Predictive factors associated with differential pathologic response to neoadjuvant chemohormonal therapy in high-risk localized prostate cancer

Abstract

Purpose: To explore the clinical parameters and molecular biomarkers that can predict differential pathologic response to neoadjuvant chemohormonal therapy (NCHT) in prostate cancer (CaP).

Methods: A total of 128 patients with primary high-risk localized CaP who had received NCHT followed by radical prostatectomy (RP) were included. Androgen receptor (AR), AR splice variant-7 (AR-V7) and Ki-67 staining were evaluated in prostate biopsy specimens by immunohistochemistry. The pathologic response to NCHT in whole mount RP specimens was measured based on the reduction degree of tumor volume and cellularity compared to the paired pretreatment needle biopsy, and divided into 5 tier grades (Grades 0-4). Patients with Grades 2 to 4 (the reduction degree more than 30%) were defined as having a favorable response. Logistic regression was performed to explore the predictive factors associated with a favorable pathologic response. The predictive accuracy was evaluated by receiver operating characteristic (ROC) curve and area under the ROC curve (AUC).

Results: Ninety-seven patients (75.78%) had a favorable response to NCHT. Logistic regression showed that the preoperative PSA level, low AR expression and high Ki-67 expression in biopsy specimens were associated with a favorable pathologic response (P < 0.05). Furthermore, the AUC of the preoperative PSA level, AR and Ki-67 were 0.625, 0.624 and 0.723, respectively. Subgroup analysis revealed that the rate of favorable pathologic response to NCHT was 88.5% in patients with AR^lowKi-67^high, which was higher than patients with AR^lowKi-67^low, AR^highKi-67^low, and AR^highKi-67^high (88.5% vs. 73.9%, 72.9%, and 70.9%, all P < 0.05).

Conclusions: A lower preoperative PSA level was an independent predictive factor for a favorable pathologic response. Moreover, the expression status of AR and Ki-67 in biopsy specimens were associated with differential pathologic response to NCHT, and AR low/Ki-67 high was also associated with favorable response but warrants further evaluation in this patient subgroup and future trial clinical trial design.

Keywords: AR; High-risk localized prostate cancer; Ki-67; Neoadjuvant chemohormonal therapy; Pathologic response.