Радиационно-индуцированная эректильная дисфункция у больных раком предстательной железы: современный взгляд на патогенез

Истинные причины развития половых нарушений после лучевого лечения рака предстательной железы, среди которых центральную роль занимает эректильная дисфункция, до сих пор окончательно не выяснены. Число пациентов, которым в качестве радикальной терапии выполняются различные варианты лучевого воздействия, неуклонно растет, что делает рассматриваемый вопрос весьма актуальным. В обзоре представлены современные данные по наиболее изученным вероятным механизмам снижения статуса эректильной функции после лучевой терапии рака простаты.

рак предстательной железы, лучевая терапия, эректильная дисфункция, обзор

1. Tétreault-Laflamme A, Zilli T, Meissner A, et al. The Quadrella: a novel approach to analyzing optimal outcomes after permanent seed prostate brachytherapy. Radiother Oncol. 2014; 111(1): 110–3. https://doi.org/10.1016/j.radonc.2014.01.017.

2. McCabe MP, Sharlip ID, Atalla E, et al. Definitions of sexual dysfunctions in women and men: a consensus statement from the Fourth International Consultation on Sexual Medicine 2015. J Sex Med. 2016; 13(2): 135–43. https://doi.org/10.1016/j.jsxm.2015.12.019.

3. Wortel RC, Incrocci L, Mulhall JP. Reporting erectile function outcomes after radiation therapy for prostate cancer: challenges in data interpretation. J Sex Med. 2017; 14(10): 1260–9. https://doi.org/10.1016/j.jsxm.2017.08.005.

4. Gaither TW, Awad MA, Osterberg EC, et al. The natural history of erectile dysfunction after prostatic radiotherapy: a systematic review and meta-analysis. J Sex Med. 2017; 14(9): 1071–8. https://doi.org/10.1016/j.jsxm.2017.07.010.

5. Olsson CE, Alsadius D, Pettersson N, et al. Patient-reported sexual toxicity after radiation therapy in long-term prostate cancer survivors. Br J Cancer. 2015; 113(5): 802–8. https://doi.org/10.1038/bjc.2015.275.

6. Bazinet A, Zorn KC, Taussky D, et al. Favorable preservation of erectile function after prostate brachytherapy for localized prostate cancer. Brachytherapy. 2020; 19(2): 222–7. https://doi.org/10.1016/j.brachy.2019.11.003.

7. Wang Y, Liu T, Rossi PJ, et al. Influence of vascular comorbidities and race on erectile dysfunction after prostate cancer radiotherapy. J Sex Med. 2013; 10(8): 2108–14. https://doi.org/10.1111/jsm.12215.

8. Kushnir T, Gofrit ON, Elkayam R, et al. Impact of androgen deprivation therapy on sexual and hormonal function in patients receiving radiation therapy for prostate cancer. Isr Med Assoc J. 2016; 18(1): 49–53.

9. Son CH, Chennupati SK, Kunnavakkam R, Liauw SL. The impact of hormonal therapy on sexual quality of life in men receiving intensity modulated radiation therapy for prostate cancer. Pract Radiat Oncol. 2015; 5(3): e223–8. https://doi.org/10.1016/j.prro.2014.10.003.

10. Kamran SC, D’Amico AV. Radiation therapy for prostate cancer. Hematol Oncol Clin North Am. 2020; 34(1): 45–69. https://doi.org/10.1016/j.hoc.2019.08.017.

11. Bruner DW, Hunt D, Michalski JM, et al. Preliminary patientreported outcomes analysis of 3-dimensional radiation therapy versus intensity-modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group (RTOG) 0126 prostate cancer trial. Cancer. 2015; 121(14): 2422–30. https://doi.org/10.1002/cncr.29362.

12. Marina O, Warner J, Ye H, et al. An age-corrected matchedpair study of erectile function in patients treated with dose-escalated adaptive image-guided intensity-modulated radiation therapy vs. high-dose-rate brachytherapy for prostate cancer. Brachytherapy. 2014; 13(2): 163–8. https://doi.org/10.1016/j.brachy.2013.10.006.

