Robot-assisted radical prostatectomy with intraoperative assessment of surgical margin (per the CELPM protocol)

Background. Decision on using nerve-sparing technique during robot-assisted radical prostatectomy (RARP) involves a compromise between oncological safety and preservation of erectile function affecting patients' quality of life. One of the approaches to decreasing oncological risks of nerve-sparing technique is intraoperative histological examination of the areas of the prostate neighboring the neurovascular bundle.

Aim. To evaluate the efficacy of express intraoperative histological examination of prostate regions adjacent to neurovascular bundle (CELPM protocol) during nerve-sparing RARP.

Materials and methods. Between March 2019 and October 2025 at the S.P. Botkin Moscow Multidisciplinary Scientific and Clinical Center of the Moscow Healthcare Department, nerve-sparing RARP with express histological examination of the lateral prostate margin was performed in 58 patients. All surgical interventions were performed using Si and Xi da Vinci models through transperitoneal access by two surgeons. Express and final histological examinations of all samples were performed at the Division of Pathological Anatomy of the Center. Presence of tumor tissue in the stained resection margin was considered a positive result of the examination.

Results. Mean time to CELPM was 35 minutes. Mean operative time was 190 min. Unilateral and bilateral preservation of the neurovascular bundle was performed in 22.4 and 77.6 % of cases, respectively. Risk of recurrence was intermediate in 17.2 % of cases and high in 72.4 %. of cases. Extraprostatic tumor extension per the final histological examination was observed in 22.4 % of patients. The CELPM protocol showed tumor tissue in the resection margin in 23 % of cases. Planned histological examination of secondarily resected neurovascular bundles confirmed tumor process in 10 of 11 cases (90.9 %). In 1 case, oncological process in secondarily resected tissue was not confirmed. Tumor tissue in the resection margin during planned histological examination of the gross specimen (prostate, seminal vesicles, parts of the distal urethra/bladder neck) was found in 9 (15.5 %) of 58 cases. It is important to note that in all cases it was found outside the scope of previous express histological examination.

Conclusion. The use of express histological examination technique (CELPM protocol) during nerve-sparing RARP allows to intraoperatively evaluate the status of resection margin which allows to resect the neurovascular bundles with tumor tissue during a single surgery decreasing the risk of early biochemical recurrence. This technique might extend the indications for nerve-sparing RARP, especially in patients with intermediate and high risk.

1. Afferi L., Moschini M., Baumeister P. et al. Trends in risk-group distribution and Pentafecta outcomes in patients treated with nerve-sparing, robot-assisted radical prostatectomy: a 10-year low-intermediate volume single-center experience. World J Urol 2021;39(2):389-7. DOI: 10.1007/s00345-020-03206-y

2. Walsh P.C., Donker P.J. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 1982;128(3):492-7. DOI: 10.1016/s0022-5347(17)53012-8

3. Nguyen L.N., Head L., Witiuk K. et al. The risks and benefits of cavernous neurovascular bundle sparing during radical prostatectomy: a systematic review and meta-analysis. J Urol 2017;198(4):760-9. DOI: 10.1016/j.juro.2017.02.3344

4. Schlomm T., Tennstedt P., Huxhold C. et al. Neurovascular structure-adjacent frozen-section examination (NeuroSAFE) increases nerve-sparing frequency and reduces positive surgical margins in open and robot-assisted laparoscopic radical prostatectomy: experience after 11,069 consecutive patients. Eur Urol 2012;62(2):333-40. DOI: 10.1016/j.eururo.2012.04.057

5. Sokolov E.A., Veliev E.I., Paklina O.V., Knyshinsky G.V. Intraoperative histological frozen-section examination of prostate regions adjacent to neurovascular bundle: initial implementation experience during roboticassisted radical prostatectomy. Vestnik sovremennoy klinicheskoy meditsiny = The Bulletin of Contemporary Clinical Medicine 2019;12(6):66-71. DOI: 10.20969/VSKM.2019.12(6).66-71

