Darolutamide+ADT Post-RP w/o ePLND in hrPC: Briganti 2019

Inclusion criteria

• The patient volunteers to participate and signs the informed consent form (ICF);
• Age 18-75 years (inclusive), male;
• Histologically or cytologically confirmed prostatic adenocarcinoma;
• No non-regional lymph-node metastasis, bone metastasis, or other distant metastasis (e.g., visceral) by conventional imaging (bone scan, CT or MRI) or by PET/CT; i.e., M0;
• High-risk per the Briganti 2019 nomogram, i.e., risk >7%;
• PSA <0.1 ng/mL at 6 weeks after radical prostatectomy (RP);
• Has undergone RP without pelvic lymph-node dissection;
• Not suitable for adjuvant/salvage radiotherapy (RT) after RP, or the patient declines RT;
• Patients with lymph-node involvement (LNI) indicated by PSMA-PET who did not undergo extended pelvic lymph-node dissection (ePLND) may be enrolled;
• Patients with negative intraoperative obturator lymph-node biopsy who did not undergo ePLND may be enrolled;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1;
• Adequate hematologic and organ function:

• 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) (without transfusion and/or growth factors within 3 months prior to starting study treatment);
• Serum potassium ≥3.5 mmol/L;
• Total bilirubin (TBIL) ≤2.0 × ULN (for Gilbert syndrome, TBIL >1.5 × ULN is not eligible; if indirect bilirubin ≤1.5 × ULN, enrollment is allowed);
• AST and ALT ≤2.5 × ULN;
• Serum albumin ≥30 g/L (3.0 g/dL);
• Serum creatinine <2 × ULN;
• Patients of childbearing potential must agree to use effective contraception throughout the study and for 3 months after the last dose.

Exclusion criteria

• Histologic features of neuroendocrine differentiation or small-cell carcinoma;
• Prior prostate cancer treatments including any of the following:

• Systemic therapy, including but not limited to: >2 months of ADT; >2 months of conventional hormonal therapy (e.g., flutamide, bicalutamide); next-generation hormonal agents (e.g., darolutamide, abiraterone, apalutamide, enzalutamide, relugolix); chemotherapy (e.g., docetaxel); immunotherapy; targeted therapy;
• Local radiotherapy;
• Planned bilateral orchiectomy during the study treatment period;
• Inability to tolerate darolutamide or ADT;
• Concurrent participation in, or planned participation in, another clinical trial;
• A malignancy other than prostate cancer within the past 5 years or concurrently, except for cured basal cell carcinoma of the skin;
• Any concomitant disease or condition that, in the investigator's judgment, presents a serious risk to patient safety, may confound study results, or may interfere with completion of the study (e.g., severe cardiovascular disease, active infection, gastrointestinal disease, neurologic or psychiatric disorders, etc.);
• Any other condition deemed by the investigator to make the patient unsuitable for this study.