Background: The aim of the study was to measure plasma levels of the vascular endothelial growth factors (VEGF) A and D in serially collected blood specimens from non-localized prostate cancer (PCa) subjects.

Methods: Plasma VEGF A and D levels were measured in two serial specimens 3-6 months apart in two groups of non-localized stage PCa patients. Group 1 was comprised of patients with biochemical relapse after localized PCa treatments and/or patients with clinically metastatic hormone-sensitive stage PCa prior to receiving hormonal therapy. Group 2 included patients failing hormonal therapy for non-localized hormone-sensitive stage PCa. VEGF A and D levels were compared within each cancer group between the two time-points using the Wilcoxon Rank Sum test.

Results: At the first time-point in Group 1 (n = 46), median VEGF-A and D levels were measured at 5.2 (pg/ml) (range = 0-97) and 319 (range = 172-780) (pg/ml). For Group 2 (n = 34) VEGF-A level was 9.6 pg/ml (range = 0-78) and VEGF-D level was 377 pg/ml (range = 243-989) for the first measurement. Median time-period for the serial second specimen was 189 days in Group 1 and 84 days in Group 2. At the second time-point, in Group 1, VEGF-A levels were 0.0 pg/ml (P = 0.0002) while VEGF-D increased to 349 pg/ml (P = 0.002). For Group 2 patients at the second time-point, median VEGF-A was 0.0 pg/ml (P = 1.0) and VEGF-D was measured at 442 pg/ml (P = 0.008).

Conclusions: Higher plasma VEGF-D than VEGF-A expression in advanced PCa stages suggests a greater role for VEGF-D dependent lymph angiogenesis in advanced stage PCa, which needs further evaluation.