Intraductal Carcinoma of the Prostate Is Associated With Improved Efficacy of Olaparib Combined With Novel Hormonal Therapy in Metastatic Castration‐Resistant Prostate Cancer
Qiyu Zhu, Ling Wang, Junru Chen, Xiuya Zhou, Zehua Tan, Jingjing Guo, Haoyang Liu, Ling Nie, Ni Chen, Pengfei Shen, Zhenhua Liu, Hao Zeng, Jinge ZhaoABSTRACT
Intraductal carcinoma of the prostate (IDC‐P) has been associated with increased homologous recombination deficiency (HRD). We evaluated the association between IDC‐P and the efficacy of olaparib plus novel hormonal therapy (NHT) in metastatic castration‐resistant prostate cancer (mCRPC) after progression on prior NHT. A total of 64 consecutive patients were analyzed, including 33 with IDC‐P and 31 with prostate adenocarcinoma (PAC). An external validation cohort of 36 patients from two additional centers was also included. Primary outcomes were progression‐free survival (PFS), while treatment‐change free survival (TFS), prostate‐specific antigen response, overall survival, and adverse events were additionally assessed. After a median follow‐up of 35.0 months, IDC‐P was associated with longer PFS and TFS than PAC (PFS, 6.2 vs. 3.0 months; TFS, 10.0 vs. 6.3 months; both p < 0.01). This association remained significant in patients with BRCA1/2 mutations and after multivariable adjustment for BRCA1/2 mutation status. In the validation cohort, IDC‐P status was associated with longer PFS (6.1 vs. 3.1 months, p = 0.02). In an independent cohort of 187 patients with prostate cancer, IDC‐P was associated with higher HRD scores than PAC in the BRCA1/2‐mutated subgroup, with a nonsignificant trend in the BRCA1/2‐wild‐type subgroup, suggesting a possible biological context for the observed outcome association. These findings suggest that IDC‐P may serve as a practical pathological biomarker associated with improved outcomes following PARP inhibitor‐based therapy in mCRPC, although further large‐scale prospective validation is warranted.