A Prospective Study Based on Spatial Multi-omics to Predict the Efficacy of ADT Combined With Second-generation Novel Hormonal Agents in Metastatic Hormone-sensitive Prostate Cancer.

A Prospective Study Based on Spatial Multi-Omics for Predicting the Efficacy of Androgen Deprivation Therapy Combined With Second-Generation Novel Endocrine Therapeutic Agents in Metastatic Hormone-Sensitive Prostate Cancer.

This study plans to enroll patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) and conduct a prospective, single-center, observational study. By performing whole-exome sequencing (WES), Xenium spatial transcriptomics, and PhenoCycler-Fusion spatial single-cell proteomics (PCF analysis) on tumor tissue samples, we aim to comprehensively delineate the molecular landscape of patients with different spatial multi-omic profiles in the real-world setting. We will investigate the associations between these molecular features and differential treatment responses to various therapeutic regimens, and further construct predictive models of treatment response. Ultimately, this will enable precise evaluation of treatment outcomes across distinct molecular subtypes and provide evidence to support individualized precision diagnostics and therapeutics for patients with mHSPC.

1、Baseline sample collection: Tumor tissues will be collected via prostate biopsy from enrolled patients. The specimens will be tripartite: one aliquot for standard histopathology, one for WES, and one for spatial multi-omic profiling (Xenium and PhenoCycler-Fusion).2、Follow-up: Patients will be assessed every 3 months during therapy, with CBC, biochemistry, sex hormones, and serum PSA. Prostate mpMRI will be repeated every 3 months. PSA testing frequency may be modified if PSA progression occurs. Follow-up continues until CRPC development or death.3、（1）Primary: Build a prognostic model integrating Xenium, WES, and PCF data.（2）Secondary: bPFS and OS.（3）Progression: PSA rise to ≥0.2 ng/mL confirmed on repeat testing after prior undetectable levels.

Inclusion Criteria:

1. Age > 18 years and < 85 years.
2. Histopathologically confirmed prostate adenocarcinoma, ductal adenocarcinoma, or intraductal carcinoma.
3. Imaging evidence of definite distant metastases (according to RECIST criteria).
4. Pre-biopsy PSA ≥ 20 ng/mL or Gleason score ≥ 4+4.
5. No prior hormonal therapy or other systemic anti-tumor regimens.
6. ECOG performance status 0-2, with an estimated life expectancy > 6 months.
7. Adequate organ function.h. Ability and willingness to provide written informed consent, and capability to comply with the study visit schedule.

Exclusion Criteria:

1. Histopathological diagnosis of neuroendocrine or small cell prostate cancer.
2. No definite distant metastases detected on imaging.
3. Prior history of anti-tumor therapy (including neoadjuvant, adjuvant, or other treatments).
4. Submitted biopsy samples fail to meet quality control requirements.
5. Concurrent severe endocrine or metabolic disorders, or other severe digestive system diseases.
6. Concurrent chronic hepatitis, cirrhosis, chronic nephritis, renal insufficiency, or other relevant conditions.
7. History of immunodeficiency or organ transplantation.
8. History of other concurrent malignancies.
9. Concurrent enrollment in other clinical trials.
10. Other conditions that the investigator deems unsuitable for study enrollment.