The formatting doesn't come through.
BAT in HSPC (HSPC Classification)
Key Definitions
1. HSPC (Hormone-Sensitive Prostate Cancer):
• Cancer responds to androgen deprivation therapy (ADT) with testosterone <50 ng/dL, evidenced by:
• PSA suppression:
• Post-radical prostatectomy (RP): Sustained PSA <0.1 ng/mL.
• Non-surgical management: PSA <1 ng/mL.
• No radiographic or clinical progression during long-term ADT.
2. CRPC (Castration-Resistant Prostate Cancer):
• PSA progression (≥2 ng/mL rise from nadir, confirmed ≥3 weeks apart) despite castrate testosterone (<50 ng/dL).
BAT in HSPC: Mechanism and Goals
• Objective: Disrupt adaptive AR upregulation during ADT to delay CRPC onset.
• Mechanism:
1. SPA Phase: Supraphysiologic testosterone (1,500+ ng/dL) induces DNA damage in AR-overexpressing cells via replication stress.
2. Low-T Phase: Rapid testosterone withdrawal (<50 ng/dL) triggers apoptosis in cells dependent on AR signaling.
• PSA Dynamics:
• SPA Phase: PSA rises (e.g., 2.0 ng/mL) due to AR activation (expected, not indicative of resistance).
• Low-T Phase: PSA declines (e.g., 0.7 ng/mL, 65% reduction) if tumors remain hormone-sensitive.
Case-Specific Analysis
• Example Patient:
• SPA Phase: PSA = 2.0 ng/mL (AR-driven growth).
• Low-T Phase: PSA = 0.7 ng/mL (65% decline).
• Implications:
• HSPC Confirmation: A PSA nadir <1 ng/mL post-BAT meets HSPC criteria.
• Lack of Progression: No new metastases or symptoms during long-term ADT.
• BAT’s Role: Cyclical design prevents AR adaptation, extending hormone sensitivity.
Conclusion
BAT is a proactive strategy in HSPC to delay CRPC by leveraging cyclical androgen fluctuations. A PSA decline to <1 ng/mL post-BAT confirms sustained hormone sensitivity, while the absence of progression solidifies the HSPC classification.
Definition of Progression from HSPC to CRPC
Progression from hormone-sensitive prostate cancer (HSPC) to castration-resistant prostate cancer (CRPC) is defined by the following criteria, consistent with international guidelines (e.g., EAU, NCCN):
1. Castrate Testosterone Levels
• Serum testosterone <50 ng/dL (or <1.7 nmol/L) during androgen deprivation therapy (ADT).
2. Evidence of Disease Progression
Progression is confirmed by either biochemical (PSA) or radiographic criteria:
Biochemical Progression Radiographic Progression
All of these:
• Three consecutive PSA rises (≥1 week apart).
• Each PSA value ≥50% above the nadir (lowest PSA on ADT).
• Absolute PSA ≥2.0 ng/mL. Either of these:
• New lesions on imaging (bone scan, CT, MRI).
• Growth of existing lesions (≥20% increase in measurable soft tissue lesions).
Key Notes
• CRPC Subtypes:
• Nonmetastatic CRPC (nmCRPC): PSA progression without detectable metastases.
• Metastatic CRPC (mCRPC): Progression with radiographically confirmed metastases.
• Exclusions: Progression due to non-cancer causes (e.g., urinary tract infection) must be ruled out.
Clinical Implications
• Therapeutic Shift: Progression to CRPC mandates a transition from ADT to CRPC-specific therapies (e.g., ARSIs, PARP inhibitors, radioligands).
• Prognostic Factors:
• Shorter time to CRPC is linked to:
• Metastases at diagnosis.
• PSA nadir >2 ng/mL.
• Rapid PSA decline during ADT (paradoxically associated with earlier resistance).
• High Gleason score (≥8).
First BAT cycle results: what next?
Enzalutamide & ARCHES trial.
Androgen Receptor Activity (ARA) for BAT
