Immediate results of perineal implantation of a prostate-rectum biodegradable spacer

Aim. To evaluate the immediate results of perineal implantation of a biodegradable spacer based on stabilized hyaluronic acid (SНA) of non-animal origin as a way to optimize radiation treatment of prostate cancer.

Materials and methods. The study included 48 patients with verified low and intermediate risk prostate cancer per NCCN (National Comprehensive Cancer Network) who received five-fraction stereotactic radiotherapy as radical treatment. Prior to radiotherapy, all patients underwent insertion of a prostate-rectum biodegradable spacer (PRBS) based on synthetic SHA in the volume of 4–8 mL.

Results. There were no allergic and inflammatory reactions of tissues to the chemical composition of the implanted PRBS. Despite the invasive nature of the procedure, we did not observe any cases of infectious complications.

SНA used in the study demonstrated high levels of hydration (swelling) equal to 24.4 ± 1.5 (20.7–27.3) %, as well as temporal and spatial stability, which determined its optimal characteristics for use as a radiotherapeutic spacer. In all 48 patients, the projected distance (≥1 cm) between the prostate gland and the anterior wall of the rectum was achieved before the start of irradiation. The administration of 4 mL of SНA made it possible to achieve optimal symmetry of the formed space only in one (16.7 %) patient. An increase in the implant volume of the polymer to 6 mL increased the number of such cases to 28.6 %, and after injection of 8 mL it increased to 57 %.

The use of PRBS made it possible to reduce radiation dose to the rectum from 21.5 % (D_0.1cc (dose per 0.1 cm³ of rectum)) (р <0.0001) to 92.8 % (V_{75 %} (volume receiving 75 % or more of the prescribed dose)) (р <0.0001). Dose reduction for one of the most clinically validated parameters – D_2cc (dose to 2 cm³ of rectum)) was 31.5 % (р <0.0001) on average.

Conclusion. Perineal implantation of a non-animal SНA (Russia) as a radiotherapy spacer in patients with prostate cancer demonstrates excellent safety and efficacy profiles.

1. Mariados N., Sylvester J., Shah D. et al. Hydrogel spacer prospective multicenter randomized controlled pivotal trial: dosimetric and clinical effects of perirectal spacer application in men undergoing prostate image guided intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys 2015;92(5):971–7. DOI: 10.1016/j.ijrobp.2015.04.030

2. Karsh L.I., Gross E.T., Pieczonka C.M. et al. Absorbable hydrogel spacer use in prostate radiotherapy: a comprehensive review of phase 3 clinical trial published data. Urology 2018;115(1):39–44. DOI: 10.1016/j.urology.2017.11.016

3. Mariados N.F., Orio P.F. 3rd, Schiffman Z. et al. Hyaluronic acid spacer for hypofractionated prostate radiation therapy: a randomized clinical trial. JAMA Oncol 2023;9(4):511–8. DOI: 10.1001/jamaoncol.2022.7592

4. Schaeffer E.M., Srinivas S., Adra N. et al. Prostate Cancer, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2023;21(10):1067–96. DOI: 10.6004/jnccn.2023.0050

5. Biodegradable spacer insertion to reduce rectal toxicity during radiotherapy for prostate cancer Interventional procedures guidance [IPG752]. Published: 07 February 2023. Available at: www.nice.org.uk/guidance/ipg752/chapter/3-Committee-considerations

6. Hamstra D.A., Mariados N., Sylvester J. et al. Sexual quality of life following prostate intensity modulated radiation therapy (IMRT) with a rectal/prostate spacer: secondary analysis of a phase 3 trial. Pract Radiat Oncol 2018;8(1):7–15. DOI: 10.1016/j.prro.2017.07.008

7. Seymour Z.A., Pinkawa M., Daignault-Newton S. et al. A pooled long-term follow-up after radiotherapy for prostate cancer with and without a rectal hydrogel spacer: impact of hydrogel on decline in sexual quality of life. Front Oncol 2023;13:1239104. DOI: 10.3389/fonc.2023.1239104

