Impact of peritoneal reconfiguration on lymphocele formation after robot-assisted radical prostatectomy with pelvic lymph node dissection: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT BACKGROUND Different strategies have been proposed to prevent lymphocele (LC) formation after radical prostatectomy (RARP) with pelvic lymph node dissection (PLND). According to

several recently published randomized control trials (RCTs) on the topic, peritoneal reconfiguration appears to be associated with promising results. This systematic review aimed to assess

the impact of peritoneal reconfiguration on LC formation in patients undergoing RARP and PLND. METHODS A comprehensive bibliographic search was conducted in August 2023. Studies assessing

patients with prostate cancer undergoing RARP with PLND (P) and concomitant peritoneal reconfiguration (I) compared or not with other techniques (C) to prevent LC formation (O) were

included. Original prospective and retrospective studies (S) were selected. LC and symptomatic LC rates were chosen as co-primary outcomes. Only RCTs were included in the meta-analysis.

RESULTS Eleven studies investigating 2991 patients were included in the systematic review, and five RCTs evaluating 1712 subjects were deemed eligible for meta-analysis. Peritoneal flap (PF)

was the most common surgical technique used for LC prevention (9 studies). A significantly lower likelihood of LC was observed after PF (OR 0.82, 95% CI 0.27–1.37, I2 = 74.54%), with no

significant difference in terms of symptomatic LC (OR 0.21, 95% CI −0.41–0.84, I2 = 0%). Probability of LC-related complications (OR 0.36, 95% CI 0.04–0.67, I2 = 0%), Clavien-Dindo ≥ 3

overall complications (OR 0.61, 95% CI 0.21–1.0, I2 = 0%), and Clavien-Dindo ≥ 3 LC-related complications (OR 0.98, 95% CI 0.29–1.67, I2 = 0%) were significantly lower after PF. CONCLUSIONS

PF after RARP with PLND reduces LC formation, LC-related complications, and severe postoperative adverse events. Access through your institution Buy or subscribe This is a preview of

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CHEMOHORMONAL THERAPY VS. EXTENDED PELVIC LYMPH-NODE DISSECTION IN HIGH-RISK PROSTATE CANCER TREATED WITH ROBOT-ASSISTED RADICAL PROSTATECTOMY Article Open access 01 March 2023 SIGNIFICANCE

OF PELVIC LYMPH NODE DISSECTION DURING RADICAL PROSTATECTOMY IN HIGH-RISK PROSTATE CANCER PATIENTS RECEIVING NEOADJUVANT CHEMOHORMONAL THERAPY Article Open access 11 June 2022 NEUROVASCULAR

STRUCTURE-ADJACENT FROZEN-SECTION EXAMINATION (NEUROSAFE) DURING ROBOT-ASSISTED RADICAL PROSTATECTOMY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF COMPARATIVE STUDIES Article 04 September 2024

DATA AVAILABILITY Sheets containing raw data (extracted variables, statistical analyses) are available upon request to the corresponding author. REFERENCES * Mottet N, Cornford P, Van den

Bergh R, Eberli D, De Meerleer G, De Santis M, et al. EAU Guidelines on Prostate Cancer. Edn presented at the EAU Annual Congress Milan. 2023. ISBN 978-94-92671-19-6 * Eastham JA, Auffenberg

GB, Barocas DA, Chou R, Crispino T, Davis JW, et al. Clinically Localized Prostate Cancer: AUA/ASTRO Guideline, Part II: Principles of Active Surveillance, Principles of Surgery, and

Follow-Up. J Urol. 2022;208:19–25. Article  PubMed  Google Scholar  * Fiori C, Checcucci E, Stura I, Amparore D, De Cillis S, Piana A, et al. Development of a novel nomogram to identify the

candidate to extended pelvic lymph node dissection in patients who underwent mpMRI and target biopsy only. Prostate Cancer Prostatic Dis. 2023;26:388–94. Article  PubMed  Google Scholar  *

Masterson J, Luu M, Naser-Tavakolian A, Freedland S, Sandler H, Zumsteg Z, et al. Concurrent prognostic utility of lymph node count and lymph node density for men with pathological

node-positive prostate cancer. Prostate Cancer Prostatic Dis. 2023. https://doi.org/10.1038/s41391-022-00635-1 * Creta M, Manfredi C, Arcaniolo D, Spirito L, Kaplan SA, Woo HH, et al.

