Study on Triple Therapy Combined With HIFU for High-Tumor-Burden mHSPC

Inclusion Criteria

• Patients who agree to participate in the study and sign the informed consent form.
• Age ≥18 years, male.
• Histologically or cytologically confirmed prostate adenocarcinoma.
• Bone scan, CT, or MRI showing ≥4 bone metastases (with ≥1 outside the pelvis or spine) or visceral metastases.
• Newly diagnosed or recurrent disease after local therapy, with sensitivity to androgen deprivation therapy (ADT).
• Patients who have received ADT (medical or surgical castration) with or without first-generation antiandrogens for ≤3 months, without evidence of soft tissue disease progression (per RECIST 1.1) or clinically significant PSA progression (≥50% increase from nadir with serum testosterone at castrate levels).
• Planned treatment with docetaxel plus apalutamide and ADT, or apalutamide plus ADT.
• ECOG Performance Status (PS) score of 0-1.
• Adequate hematologic and organ function:
  • **Bone marrow function (without transfusion or growth factor support):**
  • Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L (1500/μL)
  • Hemoglobin ≥90 g/L (9.0 g/dL)
  • Platelet count ≥100 × 10⁹/L (100,000/μL)
  • **Liver function:**
  • Total bilirubin (TBIL) ≤1.5 × ULN
  • AST, ALT, and alkaline phosphatase (ALP) ≤2.5 × ULN
  • **Renal function:**
  • Serum creatinine ≤1.5 × ULN **or** calculated creatinine clearance ≥30 mL/min (Cockcroft-Gault formula)
  • **Coagulation function (without anticoagulation therapy):** INR ≤1.5
• Patients of reproductive potential must use effective contraception during the study and for 6 months after the last dose.

Exclusion Criteria

• Lesions located at the prostate apex or in areas inaccessible for focal therapy.
• Beaded prostatic calculi or cysts >1 cm in diameter within the treatment or ultrasound pathway.
• Urethral stricture or presence of metal/other implants in the urethra.
• Prior rectal surgery.
• History of or existing rectal fistula.
• Rectal stenosis preventing transrectal ultrasound.
• Rectal invasion.
• Active severe urinary tract infection.
• Severe cardiovascular or cerebrovascular disease affecting anesthesia/surgery.
• History of hypersensitivity or intolerance to any study drugs.
• Planned concurrent anticancer therapy during the study.
• Prior treatment with second-generation androgen receptor (AR) inhibitors (e.g., apalutamide, enzalutamide, darolutamide), CYP17 inhibitors (e.g., abiraterone acetate, ketoconazole), chemotherapy, immunotherapy, or adjuvant/neoadjuvant therapy.
• Use of herbal products with anti-prostate cancer or PSA-lowering effects (e.g., saw palmetto) within 4 weeks before study treatment.
• History of seizures, medications that lower seizure threshold, or conditions predisposing to seizures within 12 months (including TIA, stroke, or traumatic brain injury with hospitalization).
• Active cardiac disease within 6 months before treatment: severe/unstable angina, myocardial infarction, congestive heart failure (NYHA Class III/IV), or arrhythmia requiring medication.
• Conditions impairing drug absorption (e.g., dysphagia, chronic diarrhea, intestinal obstruction).
• Immunodeficiency (e.g., HIV-positive, congenital/acquired immunodeficiency) or organ transplant history.
• Known brain metastases.
• Other malignancies within 5 years (except cured basal cell carcinoma or cervical carcinoma in situ).
• Concurrent participation in another investigational drug/device trial.
• Poor compliance likely to hinder treatment/follow-up.
• Uncontrolled comorbidities (e.g., hypertension, diabetes, neuropsychiatric disorders) that may compromise safety or confound results, per investigator judgment.
• Any other condition deemed unsuitable for inclusion by the investigator.