13. Loi M, Wortel RC, Francolini G, Incrocci L. Sexual function in patients treated with stereotactic radiotherapy for prostate cancer: a systematic review of the current evidence. J Sex Med. 2019; 16(9): 1409–20. https://doi.org/10.1016/j.jsxm.2019.05.019.

14. Rasmusson E, Gunnlaugsson A, Wieslander E, et al. Erectile dysfunction and absorbed dose to penile base structures in a randomized trial comparing ultrahypofractionated and conventionally fractionated radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2020; 107(1): 143–51. https://doi.org/10.1016/j.ijrobp.2020.01.022.

15. Dean RC, Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am. 2005; 32(4): 379–95. https://doi.org/10.1016/j.ucl.2005.08.007.

16. Mahmood J, Shamah AA, Creed TM, et al. Radiation-induced erectile dysfunction: recent advances and future directions. Adv Radiat Oncol. 2016; 1(3): 161–9. https://doi.org/10.1016/j.adro.2016.05.003.

17. Venkatesulu BP, Mahadevan LS, Aliru ML, et al. Radiationinduced endothelial vascular injury: a review of possible mechanisms. JACC Basic Transl Sci. 2018; 3(4): 563–72. https://doi.org/10.1016/j.jacbts.2018.01.014.

18. Новиков Р.В., Пономарева О.И., Летинский С.С., Новиков С.Н. Анатомо-топографическое обоснование «сосудосохраняющей» лучевой терапии рака предстательной железы. Экспериментальная и клиническая урология. 2020; 2: 84–91. https://doi.org/10.29188/2222-8543-2020-12-2-84-91.

19. van der Wielen GJ, Mulhall JP, Incrocci L. Erectile dysfunction after radiotherapy for prostate cancer and radiation dose to the penile structures: a critical review. Radiother Oncol. 2007; 84(2): 107–13. https://doi.org/10.1016/j.radonc.2007.07.018.

20. Merrick GS, Butler WM, Wallner KE, et al. The importance of radiation doses to the penile bulb vs. crura in the development of postbrachytherapy erectile dysfunction. Int J Radiat Oncol Biol Phys. 2002; 54(4): 1055–62. https://doi.org/10.1016/S0360-3016(02)03031-6.

21. Selek U, Cheung R, Lii M, et al. Erectile dysfunction and radiation dose to penile base structures: a lack of correlation. Int J Radiat Oncol Biol Phys. 2004; 59(4): 1039–46. https://doi.org/10.1016/j.ijrobp.2003.12.028.

22. Wright JL, Newhouse JH, Laguna JL, et al. Localization of neurovascular bundles on pelvic ct and evaluation of radiation dose to structures putatively involved in erectile dysfunction after prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2004; 59(2): 426–35. https://doi.org/10.1016/j.ijrobp.2003.11.022.

23. Chasseray M, Dissaux G, Bourbonne V, et al. Dose to the penile bulb and individual patient anatomy are predictive of erectile dysfunction in men treated with125 I low dose rate brachytherapy for localized prostate cancer. Acta Oncol. 2019; 58(7): 1029–35. https://doi.org/10.1080/0284186X.2019.1574981.

24. Thor M, Olsson CE, Oh JH, et al. Radiation dose to the penile structures and patient-reported sexual dysfunction in long-term prostate cancer survivors. J Sex Med. 2015; 12(12): 2388–97. https://doi.org/10.1111/jsm.13031.

25. Mulhall J, Ahmed A, Parker M, Mohideen N. The hemodynamics of erectile dysfunction following external beam radiation for prostate cancer. J Sex Med. 2005; 2(3): 432–7. https://doi.org/10.1111/j.1743-6109.2005.20362.x.

26. Herwig R. Erectile dysfunction and caverno-venous leak disease. J Transl Sci. 2018; 4(1): 3–5. https://doi.org/10.15761/JTS.1000205.

27. Cui A, Xu L, Mu J, et al. The role of shear wave elastography on evaluation of the rigidity changes of corpus cavernosum penis in venogenic erectile dysfunction. Eur J Radiol. 2018; 103: 1–5. https://doi.org/10.1016/j.ejrad.2018.03.025.

