional imaging (CT/MRI/bone scan), not PSMA PET, so volume classification should use conventional imaging for treatment decisions 1, 5
Quantitative Bone Burden Refinement:
- Among high-volume patients without visceral metastases, those with bone scan index beyond vertebrae/pelvis (bBSI) ≤0.27 have survival comparable to low-volume disease 4
- A modified CHAARTED definition incorporating bBSI >0.27 improves prognostic accuracy (HR 4.69 vs. 4.33 for original criteria) 4
Heterogeneity Within High-Volume Disease:
- Patients with high-volume disease limited to extent-of-disease categories 1-2 (HV-EOD1-2) show no worse prognosis than low-volume disease 6
- Lung metastases alone do not worsen prognosis compared to bone-only disease (HR 1.29, P=0.29) 6