Systemic Therapy Combined With Cytoreductive Prostatectomy for the Treatment of de Novo Poly-metastatic Hormone Sensitive Prostate Cancer: A Prospective, Open-label Randomized Controlled Trial

1. Subject Management

1. Recruitment of subjects The subjects are recruited from the outpatient clinic of the Department of Urology of Renji Hospital, Shanghai Jiao Tong University School of Medicine; the specific time was from the beginning of the recruitment of subjects to the end of reaching the target of the recruitment of subjects. If the attending physician's initial judgment meets the criteria for NAC, recruitment will be carried out after communicating with the patient and his/her family.
2. Informed consent process After the attending physician (investigator) finds patients who initially meet the enrollment criteria of this trial, he/she should give a written and verbal explanation to the subjects about the background, nature, significance, steps, benefits, risks, compensation, injury compensation, and withdrawal of the study, and he/she must obtain an informed consent form signed by each subject (or subject's legal representative). The informed consent form is dated, and the informed consent form and its copy are kept separately by the investigator and the subject.
3. Checking the enrollment criteria As soon as possible after the preliminary identification of subjects, the attending physician and the investigator will check the enrollment criteria together, make a formal decision to recruit or not to recruit into the group and inform the subjects, and explain the reasons for not recruiting into the group in detail and record them.
4. Examination of medical history and records of combined medications During the initial screening and verification of the enrollment criteria, the attending physician will obtain the subject's past history, current medical history, personal history, as well as comorbid medications, and previous medications. If necessary, the history and co-medication records will be declared by the patient himself/herself or under the supervision of the attending physician while signing the informed consent form.
5. Assignment of screening number At the time of signing the informed consent, each patient is assigned a screening number, the rules for the preparation of the screening number are specified separately, and should ensure the principles of continuity, traceability and de-specialization.
6. Assignment of treatment/randomization group numbers Sequence generation: the data manager should use SAS statistical software (SAS Institute. Cary, NC, USA) to generate the allocation sequence in a stratified block randomization with block length set to 4. All subjects were randomly (1:1) assigned to trial and control groups. Factors for stratification included tumor stage (M1a/M1b/M1c) and baseline alkaline phosphatase level (greater/less than ULN). Randomized assignment sequences were performed using sequentially coded sequestration, and interventions should in principle be assigned as soon as possible after generation of the randomized assignment sequence. Sequences should not be accessed by anyone other than the restricted data manager prior to allocation of the intervention.

Implementation: Generation of the randomized allocation sequence and allocation of the intervention by the data manager, and the generation of the sequence and the allocation of the intervention should be performed by different managers; recruitment of subjects by the attending clinical physician (investigator). 7. Trial Adherence Management During the course of the trial, patients' adherence to the trial will be examined and documented by the supervising physician at each visit and as deemed necessary by the investigator. If necessary, subjects may be instructed to complete a medication diary, which will be checked by the supervising physician and the investigator at each visit. Adherence reports are submitted to the Ombudsman for review as deemed necessary.

2. Intervention Trial group: Systemic therapy plus cytoreductive prostatectomy Control group: Standard of care.

3. Efficacy measurement Efficacy measurements of the specified items and frequencies are performed according to the visit requirements, and the efficacy is observed and recognized strictly according to the criteria set out in the outcomes, and the investigators and evaluators should form an efficacy report and include it in the case report form. PET-CT and PSMA-PET/CT examinations were for the exploratory purpose of this study, so they could be performed on a voluntary basis at the subjects' own expense and with their fully informed consent. The performance or failure of the examination and its results should not affect the performance of other treatments, nor should it affect the performance of other visits and programs.