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

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.