Active surveillance strategy after robot-assisted radical prostatectomy in patients with positive surgical margins: analysis of oncological outcomes and risk factors for biochemical recurrence

Introduction. Positive surgical margins (PSM) are identified in 10–46% of patients after radical prostatectomy (RP) and are a known risk factor for biochemical recurrence (BCR), creating a clinical dilemma between immediate adjuvant radiotherapy (ART) and active surveillance (AS) with the option of delayed salvage radiotherapy (SRT).

Objective. To assess the oncological safety of active surveillance in patients with PSM after robot-assisted radical prostatectomy (RARP) and to identify independent predictors of biochemical recurrence.

Materials & methods. We conducted a single-centre retrospective cohort study including 126 patients who underwent RARP for localised prostate cancer (cT1 – 2N0M0). Patients receiving neoadjuvant therapy were excluded from the analysis. In the PSM group (n = 33), postoperative management consisted of active surveillance. Biochemical recurrence was defined as two consecutive prostate-specific antigen (PSA) measurements ³ 0.2 ng/mL. Kaplan–Meier analysis, the log-rank test, and multivariable Cox regression were used for statistical evaluation.

Results. The median follow-up was 62.2 months. PSM were present in 33 (26.2%) patients. Five-year recurrencefree survival (RFS) was significantly lower in the PSM group than in patients with negative margins (p < 0.05). On multivariable analysis, high ISUP grade (4 – 5) (hazard ratio (HR) 5.82; 95% confidence interval (CI) 2.25 – 15.05; p < 0.05) and the presence of PSM (HR 5.11; 95% CI 2.25 – 11.63; p < 0.05) emerged as independent predictors of BCR. Among the 33 patients with PSM managed with AS, 15 (45.5%) developed BCR, of whom 12 (80.0%) subsequently received salvage therapy. Thus, over the entire follow-up period, 21 (63.6%) patients with PSM did not require any additional treatment.

Conclusion. Active surveillance in patients with PSM after RARP appears oncologically safe in the absence of highrisk features, allowing more than half of such patients to avoid unnecessary adjuvant radiotherapy. The decision to administer ART should be individualised and based on comprehensive risk assessment, with ISUP grade and margin status as key components.

1. Culp MB, Soerjomataram I, Efstathiou JA, Bray F, Jemal A. Recent Global Patterns in Prostate Cancer Incidence and Mortality Rates. Eur Urol. 2020;77(1):38-52. DOI: 10.1016/j.eururo.2019.08.005

2. Xu MY, Zeng N, Ma S, Hua ZJ, Zhang SH, Xiang JC, Xiong YF, Xia ZY, Sun JX, Liu CQ, Xu JZ, An Y, Wang SG, Xia QD. A clinical evaluation of robotic-assisted radical prostatectomy (RARP) in located prostate cancer: A systematic review and network meta-analysis. Crit Rev Oncol Hematol. 2024;204:104514. DOI: 10.1016/j.critrevonc.2024.104514

3. Zhang L, Zhao H, Wu B, Zha Z, Yuan J, Feng Y. Predictive Factors for Positive Surgical Margins in Patients With Prostate Cancer After Radical Prostatectomy: A Systematic Review and Meta-Analysis. Front Oncol. 2021;10:539592. DOI: 10.3389/fonc.2020.539592

4. Guo H, Zhang L, Shao Y, An K, Hu C, Liang X, Wang D. The impact of positive surgical margin parameters and pathological stage on biochemical recurrence after radical prostatectomy: A systematic review and meta-analysis. PLoS One. 2024;19(7):e0301653. DOI: 10.1371/journal.pone.0301653

5. Preisser F, Coxilha G, Heinze A, Oh S, Chun FK, Sauter G, Pompe RS, Huland H, Graefen M, Tilki D. Impact of positive surgical margin length and Gleason grade at the margin on biochemical recurrence in patients with organ-confined prostate cancer. Prostate. 2019;79(16):1832-1836. DOI: 10.1002/pros.23908

6. Carbonell E, Matheu R, Muní M, Sureda J, García-Sorroche M, Ribal MJ, Alcaraz A, Vilaseca A. The Effect of Adverse Surgical Margins on the Risk of Biochemical Recurrence after Robotic-Assisted Radical Prostatectomy. Biomedicines. 2022;10(8):1911. DOI: 10.3390/biomedicines10081911

7. Martini A, Gandaglia G, Fossati N, Scuderi S, Bravi CA, Mazzone E, Stabile A, Scarcella S, Robesti D, Barletta F, Cucchiara V, Mirone V, Montorsi F, Briganti A. Defining Clinically Meaningful Positive Surgical Margins in Patients Undergoing Radical Prostatectomy for Localised Prostate Cancer. Eur Urol Oncol. 2021;4(1):42-48. DOI: 10.1016/j.euo.2019.03.006

