FUNCTIONAL AND MORPHOMETRIC EVALUATION OF PROSTATE MICROCIRCULATION FOLLOWING HIGH-INTENSITY FOCUSED ULTRASOUND THERAPY WITH ANDROGEN DEPRIVATION FOR PROSTATIC ADENOCARCINOMA

Objective. To evaluate morphometric and hemodynamic changes in the prostate microcirculation under high-intensity focused ultrasound therapy (HIFU) combining with androgen deprivation in prostate cancer patients with a focus on the treatment effect assessment. Material and methods. 119 patients with localized adenocarcinoma of the prostate (Т2а-сN0M0) were examined prior to HIFU ablation and 3 to 36 months following the treatment. Microvascular density in the prostate tissue and hemodynamic parameters recorded by laser Doppler flowmetry at the prostate projection area (PPA) of the skin were analyzed comparatively. Results and discussion. Successful HIFU ablation (recurrence free survival at 3-year follow-up period) was associated with higher pretreatment microvascular density in the prostate tumor tissue and with a marked reduction of this parameter in the areas of residual non-neoplastic parenchyma after the ablation, which was accompanied by a significant decrease in PPA microhemodynamics. A course of androgen deprivation administered 1-3 months prior to ablation contributed to a moderate pre-HIFU reduction of tumor vascularization and PPA microcirculation index. As compared to HIFU monotherapy, cooperative use of HIFU and androgen blockade was associated with a relative decrease in the number of microvessels in the areas of residual neoplastic and non-neoplastic parenchyma in cases with local recurrence. A substantial increase of PPA microcirculation indices 6 or more months after HIFU ablation was found to be strongly associated with prostate cancer local recurrence which suggests that laser Doppler flowmetry could be used in the complex monitoring of the outcome from HIFU therapy for prostatic adenocarcinoma.

prostate cancer, high-intensity focused ultrasound, HIFU, androgen deprivation, microvascular density, laser Doppler flowmetry

1. Крянга А.А., Кулишова Т.В., Газаматов А.В. Косвенная оценка состояния микроциркуляции в предстательной железе у больных хроническим абактериальным простатитом в динамике на фоне комплексного сочетанного лечения // Лазер. медицина. 2016. 20. (4). 52-55.

2. Мерабишвили В.М., Петрова Н.Г., Атрощенко А.В., Харитонов М.В. Эпидемиология рака предстательной железы (популяционное исследование) // Вопр. онкологии. 2014. 60. (4). 458-464.

3. Неймарк А.И., Кондратьева Ю.С., Неймарк Б.А. Лазерная допплеровская флоуметрия при заболеваниях мочеполовой системы. М.: Практ. медицина, 2011. 104 с.

4. Неймарк А.И., Неймарк Б.А., Лушникова Е.Л., Бакарев М.А., Левин В.П., Ноздрачев Н.А., Тачалов М.А. Способ диагностики рецидивов рака предстательной железы у мужчин. Пат. 2658460 РФ; Опубл. 21.06.2018.

5. Неймарк А.И., Тарасова Т.С. Способ дифференциальной диагностики рака предстательной железы. Пат. 2361520 РФ; Опубл. 20.07.2009.

6. Неймарк А.И., Тачалов М.А., Неймарк Б.А. Адьювантная гормональная терапия у пациентов, перенесших HIFU-терапию по поводу локализованного рака предстательной железы // Онкоурология. 2014. (3). 69-72.

7. Фомкин Р.Н., Воронина Е.С., Попков В.М., Маслякова Г.Н., Блюмберг Б.И. Прогностическое значение молекулярно-биологических, морфологических и клинических маркеров в оценке эффективности лечения локализованного рака предстательной железы высокоинтенсивным сфокусированным ультразвуком // Эксперим. и клин. урология. 2013. (4). 29-33.

8. Aslan G., Cimen S., Yorukoglu K., Tuna B., Sonmez D., Mungan U., Celebi I. Vascular endothelial growth factor expression in untreated and androgen-deprived patients with prostate cancer // Pathol. Res. Pract. 2005. 201. (8-9). 593-598.

9. Biermann K., Montironi R., Lopez-Beltran A., Zhang S., Cheng L. Histopathological findings after treatment of prostate cancer using high-intensity focused ultrasound (HIFU) // Prostate. 2010. 70. (11). 1196-1200.

10. Chaussy C.G., Thuroff S. High-Intensity focused ultrasound for the treatment of prostate cancer: a review // J. Endourol. 2017. 31. (1). S30-37.

11. Colombel M., Filleur S., Fournier P., Merle C., Guglielmi J., Courtin A., Degeorges A., Serre C.M., Bouvier R., Clézardin P., Cabon F. Androgens repress the expression of the angiogenesis inhibitor thrombospondin-1 in normal and neoplastic prostate // Cancer Res. 2005. 65. (1). 300-308.

12. Godoy A., Watts A., Sotomayor P., Montecinos V.P., Huss W.J., Onate S.A., Smith G.J. Androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell // Endocrinology. 2008. 149. (6). 2959-2969.

13. Luczynska E., Gasinska A., Wilk W. Microvessel density and expression of vascular endothelial growth factor in clinically localized prostate cancer // Pol. J. Pathol. 2013. 64. (1). 33-38.

14. Miyata Y., Mitsunari K., Asai A., Takehara K., Mochizuki Y., Sakai H. Pathological significance and prognostic role of microvessel density, evaluated using CD31, CD34, and CD105 in prostate cancer patients after radical prostatectomy with neoadjuvant therapy // Prostate. 2015. 75. (1). 84-91.

15. Rubin M.A., Buyyounouski M., Bagiella E., Sharir S., Neugut A., Benson M., de la Taille A., Katz A.E., Olsson C.A., Ennis R.D. Microvessel density in prostate cancer: lack of association with tumor grade, pathologic stage and clinical outcome // Urology. 1999. 53. (3). 542-547.

16. Russo G., Mischi M., Scheepens W., de la Rosette J.J., Wijkstra H. Angiogenesis in prostate cancer: onset, progression and imaging // BJU Int. 2012. 110. 794-808.

17. Wu F., Chen W.Z., Bai J., Zou J.Z., Wang Z.L., Zhu H., Wang Z.B. Tumor vessel destruction resulting from high-intensity focused ultrasound in patients with solid malignancies // Ultrasound Med. Biol. 2002. 28. (4). 535-542.