Neoadjuvant hormonal therapy for low-risk prostate cancer induces biochemical recurrence after radical prostatectomy via increased lymphangiogenesis-related parameters

Abstract

Background: The effects of neoadjuvant hormonal therapy (NHT) on pathological features and lymphangiogenesis in patients with prostate cancer (PCa) for each pre-operative risk classification are unclear. Methods: To clarify the anti-cancer effects of NHT, we investigated 153 patients (non-NHT group = 80 and NHT group = 73) who underwent radical prostatectomy (RP) in Nagasaki University Hospital. Lymph vessel density and area (evaluated by D2-40-positive vessels), vascular endothelial growth factor (VEGF)-C and VEGF-D expressions, and biochemical recurrence (BCR)-free survival were compared between these two groups for each D'Amico risk classification (low = 33, intermediate = 58, high = 62 patients). Results: In low-risk PCa patients, the risks of lymph vessel invasion and BCR were significantly higher in the NHT group than in the non-NHT group (P = 0.040 and 0.022, respectively). Such significant difference was not seen in the intermediate- or high-risk PCa groups. Lymph vessel density of the peri-tumoral and intra-tumoral areas and the lymph vessel area were significantly higher (P < 0.001) in the NHT group than in the non-NHT group in low-risk PCa. In regard to the expression of VEGF-C or VEGF-D, significant difference was not detected in low-risk PCa. Conclusions: NHT stimulated cancer cell progression and BCR via up-regulation of lymphangiogenesis-related parameters in patients with low-risk PCa. Although VEGF-C and VEGF-D expressions were not changed by NHT, lymph vessel density and area were increased in low-risk PCa patients. We suggest that NHT for patients with low-risk PCa may have a high risk for BCR after RP.