Functional and oncological outcomes after radical prostatectomy in patients with history of surgery for lower urinary tract symptoms related to benign prostatic enlargement: A systematic

review with meta-analysis. Prostate Cancer Prostatic Dis. 2023. https://doi.org/10.1038/s41391-023-00678-y * Briganti A, Chun FKH, Salonia A, Suardi N, Gallina A, Da Pozzo LF, et al.

Complications and Other Surgical Outcomes Associated with Extended Pelvic Lymphadenectomy in Men with Localized Prostate Cancer. Eur Urol. 2006;50:1006–13. Article  PubMed  Google Scholar  *

Orvieto MA, Coelho RF, Chauhan S, Palmer KJ, Rocco B, Patel VR. Incidence of lymphoceles after robot-assisted pelvic lymph node dissection. BJU Int. 2011;108:1185–90. Article  PubMed 

Google Scholar  * Keskin MS, Argun ÖB, Öbek C, Tufek I, Tuna MB, Mourmouris P, et al. The incidence and sequela of lymphocele formation after robot-assisted extended pelvic lymph node

dissection. BJU Int. 2016;118:127–31. Article  PubMed  Google Scholar  * Lebeis C, Canes D, Sorcini A, Moinzadeh A. Novel technique prevents lymphoceles after transperitoneal

robotic-assisted pelvic lymph node dissection: Peritoneal flap interposition. Urology. 2015;85:1505–9. Article  PubMed  Google Scholar  * Stolzenburg JU, Wasserscheid J, Rabenalt R, Do M,

Schwalenberg T, McNeill A, et al. Reduction in incidence of lymphocele following extraperitoneal radical prostatectomy and pelvic lymph node dissection by bilateral peritoneal fenestration.

World J Urol. 2008;26:581–6. Article  PubMed  Google Scholar  * Naselli A, Andreatta R, Introini C, Fontana V, Puppo P. Predictors of Symptomatic Lymphocele After Lymph Node Excision and

Radical Prostatectomy. Urology. 2010;75:630–5. Article  PubMed  Google Scholar  * Waldert M, Remzi M, Klatte T, Klingler HC. Floseal reduces the incidence of lymphoceles after

lymphadenectomies in laparoscopic and robot-assisted extraperitoneal radical prostatectomy. J Endourol. 2011;25:969–73. Article  PubMed  Google Scholar  * Grande P, Di Pierro GB, Mordasini

L, Ferrari M, Würnschimmel C, Danuser H, et al. Prospective Randomized Trial Comparing Titanium Clips to Bipolar Coagulation in Sealing Lymphatic Vessels During Pelvic Lymph Node Dissection

at the Time of Robot-assisted Radical Prostatectomy. Eur Urol. 2017;71:155–8. Article  PubMed  Google Scholar  * Yılmaz K, Ölçücü MT, Arı Ö, Karamik K, Aktaş Y, Savaş M, et al. The Results

of Peritoneal Re-Approximation Methods on Symptomatic Lymphocele Formation in Robot-Assisted Laparoscopic Radical Prostatectomy and Extended Pelvic Lymphadenectomy. Arch Esp Urol.

