Low-Risk Metastatic Castration-Sensitive Prostate Cancer: Definition and Criteria
Low-risk metastatic castration-sensitive prostate cancer (mCSPC) is defined by the absence of high-risk features established in the LATITUDE trial: patients who do NOT have at least 2 of the following criteria: Gleason score 8-10, ≥3 bone metastases, or visceral metastases. 1
Primary Classification System: LATITUDE High-Risk Criteria
The most clinically relevant definition comes from the LATITUDE trial, which established high-risk disease as having at least 2 of 3 features: 1
- Gleason score 8-10
- ≥3 bone metastases
- Visceral metastases (lung, liver, or other organs)
Patients with 0 or 1 of these features are considered low-risk mCSPC. 1
Alternative Classification: CHAARTED Volume-Based Criteria
A complementary system defines disease burden by metastatic volume rather than risk: 2, 3
- Low-volume disease: Absence of visceral metastases AND fewer than 4 bone metastases (with none outside the vertebral bodies/pelvis) 2, 3
- High-volume disease: Visceral metastases OR ≥4 bone metastases with ≥1 beyond the vertebral column/pelvis 2, 3
Simplified Numeric Definitions
Recent comparative analyses suggest numeric cutoffs may be equally valid and simpler to apply: 3
- ≤3 bone metastases = low-volume
- ≤5 bone metastases = low-volume
These numeric definitions showed similar prognostic discrimination to CHAARTED and LATITUDE criteria, with 84.7% of patients classified identically across all four definitions. 3
Critical Clinical Distinctions
The majority of patients (84.7%) are classified consistently across all four definitions, suggesting these systems capture similar biological behavior. 3 However, patients with discordant classifications (e.g., low-volume by CHAARTED but high-risk by LATITUDE) tend to have more aggressive disease and worse outcomes. 3
Patients with low-volume disease but TP53 mutations demonstrate radiographic progression-free survival similar to high-volume disease, indicating that molecular features may refine risk stratification beyond anatomic criteria alone. 3
Treatment Implications for Low-Risk/Low-Volume Disease
The survival benefit of treatment intensification is less clear in low-risk/low-volume mCSPC compared to high-risk/high-volume disease. 2, 4 Meta-analyses have failed to demonstrate significant survival benefits for all upfront combination therapies in the low-volume subgroup, with significance observed only for enzalutamide and radiation to the prostate. 2
Men with low-volume, low-risk mCSPC who have favorable response to ADT can achieve long-term survival with ADT alone, and toxicities from combination therapies may exceed benefits in this subset. 2, 5
Common Pitfalls to Avoid
Do not confuse "low-risk mCSPC" with "low-risk localized disease"—these are entirely different entities with different treatment paradigms. Low-risk localized disease (T1-T2a, Gleason ≤6, PSA <10) may be managed with active surveillance, while low-risk mCSPC still requires systemic therapy. 1
Do not assume all mCSPC patients require triplet therapy—this represents potential overtreatment in the low-risk/low-volume subset where doublet therapy or even ADT alone may be appropriate based on individual patient factors and response. 2, 5
Recognize that PET imaging with PSMA tracers identifies oligometastatic disease (particularly nodal-only) that would not meet conventional RECIST criteria—this population has not been specifically studied in phase III trials and may warrant different treatment approaches. 5