Laser-induced hyperthermia in rat prostate cancer: Role of site of tumor implantation

Objectives. To investigate the importance of the site of tumor implantation on the treatment response to laser-induced hyperthermia (LIH) of rat prost ate cancer (PCa), because interventional manipulations of PCa have been rep orted to increase metastatic dissemination. Methods. Seven to nine days after either subcutaneous or orthotopic implant ation of MatLyLu cells, LIH (46.5 degrees C) was induced using pulsed irrad iations of a neodymium:yttrium-aluminum-garnet laser. Both local control an d distant metastases were evaluated. Plasma metalloproteinase 9 (MMP-9) was tested as a possible marker of PCa progression and LIH response. Results. Twelve days after LIH treatment of subcutaneous tumors, the volume s were reduced by 64% after 8 minutes of irradiation, 73% after 10 minutes, 81% after 15 minutes, and 91.1% after 20 minutes. In the orthotopic model, the corresponding tumor reductions were 44% after 10 minutes, 61% after 20 minutes, and 65% after 30 minutes. Lung metastases were observed in only 1 animal with subcutaneous tumors. In contrast, 86% of the orthotopic tumor- bearing animals treated for 30 minutes had lung metastases compared with 23 % of the untreated tumor-bearing rats. MMP-9 expression was detected in bot h orthotopic and subcutaneous tumor tissue and in the plasma of tumor-beari ng rats. The prostate tissue of healthy rats and subcutaneous tumor-bearing rats was devoid of MMP-9. The plasma levels of MMP-9 showed a trend toward direct correlation with local tumor control but no correlation with the in cidence of metastasis. Conclusions. These data emphasize the importance of the site of tumor impla ntation for evaluation of the efficacy of therapeutic interventions and may warrant further studies before widespread clinical application of LIH as m onotherapy. UROLOGY 56: 167-172, 2000. (C) 2000, Elsevier Science Inc.