Efficacy and Safety of Darolutamide Combined With Docetaxel and ADT as Neoadjuvant Therapy for Locally Advanced Prostate Cancer.

Inclusion Criteria:

1. Male, age >= 18 years and <= 75 years at the time of signing the informed consent form;
2. Confirmed as prostate cancer by histological or cytological examination, and planned for radical prostatectomy;
3. Clinical stage conforms to the definition of locally advanced prostate cancer: cT3b-cT4, N0, M0 or any cT, N1, M0 (based on PSMA-PET/CT examination);
4. Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1;
5. Expected lifespan >= 10 years;
6. Important laboratory indicators meet the following requirements: a. Hemoglobin >= 90 g/L b. Serum total bilirubin <= 1.5 times the upper limit of normal value, transaminase (AST/ALT) <= 2.5 times the upper limit of normal value c. Serum albumin >= 30 g/L d. Serum creatinine <= 1.5 times the upper limit of normal value e. Absolute neutrophil count >= 1.5 x 10^9/L, platelet count >= 100 x 10^9/L;
7. No difficulty in swallowing (can take the medicine in whole), chronic diarrhea, intestinal obstruction or other factors affecting drug administration and absorption;
8. No use of opioid analgesics (including codeine, oxycodone, etc.) to relieve cancer pain;
9. If the spouse is a fertile female, the subject consents to take effective contraceptive measures during the treatment period and for 4 months after the surgery;
10. The subject voluntarily participates in this trial, signs the informed consent form, and is willing to comply with the requirements of the research protocol throughout the study period.

Exclusion Criteria:

1. Pathological diagnosis of neuroendocrine prostate cancer, including small cell carcinoma;
2. Prior local or systemic treatment for prostate cancer, including but not limited to radiotherapy, chemotherapy, or endocrine therapy;
3. Confirmed bone metastasis, hepatic metastasis, brain metastasis, or other visceral metastases on imaging;
4. Known hypersensitivity to the study drugs (active ingredients or excipients) or drugs of the same class;
5. Contraindications to prednisone acetate or docetaxel, such as active infection, allergy, or other conditions;
6. Chronic disease requiring prednisone acetate at doses exceeding those specified in the protocol (5 mg orally twice daily, starting 14 days before docetaxel chemotherapy and stopping 3 weeks after the last chemotherapy cycle);
7. Poorly controlled hypertension despite medication (systolic blood pressure >=160 mmHg or diastolic blood pressure >=95 mmHg);
8. Active or symptomatic viral hepatitis or other chronic liver disease; known human immunodeficiency virus (HIV) infection;
9. History of pituitary or adrenal dysfunction;
10. Active autoimmune disease requiring hormonal therapy;
11. Major cardiovascular or cerebrovascular disease within 6 months prior to the start of study treatment, including: severe/unstable angina, myocardial infarction, congestive heart failure [New York Heart Association (NYHA) class III or above], cerebrovascular accident, or arrhythmia requiring pharmacological treatment;
12. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
13. Grade ≥2 peripheral sensory or motor neuropathy;
14. Other malignancies occurring within the past 2 years or currently concurrent malignancies;
15. Major surgery requiring general anesthesia within 28 days before the first dose;
16. Treatment with strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ketoconazole) or strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, phenobarbital, St. John's wort) that cannot be discontinued, and have not been stopped for at least 7 days before randomization;
17. History of epilepsy;
18. Alcohol or drug abuse or dependence;
19. Participation in another therapeutic clinical study within 1 month before the start of study treatment;
20. Any other condition that the investigator considers unsuitable for participation in this study;