8. Novikov S.N., Novikov R.V., Ilyn N.D. et al. The first experience of clinical application of an animal collagen-based spacer of domestic production to optimize the radiation treatment for prostate cancer: indications, technique and complications. Voprosy onkologii = Oncology Issues 2022;68(6):797–804. (In Russ.). DOI: 10.37469/0507-3758-2022-68-6-797-804

9. Novikov R.V., Zhivulina T.V., Sysoeva V.V. et al. Methodological aspects of implantation of a Russian prostate-rectum spacer based on stabilized hyaluronic acid of non-animal origin. Onkourologiya = Cancer Urology 2024;20(1):67–78. (In Russ.). DOI: 10.17650/1726-9776-2024-20-1-67-78

10. Grossman C.E., Folkert M.R., Lobaugh S. et al. Quality metric to assess adequacy of hydrogel rectal spacer placement for prostate radiation therapy and association of metric score with rectal toxicity outcomes. Adv Radiat Oncol 2023;8(4):101070. DOI: 10.1016/j.adro.2022.101070

11. Lukka H.R., Pugh S.L., Bruner D.W. et al. Patient reported outcomes in NRG oncology RTOG 0938, evaluating two ultrahypofractionated regimens for prostate cancer. Int J Radiat Oncol Biol Phys 2018;102(2):287–95. DOI: 10.1016/j.ijrobp.2018.06.008

12. Christensen L. Normal and pathologic tissue reactions to soft tissue gel fillers. Dermatol Surg 2007;33 Suppl 2:S168–75. DOI: 10.1111/j.1524-4725.2007.33357.x

13. Xiong C., Chen Y., Xu Y. et al. A review of complications of polyacrylamide hydrogel injection. C J Plast Rec Surg 2023;5(2):86–95. DOI: 10.1016/j.cjprs.2022.11.003

14. Harvey M., Ong W.L., Chao M. et al. Comprehensive review of the use of hydrogel spacers prior to radiation therapy for prostate cancer. BJU Int 2023;131(3):280–7. DOI: 10.1111/bju.15821

15. Fischer-Valuck B.W., Chundury A., Gay H. et al. Hydrogel spacer distribution within the perirectal space in patients undergoing radiotherapy for prostate cancer: impact of spacer symmetry on rectal dose reduction and the clinical consequences of hydrogel infiltration into the rectal wall. Pract Radiat Oncol 2017;7(3): 195–202. DOI: 10.1016/j.prro.2016.10.004

16. Shamsesfandabadi P., Ponnapalli S., Spencer K. et al. CT vs. MRI: which is more accurate in grading rectal wall infiltration after hydrogel spacer placement for prostate cancer patients? Int J Radiat Oncol Biol Phys 2023;117(2):e436–7. DOI: 10.1016/j.ijrobp.2023.06.1608

17. McLaughlin M.F., Folkert M.R., Timmerman R.D. et al. Hydrogel spacer rectal wall infiltration associated with severe rectal injury and related complications after dose intensified prostate cancer stereotactic ablative radiation therapy. Adv Radiat Oncol 2021;6(4):100713. DOI: 10.1016/j.adro.2021.100713

18. Kojima K., Takahashi Y., Sugiyama S. et al. A case of migration of a hydrogel spacer for radiotherapy into the pulmonary artery. Acta Med Okayama 2023;77(6):647–50. DOI: 10.18926/AMO/66157

19. Morisaka H., Marino K. Hydrogel spacer migration into periprostatic venous plexus. AJR Am J Roentgenol 2022;218(4):757. DOI: 10.2214/AJR.21.27049

20. Qiao Y., Patel S., Burney I. et al. A case report: retrograde arterial embolization of locally-injected SpaceOAR hydrogel material into the right common iliac artery bifurcation. Radiol Case Rep 2023;18(2):719–26. DOI: 10.1016/j.radcr.2022.02.042

