Intraductal Carcinoma Predicts Poor Response to Neoadjuvant Therapy in High-risk Prostate Cancer: A Retrospective Analysis of a Prospective Trial.

Background and objective: High-risk localized prostate cancer (PCa) patients may require neoadjuvant treatment (androgen deprivation therapy [ADT] plus abiraterone with or without taxane-based chemotherapy) before radical prostatectomy (RP). Intraductal carcinoma of the prostate (IDC) is an aggressive histological variant of prostate adenocarcinoma. This study aims to evaluate the association of IDC on biopsy with pathological response in such PCa patients. Methods: A retrospective analysis was conducted using the prospective trial data from 75 patients with high-risk localized/locally advanced PCa treated with 24 wk of neoadjuvant therapy comprising ADT and abiraterone, with or without taxane-based chemotherapy, followed by RP. Pathological responses, including pathological complete response (pCR), minimal residual disease (MRD), and adverse pathology outcomes (ypN1 or ≥ypT3b), were analyzed. Multivariable logistic regression identified the predictors of poor pathological response. Key findings and limitations: Among 75 patients, 35 (47%) had IDC on biopsy. Patients with IDC had worse pathological outcomes: 32 of 35 (91%) failed to achieve a favorable response (pCR or MRD) compared with 26 of 40 (65%) in those without IDC. IDC was also associated with higher rates of adverse pathology at RP, occurring in 27 of 35 patients (77%) versus nine of 40 patients (22%) without IDC. IDC independently predicted poor response (odds ratio 6.18, 95% confidence interval 1.16-32.8; p = 0.032) after adjusting for tumor volume, Gleason grade, and prostate-specific antigen (PSA). In contrast, cribriform (Crib) pattern at biopsy did not impact response significantly. Metastatic progression and survival data were unavailable. Conclusions and clinical implications: IDC, but not Crib, on biopsy predicts poor pathological response to neoadjuvant therapy (ADT plus abiraterone with or without taxane-based chemotherapy) in high-risk PCa after adjusting for tumor volume and PSA. An understanding of this treatment-resistant phenotype will improve PCa biology insights and guide novel therapeutic strategies. Patient summary: Intraductal carcinoma (IDC) is a more aggressive form of prostate cancer that does not respond well to treatment. In our study, we found that 91% of patients who had IDC detected in their biopsy before surgery did not show a good response to presurgery therapy.