28. Lee JY, Jung DC, Lee S, et al. Stiffness of the central corpus cavernosum on shear-wave elastography is inversely correlated with the penile rigidity score in patients with erectile dysfunction. World J Mens Health. 2021; 39(1): 123–30. https://doi.org/10.5534/wjmh.190094.

29. Goldstein I, Feldman MI, Deckers PJ, et al. Radiation-associated impotence. a clinical study of its mechanism. JAMA. 1984; 251(7): 903–10. https://doi.org/10.1001/jama.251.7.903.

30. Zelefsky MJ, Eid JF. Elucidating the etiology of erectile dysfunction after definitive therapy for prostatic cancer. Int J Radiat Oncol Biol Phys. 1998; 40(1): 129–33. https://doi.org/10.1016/S0360-3016(97)00554-3.

31. van der Wielen GJ, Vermeij M, de Jong BW, et al. Changes in the penile arteries of the rat after fractionated irradiation of the prostate: a pilot study. J Sex Med. 2009; 6(7): 1908–13. https://doi.org/10.1111/j.1743-6109.2009.01272.x.

32. Nolan MW, Marolf AJ, Ehrhart EJ, et al. Pudendal nerve and internal pudendal artery damage may contribute to radiation-induced erectile dysfunction. Int J Radiat Oncol Biol Phys. 2015; 91(4): 796–806. https://doi.org/10.1016/j.ijrobp.2014.12.025.

33. Повелица Э.А., Залуцкий И.В., Доста Н.И. и др. Анализ причин половых нарушений у больных раком предстательной железы после хирургического и комплексного лечения. Вопросы онкологии. 2017; 63(6): 933–41.

34. Spratt DE, Lee JY, Dess RT, et al. Vessel-sparing radiotherapy for localized prostate cancer to preserve erectile function: a single-arm phase 2 trial. Eur Urol. 2017; 72(4): 617–24. https://doi.org/10.1016/j.eururo.2017.02.007.

35. Samlali H, Udrescu C, Lapierre A, et al. Prospective evaluation of a specific technique of sexual function preservation in external beam radiotherapy for prostate cancer. Br J Radiol. 2017; 90(1078): 20160877. https://doi.org/10.1259/bjr.20160877.

36. Mulhall JP, Yonover PM. Correlation of radiation dose and impotence risk after three-dimensional conformal radiotherapy for prostate cancer. Urology. 2001; 58(5): 828. https://doi.org/10.1016/s0090-4295(01)01415-7.

37. Gay HA, Barthold HJ, O’Meara E, et al. Pelvic normal tissue contouring guidelines for radiation therapy: a radiation therapy oncology group consensus panel atlas. Int J Radiat Oncol Biol Phys. 2012; 83(3): 353–62. https://doi.org/10.1016/j.ijrobp.2012.01.023.

38. Roach M 3rd, Nam J, Gagliardi G, et al. Radiation dose-volume effects and the penile bulb. Int J Radiat Oncol Biol Phys. 2010; 76(3): 130–4. https://doi.org/10.1016/j.ijrobp.2009.04.094.

39. Mangar SA, Sydes MR, Tucker HL, et al. Evaluating the relationship between erectile dysfunction and dose received by the penile bulb: using data from a randomised controlled trial of conformal radiotherapy in prostate cancer (MRC RT01, ISRCTN47772397). Radiother Oncol. 2006; 80(3): 355–62. https://doi.org/10.1016/j.radonc.2006.07.037.

40. Tøndel H, Lund JÅ, Lydersen S, et al. Dose to penile bulb is not associated with erectile dysfunction 18 months post radiotherapy: a secondary analysis of a randomized trial. Clin Transl Radiat Oncol. 2018; 29(13): 50–6. https://doi.org/10.1016/j.ctro.2018.09.006.

41. Böckelmann F, Hammon M, Lettmaier S, et al. Penile bulb sparing in prostate cancer radiotherapy: dose analysis of an in-house MRI system to improve contouring. Strahlenther Onkol. 2019; 195(2): 153–63. https://doi.org/10.1007/s00066-018-1377-0.