8. Beckmann KR, Vincent AD, O’Callaghan ME, Cohen P, Chang S, Borg M, Evans SM, Roder DM, Moretti KL; South Australia Prostate Cancer Clinical Outcomes Collaborative. Oncological outcomes in an Australian cohort according to the new prostate cancer grading groupings. BMC Cancer. 2017;17(1):537. DOI: 10.1186/s12885-017-3533-9

9. Mottet N, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, Fanti S, Fossati N, Gandaglia G, Gillessen S, Grivas N, Grummet J, Henry AM, van der Kwast TH, Lam TB, Lardas M, Liew M, Mason MD, Moris L, Oprea-Lager DE, van der Poel HG, Rouvière O, Schoots IG, Tilki D, Wiegel T, Willemse PM, Cornford P. EAUEANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer-2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2021;79(2):243-262. DOI: 10.1016/j.eururo.2020.09.042

10. Yang CW, Wang HH, Hassouna MF, Chand M, Huang WJS, Chung HJ. Prediction of a positive surgical margin and biochemical recurrence after robot-assisted radical prostatectomy. Sci Rep. 2021;11(1):14329. DOI: 10.1038/s41598-021-93860-y

11. Vale CL, Fisher D, Kneebone A, Parker C, Pearse M, Richaud P, Sargos P, Sydes MR, Brawley C, Brihoum M, Brown C, Chabaud S, Cook A, Forcat S, Fraser-Browne C, Latorzeff I, Parmar MKB, Tierney JF; ARTISTIC Metaanalysis Group. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data. Lancet. 2020;396(10260):1422-1431. DOI: 10.1016/S0140-6736(20)31952-8

12. Parker CC, Clarke NW, Cook AD, Kynaston HG, Petersen PM, Catton C, Cross W, Logue J, Parulekar W, Payne H, Persad R, Pickering H, Saad F, Anderson J, Bahl A, Bottomley D, Brasso K, Chahal R, Cooke PW, Eddy B, Gibbs S, Goh C, Gujral S, Heath C, Henderson A, Jaganathan R, Jakobsen H, James ND, Kanaga Sundaram S, Lees K, Lester J, Lindberg H, Money-Kyrle J, Morris S, O’Sullivan J, Ostler P, Owen L, Patel P, Pope A, Popert R, Raman R, Røder MA, Sayers I, Simms M, Wilson J, Zarkar A, Parmar MKB, Sydes MR. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. Lancet. 2020;396(10260):1413-1421. DOI: 10.1016/S0140-6736(20)31553-1

13. Kneebone A, Fraser-Browne C, Duchesne GM, Fisher R, Frydenberg M, Herschtal A, Williams SG, Brown C, Delprado W, Haworth A, Joseph DJ, Martin JM, Matthews JHL, Millar JL, Sidhom M, Spry N, Tang CI, Turner S, Wiltshire KL, Woo HH, Davis ID, Lim TS, Pearse M. Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, noninferiority trial. Lancet Oncol. 2020;21(10):1331-1340. DOI: 10.1016/S1470-2045(20)30456-3

14. Sargos P, Chabaud S, Latorzeff I, Magné N, Benyoucef A, Supiot S, Pasquier D, Abdiche MS, Gilliot O, Graff-Cailleaud P, Silva M, Bergerot P, Baumann P, Belkacemi Y, Azria D, Brihoum M, Soulié M, Richaud P. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol. 2020;21(10):1341-1352. DOI: 10.1016/S1470-2045(20)30454-X

15. James C, Brunckhorst O, Eymech O, Stewart R, Dasgupta P, Ahmed K. Fear of cancer recurrence and PSA anxiety in patients with prostate cancer: a systematic review. Support Care Cancer. 2022;30(7):5577- 5589. DOI: 10.1007/s00520-022-06876-z

16. Hollemans E, Verhoef EI, Bangma CH, Rietbergen J, Helleman J, Roobol MJ, van Leenders GJLH. Prostate Carcinoma Grade and Length But Not Cribriform Architecture at Positive Surgical Margins Are Predictive for Biochemical Recurrence After Radical Prostatectomy. Am J Surg Pathol. 2020;44(2):191-197. DOI: 10.1097/PAS.0000000000001384

17. Zaffuto E, Gandaglia G, Fossati N, Dell’Oglio P, Moschini M, Cucchiara V, Suardi N, Mirone V, Bandini M, Shariat SF, Karakiewicz PI, Montorsi F, Briganti A. Early Postoperative Radiotherapy is Associated with Worse Functional Outcomes in Patients with Prostate Cancer. J Urol. 2017;197(3 Pt 1):669-675. DOI: 10.1016/j.juro.2016.09.079