Efficacy of triplet therapy based on organoid drug sensitivity testing in lung metastatic hormone-sensitive prostate cancer.

Abstract

e17101 Background: Metastatic prostate cancer (mPC) is an advanced stage of prostate cancer, and the presence of visceral metastases in prostate cancer often suggests a worse prognosis. However, metastatic high-grade prostate cancer (mHSPC) lacks effective means to identify patients suitable for targeted therapies. Organoids are three-dimensional (3D) cell cultures derived from individual stem cells and cultivated in vitro. They are widely utilized as in vitro assays to predict the sensitivity of tumor cells to chemotherapeutic agents, thereby informing personalized treatment strategies. Methods: In the period between 2019 and 2024, a collection of prostate cancer patients admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University was undertaken, and their metastatic characteristics were subsequently screened and analysed. For HSPC patients with lung metastasis, prostate cancer tissues were collected and cultured into organoids after obtaining informed consent. Patients sensitive to docetaxel were identified through a drug sensitivity assay, and were administered a regimen comprising goserelin acetate extended-release microspheres in combination with rezvilutamide and docetaxel (6 cycles). The tumour remission of the patients was monitored via PSA and imaging examinations. Results: A total of 6,269 patients were included in this investigation. The most prevalent site of metastasis was bone, with 1,155 cases (18.40%), followed by visceral metastasis, including 213(3.40%) lung metastasis, 113(1. 80%) liver metastasis, 31(0.50%) adrenal metastasis, 31(0.49%) gastric metastasis, 20(0.32%) brain metastasis, 8(0.13%) peritoneal metastasis, 6(0.10%) kidney metastasis. After performing drug sensitivity testing, 15 HSPC patients with lung metastases were constructed prostate cancer organoids .Following the administration of triple therapy, a reduction in PSA to less than 0.2 ng/ml was observed in all 15 patients, and complete imaging remission was noted in 12 (80%) of them. Treatment-related adverse effects, including anaemia, arthralgia, peripheral oedema, diarrhoea, constipation and nausea, were mitigated through symptomatic treatment. No instances of grade 3 or higher adverse effects were observed, and no instances of delayed or interrupted treatment due to adverse effects were reported. Conclusions: The triple regimen of goserelin acetate extended-release microspheres in combination with rezvilutamide and docetaxel demonstrated encouraging outcomes in HSPC with lung metastasis. The construction of organoid and drug sensitivity assays holds great potential in facilitating more precise screening of suitable treatment regimens for individual patients.