Yüksek Riskli Metastatik Olmayan Prostat Kanserinde Neoadjuvan Dosetaksel Tedavisinin Etkinliği

Abstract

Prostate cancer (PCa) is a disease that presents challenges in treatment selection due to its broad spectrum. Currently the treatment protocol for high-risk PCa patients remains unclear. International guidelines recommend combining local therapy with systemic therapy, however, it is not clear which local or systemic therapy should be chosen. Docetaxel chemotherapy, known for its efficacy in metastatic patients, is also considered potentially effective in this patient group. This study evaluated the combination of neoadjuvant docetaxel chemotherapy with androgen deprivation therapy in patients classified as high-risk and locally advanced according to the D’Amico risk classification. Among 1701 prostate cancer patients diagnosed and treated with retropubic radical prostatectomy or robot-assisted radical prostatectomy between 2000 and 2023 at Hacettepe University Faculty of Medicine, Department of Urology, 107 non-metastatic patients categorized as high-risk according to the D’Amico risk classification (PSA >20 ng/mL or ISUP grade 4-5 or clinical T2c-4 or N+) were included in the study. Patients received neoadjuvant chemohormonal therapy (75 mg/m² Docetaxel every 3 weeks, 22.5 mg Leuprolide every 3 months) followed by surgical treatment (multimodal therapy group) or surgical treatment without neoadjuvant therapy (monotherapy group). Various parameters such as biochemical recurrence-free survival, overall survival, metastasis-free survival, tumor downstaging, continence, and erectile functional outcomes were compared between the groups. Of the 172 patients, 35 received neoadjuvant therapy, and 72 underwent surgical treatment only. The median follow-up period was 34.5 (4-140) months. Biochemical recurrence occurred in 15 (44.1%) patients in the multimodal therapy group and 28 (40.6%) in the monotherapy group. The 5-year biochemical recurrence-free survival rates were 45.4 ± 8.3% for the monotherapy group and 41.9 ± 12.1% for the multimodal therapy group (HR: 0.79, 95% CI: 0.41-1.52, p=0.494). Among patients with lymph node involvement, the 2-year biochemical recurrence-free survival rate was 63.0 ± 12.3% in the multimodal therapy group and 20.0 ± 17.9% in the monotherapy group (HR: 0.16, 95% CI: 0.03-0.74, p=0.019). Grade 3 and 4 adverse effects, according to the Common Terminology Criteria for Adverse Events (CTCAE), were observed in 8 (22.8%) patients in the multimodal therapy group. There were no treatment-related deaths or secondary cancer developments. In the multimodal therapy group, 5 (14.2%) patients experienced grade 2 complications, and 3 (8.5%) had grade 3 complications according to the Clavien-Dindo classification. In the monotherapy group, 3 (4.1%) patients experienced grade 2 complications, 1 (1.4%) had grade 3, and 1 (1.4%) had grade 4 complications. No significant difference in surgical complications was found between the patient groups (p=0.245). The findings supported that neoadjuvant chemohormonal therapy could be safely used in high-risk PCa patients without increasing surgical complications and with tolerable adverse effect rates, extending biochemical recurrence-free survival in high-risk PCa patients with lymph node invasion. However, neoadjuvant therapy did not provide an advantage in terms of overall survival and metastasis-free survival.