Intraductal Carcinoma of the Prostate Is Associated With Improved Efficacy of Olaparib Combined With Novel Hormonal Therapy in Metastatic Castration‐Resistant Prostate Cancer

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.