6. Beyer B., Schlomm T., Tennstedt P. et al. A feasible and timeefficient adaptation of NeuroSAFE for da Vinci robot-assisted radical prostatectomy. Eur Urol 2014;66(1):138-44. DOI: 10.1016/j.eururo.2013.12.01

7. Sokolov E.A., Veliev E.I., Veliev R.A. Current view on nerve-sparing radical prostatectomy. Onkourologiya = Cancer Urology 2019;15(3):17-27. (In Russ.) DOI: 10.17650/1726-9776-2019-15-3-17-27

8. Keller E.X., Bachofner J., Britschgi A.J. et al. Prognostic value of unifocal and multifocal positive surgical margins in a large series of robot-assisted radical prostatectomy for prostate cancer. World J Urol 2019;37(9):1837-44. DOI: 10.1007/s00345-018-2578-y

9. Pushkar D.Yu., Kolontarev K.B. Robot-assisted radical prostatectomy - functional result. Part II. Khirurgiya. Zhurnal im. N.I. Pirogova = Pirogov Russian Journal of Surgery 2019;(4):80-6. (In Russ.). DOI: 10.17116/hirurgia201904180

10. Dangle P.P., Shah K.K., Kaffenberger B., Patel V.R. The use of high resolution optical coherence tomography to evaluate robotic radical prostatectomy specimens. Int Braz J Urol 2009;35(3):344-53. DOI: 10.1590/s1677-55382009000300011

11. Porpiglia F., Checcucci E., Amparore D. et al. Three-dimensional elastic augmented-reality robot-assisted radical prostatectomy using hyperaccuracy three-dimensional reconstruction technology: a step further in the identification of capsular involvement. Eur Urol 2019;76(4):505-14. DOI: 10.1016/j.eururo.2019.03.037

12. Windisch O., Diana M., Tilki D. et al. Intraoperative technologies to assess margin status during radical prostatectomy - a narrative review. Prostate Cancer Prostatic Dis 2025;28(1):81-8. DOI: 10.1038/s41391-024-00868-2

13. Van der Slot M.A., den Bakker M.A., Tan T.S.C. et al. NeuroSAFE in radical prostatectomy increases the rate of nerve-sparing surgery without affecting oncological outcome. BJU Int 2022;130(5): 628-36. DOI: 10.1111/bju.15771

14. Kroon L.J., Remmers S., Busstra M.B. et al. Centralized prostatectomy with intraoperative NeuroSAFE margin assessment improves surgical margin control. Histopathology 2024;85(5): 760-8. DOI: 10.1111/his.15291

15. Noel J., Spencer N.H., Lodia S. et al. Neurovascular structure-adjacent frozen-section examination robotic-assisted radical prostatectomy: outcomes from 500 consecutive cases in the UK. J Robot Surg 2022;16(4):951-6. DOI: 10.1007/s11701-021-01324-2. Erratum in: J Robot Surg 2022;16(4):957. DOI: 10.1007/s11701-021-01337-x

16. Dinneen E., Almeida-Magana R., Al-Hammouri T. et al. Effect of NeuroSAFE-guided RARP versus standard RARP on erectile function and urinary continence in patients with localised prostate cancer (NeuroSAFE PROOF): a multicentre, patient-blinded, randomised, controlled phase 3 trial. Lancet Oncol 2025;26(4):447-58. DOI: 10.1016/S1470-2045(25)00091-9

17. Dinneen E., Haider A., Freeman A. et al. NeuroSAFE PROOF Randomised Controlled Feasibility Study: brief report of perioperative outcomes, histological concordance, and feasibility. Eur Urol 2020;78(3):476-8. DOI: 10.1016/j.eururo.2020.03.052

18. Ambrosini F., Preisser F., Tilki D. et al. Nerve-sparing radical prostatectomy using the neurovascular structure-adjacent frozen-section examination (NeuroSAFE): results after 20 years of experience. Prostate Cancer Prostatic Dis 2025;28(2):483-9. DOI: 10.1038/s41391-024-00851-x