21. Müller A.C., Mischinger J., Klotz T., Gagel B. et al. Interdisciplinary consensus statement on indication and application of a hydrogel spacer for prostate radiotherapy based on experience in more than 250 patients. Radiol Oncol 2016;50(3):329–36. DOI: 10.1515/raon-2016-0036

22. Hwang M.E., Black P.J., Elliston C.D. et al. A novel model to correlate hydrogel spacer placement, perirectal space creation, and rectum dosimetry in prostate stereotactic body radiotherapy. Radiat Oncol 2018;13(1):192. DOI: 10.1186/s13014-018-1135-6

23. Liu H., Borden L., Wiant D. et al. Proposed hydrogel-implant quality score and a matched-pair study for prostate radiation therapy. Pract Radiat Oncol 2020;10(3):202–8. DOI: 10.1016/j.prro.2020.02.006

24. Giacometti V., McLaughlin O., Comiskey P. et al. Validation of a quality metric score to assess the placement of hydrogel rectal spacer in patients treated with prostate stereotactic radiation therapy. Adv Radiat Oncol 2024;9(3):101396. DOI: 10.1016/j.adro.2023.101396

25. Pinkawa M., Klotz J., Djukic V. et al. Learning curve in the application of a hydrogel spacer to protect the rectal wall during radiotherapy of localized prostate cancer. Urology 2013;82(4):963–8. DOI: 10.1016/j.urology.2013.07.014

26. Narukawa T., Shiraishi T., Aibe N. et al. New modified technique of hydrogel spacer implantation for prostate cancer: a novel method for separation at the prostate apex level under real-time ultrasound guidance. J Med Ultrason (2001) 2022;49(4):751–2. DOI: 10.1007/s10396-022-01254-y

27. King M.T., Svatos M., Chell E.W. et al. Evaluating the quality-of-life effect of apical spacing with hyaluronic acid prior to hypofractionated prostate radiation therapy: a secondary analysis. Pract Radiat Oncol 2023:S1879-8500(23)00338-7. DOI: 10.1016/j.prro.2023.11.010

28. Svatos M., Chell E., Low D.A. et al. Symmetry, separation, and stability: Physical properties for effective dosimetric space with a stabilized hyaluronic acid spacer. Med Phys 2024;51(9):6231–45. DOI: 10.1002/mp.17292

29. Björeland U., Notstam K., Fransson P. et al. Hyaluronic acid spacer in prostate cancer radiotherapy: dosimetric effects, spacer stability and long-term toxicity and PRO in a phase II study. Radiat Oncol 2023;18(1):1. DOI: 10.1186/s13014-022-02197-x

30. Ogita M., Yamashita H., Nozawa Y. et al. Phase II study of stereotactic body radiotherapy with hydrogel spacer for prostate cancer: acute toxicity and propensity score-matched comparison. Radiat Oncol 2021;16(1):107. DOI: 10.1186/s13014-021-01834-1

31. Folkert M.R., Zelefsky M.J., Hannan R. et al. A multi-institutional phase 2 trial of high-dose SABR for prostate cancer using rectal spacer. Int J Radiat Oncol Biol Phys 2021;111(1):101–9. DOI: 10.1016/j.ijrobp.2021.03.025

32. Miller L.E., Efstathiou J.A., Bhattacharyya S.K. et al. Association of the placement of a perirectal hydrogel spacer with the clinical outcomes of men receiving radiotherapy for prostate cancer: a systematic review and meta-analysis. JAMA Netw Open 2020;3(6):e208221. DOI: 10.1001/jamanetworkopen.2020.8221

33. Song D.Y., Herfarth K.K., Uhl M. et al. A multi-institutional clinical trial of rectal dose reduction via injected polyethylene-glycol hydrogel during intensity modulated radiation therapy for prostate cancer: analysis of dosimetric outcomes. Int J Radiat Oncol Biol Phys 2013;87(1):81–7. DOI: 10.1016/j.ijrobp.2012.12.019