42. Magli A, Giangreco M, Crespi M, et al. Erectile dysfunction after prostate three-dimensional conformal radiation therapy. Correlation with the dose to the penile bulb. Strahlenther Onkol. 2012; 188(11): 997–1002. https://doi.org/10.1007/s00066-012-0227-8.

43. Murray J, Gulliford S, Griffin C, et al. Evaluation of erectile potency and radiation dose to the penile bulb using image guided radiotherapy in the CHHiP Trial. Clin Transl Radiat Oncol. 2020; 21(1): 77–84. https://doi.org/10.1016/j.ctro.2019.12.006.

44. DiBiase SJ, Wallner K, Tralins K, Sutlief S. Brachytherapy radiation doses to the neurovascular bundles. Int J Radiat Oncol Biol Phys. 2000; 46(5): 1301–7. https://doi.org/10.1016/s0360-3016(99)00551-9.

45. Ramirez-Fort MK, Rogers MJ, Santiago R, et al. Prostatic irradiation-induced sexual dysfunction: a review and multidisciplinary guide to management in the radical radiotherapy era (Part I defining the organ at risk for sexual toxicities). Rep Pract Oncol Radiother. 2020; 25(3): 367–75. https://doi.org/10.1016/j.rpor.2020.03.007.

46. Solan AN, Cesaretti JA, Stone NN, Stock RG. There is no correlation between erectile dysfunction and dose to penile bulb and neurovascular bundles following real-time low-doserate prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2009. 73(5): 1468–74. https://doi.org/10.1016/j.ijrobp.2008.06.1946.

47. Roach D, Holloway LC, Jameson MG, et al. Multi-observer contouring of male pelvic anatomy: highly variable agreement across conventional and emerging structures of interest. J Med Imaging Radiat Oncol. 2019; 63(2): 264–71. https://doi.org/10.1111/1754-9485.12844.

48. Giuliano F, Rowland DL. Standard operating procedures for neurophysiologic assessment of male sexual dysfunction. J Sex Med. 2013; 10(5): 1205–11. https://doi.org/10.1111/jsm.12164.

49. Clavell-Hernandez J, Ermeç B, Kadıoğlu A, Wang R. Perplexity of penile rehabilitation following radical prostatectomy. Turk J Urol. 2019; 45(2): 77–82. https://doi.org/10.5152/tud.2019.18488.

50. Doherty W, Bridge P. A systematic review of the role of penile rehabilitation in prostate cancer patients receiving radiotherapy and androgen deprivation therapy. J Med Imaging Radiat Sci. 2019; 50(1): 171–8. https://doi.org/10.1016/j.jmir.2018.09.004.

51. Zelefsky MJ, Shasha D, Branco RD, et al. Prophylactic sildenafil citrate improves select aspects of sexual function in men treated with radiotherapy for prostate cancer. J Urol. 2014; 192(3): 868–74. https://doi.org/10.1016/j.juro.2014.02.097.

52. Kimura M, Yan H, Rabbani Z, et al. Radiation-induced erectile dysfunction using prostate-confined modern radiotherapy in a rat model. J Sex Med. 2011; 8(8): 2215–26. https://doi.org/10.1111/j.1743-6109.2011.02351.x.

53. Mahmood J, Connors CQ, Alexander AA, et al. Cavernous nerve injury by radiation therapy may potentiate erectile dysfunction in rats. Int J Radiat Oncol Biol Phys. 2017; 99(3): 680–8. https://doi.org/10.1016/j.ijrobp.2017.06.2449.

54. Ashcraft KA, Hannan JL, Eichenbaum G, et al. Clarifying the relative impacts of vascular and nerve injury that culminate in erectile dysfunction in a pilot study using a rat model of prostate irradiation and a thrombopoietin mimetic. Int J Radiat Oncol Biol Phys. 2019; 103(5): 1212–20. https://doi.org/10.1016/j.ijrobp.2018.11.064.

55. Leiker AJ, Rezaeian NH, Laine AM, et al. Prostate cancer neurovascular element sparing with stereotactic ablative radiation therapy (SAbR): a pilot dosimetric study for the POTEN-C Trial. Int J Radiat Oncol Biol Phys. 2018; 102(3): e125. https://doi.org/10.1016/j.ijrobp.2018.07.335.