Abstract
Objective: To obtain complete prostatic cell death in the treatment of early stage prostate cancer by High Intensity Focused Ultrasound (HIFU) therapy, we use Degarelix (GnRH antagonist) twice simultaneously. Patients and Methods: The first Degarelix subcutaneous injection was made two weeks before HIFU therapy, and second Degarelix was applied two weeks after the HIFU therapy. No additional maintenance Degarelix was used. To confirm the apoptosis induced by Degarelix, specimens obtained by transurethral resection simultaneously on HIFU were stained with caspase 3 and TUNEL. PSA was monitored every three months after this combination therapy as long as two years. These PSA values were compared with those who previously treated with HIFU without Degarelix. Results: Nine T1cN0M0 prostate cancer patients were enrolled to “HIFU + Degarelix” therapy. Pre treatment mean PSA level was 6.11 ± 1.83 ng/ml (SD), and PSA 3 months after the treatment was 0.02 ± 0.02. These low PSA levels continued thereafter (0.16 ng/ml ± 0.19 at 24 months). The mean pretreatment PSA level of the 34 patients underwent HIFU without Degarelix was 11.07 ± 13.9 ng/ml, 3 months post HIFU was 1.68 ± 3.04, (2.80 ± 3.97 at 24 months). Caspase 3 and TUNEL were positive on the glandular cells in TUR specimens of “HIFU + Degarelix” patients, suggesting Degarelix induced apoptosis. Conclusion: Although the number of our patients was small, the results of “Short course Degarelix + HIFU” would be promising for better long-term outcome than HIFU mono-therapy.
Highlights
Prostate cancer is the most commonly diagnosed cancer in the developed countries [1]
Cryotherapy, radio-frequency ablation therapy and high intensity focused ultrasound therapy (HIFU) are utilized as less invasive therapy for prostate cancer [4], these modalities have not accepted as standard therapy, presumably because the results are not as effective as surgery or radiation therapy [5], and the morbidities of these less invasive methods are not negligible [6]
Nine patients treated with HIFU + Degarelix were enrolled, and post HIFU prostate specific antigen (PSA) values were compared with the results of 34 patients treated with HIFU only
Summary
Prostate cancer is the most commonly diagnosed cancer in the developed countries [1]. More than ten thousands of early stage prostate cancer patients had undergone HIFU in the world, HIFU does not have an appraisal as a standard therapy The reason of this low estimation is due to lack of excellent long term results and lack of established methods to obtain stable results as well. Recent study revealed that small number of prostatic cancer cells can acquire an apoptotic tolerance by epithelial to mesenchymal transition (EMT) mechanism [8]. Some of these non-apoptotic cells will progress to castration resistant prostate cancer after obtaining ability to cell multiplication even under a hormonally castrated condition [9]. We here report our trial to add HIFU therapy at the timing when many prostatic cells are induced apoptosis by the first hormonal use for early stage prostate cancer two weeks after the initial use of Degarelix, which can properly reduce testosterone to castrate level in a few days
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