What are the definitions of low‑volume and high‑volume prostate cancer according to the CHAARTED (Chemohormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease) criteria?

CHAARTED Criteria for Prostate Cancer Volume Classification

According to the CHAARTED criteria, high-volume metastatic prostate cancer is defined as the presence of visceral metastases (lung or liver) and/or ≥4 bone metastases with at least one metastasis outside of the vertebral column and pelvis; low-volume disease is defined as anything that does not meet these high-volume criteria. 1

High-Volume Disease Definition

The CHAARTED high-volume criteria specifically require:

• ≥4 bone metastases with at least one beyond the spine/pelvis, OR
• Visceral metastases (lung or liver involvement) 1

This definition was established in the landmark CHAARTED trial (E3805) and has been adopted by major guidelines including the AUA/ASTRO/SUO and NCCN 1. The presence of high-volume disease carries significant prognostic implications, with median overall survival of 34.4 months with ADT alone versus 51.2 months with chemohormonal therapy 2.

Low-Volume Disease Definition

Low-volume disease encompasses all metastatic presentations that do not meet high-volume criteria 1. This includes:

• <4 bone metastases, OR
• ≥4 bone metastases confined to the spine and pelvis only
• No visceral metastases 1

Patients with low-volume disease demonstrate substantially better prognosis, with median overall survival not reached in the CHAARTED trial at 53.7 months follow-up 2, 3.

Clinical Application and Treatment Implications

The volume classification directly impacts treatment selection in metastatic hormone-sensitive prostate cancer (mHSPC). 1

High-Volume Disease Management:

• Triplet therapy with ADT + docetaxel + novel hormonal agent (abiraterone or darolutamide) is the preferred approach for fit patients with high-volume de novo disease 1
• Chemohormonal therapy (ADT + docetaxel) showed clear survival benefit in high-volume patients (HR 0.63; 95% CI 0.50-0.79; P<0.001) 2, 3
• Novel hormonal agents alone with ADT (abiraterone, apalutamide, or enzalutamide) are alternatives when chemotherapy is not feasible 1

Low-Volume Disease Management:

• No survival benefit was demonstrated with docetaxel addition in low-volume disease (HR 1.04; 95% CI 0.70-1.55; P=0.86) 2, 3
• Novel hormonal agents with ADT (abiraterone, apalutamide, or enzalutamide) are recommended as first-line treatment 1
• ADT alone may be considered in vulnerable patients who cannot tolerate treatment intensification 1

Important Caveats and Considerations

Alternative Volume Definitions:

While CHAARTED criteria are most widely adopted, 61% of expert panelists endorsed the CHAARTED definition for clinical practice 1. Alternative definitions exist:

• SWOG definition: visceral metastases and/or any appendicular skeletal involvement 1
• Glass definition: diffuse bone disease (chest, head, extremities) and/or visceral involvement 1

Agreement with LATITUDE High-Risk Criteria:

The CHAARTED high-volume definition shows "almost perfect" agreement (Cohen's κ=0.83) with LATITUDE high-risk criteria (≥2 of: Gleason ≥8, ≥3 bone lesions, visceral metastases) 4. Both definitions demonstrate similar prognostic significance for castration-resistant progression-free survival and overall survival 4.

PSMA PET Imaging Considerations:

Conventional imaging (CT/MRI with bone scan) remains the standard for volume classification because pivotal trials used these modalities 1. However, PSMA PET leads to stage migration in 40% of patients, with 22% of conventional low-volume patients upstaged to high-volume and 30% downstaged to M0 5. Future volume definitions may require adjustment for PSMA PET-based staging 5.

Racial Considerations:

Asian populations may require different thresholds, with exploratory data suggesting ≥11 bone metastases (rather than ≥4) as a more appropriate high-volume definition in this population 6. This reflects racial differences in treatment response and outcomes 6.

Assessment Requirements:

Clinicians must assess extent of metastatic disease using conventional imaging (CT, MRI, and 99mTc-methylene diphosphonate bone scan) before treatment initiation 1. The assessment should document:

• Number and location of bone metastases (specifically noting lesions beyond spine/pelvis)
• Presence of visceral metastases (lung, liver)
• Lymph node involvement 1