High-risk localized prostate cancer (PCa) poses a significant risk of recurrence and progression to a lethal phenotype. Neoadjuvant therapy followed by radical prostatectomy (RP) is being explored as a potential treatment option for these patients. Docetaxel, a chemotherapeutic agent, has shown efficacy in treating high-volume metastatic hormone-sensitive PCa and metastatic castration-resistant PCa, prompting investigations into its preoperative use for high-risk localized PCa.
Neoadjuvant chemohormonal therapy (NCHT) combines chemotherapy with hormonal therapy before surgery to reduce tumor burden and treat micrometastases. While traditional neoadjuvant hormonal therapy (NHT) has shown limited benefits, the addition of docetaxel to NHT has demonstrated improved oncological outcomes. However, this approach increases the rate of adverse events and economic burdens, emphasizing the need for careful patient selection.
Pathological response to NCHT, evaluated through changes in tumor volume and cellularity, serves as a crucial endpoint for assessing treatment efficacy. Studies have shown that patients with a favorable pathological response, such as minimal residual disease or pathological complete response, have better outcomes. Molecular imaging, specifically prostate-specific membrane antigen (PSMA) PET/CT, has emerged as a promising tool for evaluating the effectiveness of NCHT and predicting oncological outcomes.
Predictive biomarkers, including the expression status of androgen receptor (AR), AR-V7, Ki-67, PTEN, and TP53, play a significant role in identifying suitable candidates for NCHT. Additionally, genetic mutations in homologous recombination and mismatch repair genes may guide the selection of targeted therapies, such as PARP inhibitors and immunotherapy, in the neoadjuvant setting.
In conclusion, NCHT represents a promising neoadjuvant regimen for high-risk PCa, with the potential to improve survival outcomes. However, the selection of appropriate candidates and the evaluation of pathological response are essential for maximizing the benefits of this treatment approach. The integration of advanced imaging techniques and biomarker analysis will further enhance the precision and effectiveness of neoadjuvant therapy for prostate cancer.