2022;75:447–52. Article  PubMed  Google Scholar  * Student V, Tudos Z, Studentova Z, Cesak O, Studentova H, Repa V, et al. Effect of Peritoneal Fixation (PerFix) on Lymphocele Formation in

Robot-assisted Radical Prostatectomy with Pelvic Lymphadenectomy: Results of a Randomized Prospective Trial. Eur Urol. 2023;83:154–62. Article  PubMed  Google Scholar  * Neuberger M,

Kowalewski K, Simon V, von Hardenberg J, Siegel F, Wessels F, et al. Peritoneal Flap for Lymphocele Prophylaxis Following Robotic-assisted Radical Prostatectomy with Lymph Node Dissection:

The Randomised Controlled Phase 3 PELYCAN Trial. Eur Urol Oncol. 2023; https://doi.org/10.1016/j.euo.2023.07.009 S2588-931100152-9. * Bründl J, Lenart S, Stojanoski G, Gilfrich C,

Rosenhammer B, Stolzlechner M, et al. Peritoneal flap in robot-assisted radical prostatectomy: Results of a multicenter, randomized, single-blind study (PIANOFORTE) of the efficacy in

reducing postoperative lymphocele. Dtsch Arztebl Int 2020;117:243–50. PubMed  PubMed Central  Google Scholar  * Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al.

The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. Article  PubMed  PubMed Central  Google Scholar  * Bramer WM, Rethlefsen ML, Kleijnen J,

Franco OH. Optimal database combinations for literature searches in systematic reviews: A prospective exploratory study. Syst Rev. 2017;6:245. Article  PubMed  PubMed Central  Google Scholar

  * Amir-Behghadami M, Janati A. Population, Intervention, Comparison, Outcomes and Study (PICOS) design as a framework to formulate eligibility criteria in systematic reviews. Emerg Med J.

2020;37:387. Article  PubMed  Google Scholar  * Motterle G, Morlacco A, Zanovello N, Ahmed ME, Zattoni F, Karnes RJ, et al. Surgical Strategies for Lymphocele Prevention in Minimally

Invasive Radical Prostatectomy and Lymph Node Dissection: A Systematic Review. J Endourol. 2020;34:113–20. Article  PubMed  Google Scholar  * Dindo D, Demartines N, Clavien PA.

Classification of surgical complications: A new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13. Article  PubMed  PubMed Central 

Google Scholar  * Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

Article  PubMed  Google Scholar  * Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: A tool for assessing risk of bias in non-randomised studies of

interventions. BMJ. 2016;355:i4919. Article  PubMed  PubMed Central  Google Scholar  * Howick J, Chalmers I, Glasziou P, Greenhalgh T, Heneghan C, Liberatiet A, al. The Oxford 2011 Levels of

Evidence. https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence. Last access: August 12, 2023. * Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and

standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135. Article  PubMed  PubMed Central  Google Scholar  * Ma J, Liu W, Hunter

A, Zhang W. Performing meta-analysis with incomplete statistical information in clinical trials. BMC Med Res Methodol. 2008;8:56. Article  PubMed  PubMed Central  Google Scholar  * Higgins

JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58. Article  PubMed  Google Scholar  * Lin L, Chu H. Quantifying publication bias in meta-analysis.

Biometrics. 2018;74:785–94. Article  PubMed  Google Scholar  * Wagner J, McLaughlin T, Pinto K, Tortora J, Gangakhedkar A, Staff I. The Effect of a Peritoneal Iliac Flap on Lymphocele

Formation After Robotic Radical Prostatectomy: Results From the PLUS Trial. Urology. 2023;173:104–10. Article  PubMed  Google Scholar  * Harland N, Alfarra M, Erne E, Maas M, Amend B, Bedke

J, et al. A Peritoneal Purse-String Suture Prevents Symptomatic Lymphoceles in Retzius-Sparing Robot-Assisted Radical Prostatectomy. J Clin Med. 2023;12:791. Article  PubMed  PubMed Central

  Google Scholar  * Gloger S, Ubrig B, Boy A, Leyh-Bannurah SR, Siemer S, Arndt M, et al. Bilateral Peritoneal Flaps Reduce Incidence and Complications of Lymphoceles after Robotic Radical

Prostatectomy with Pelvic Lymph Node Dissection - Results of the Prospective Randomized Multicenter Trial ProLy. J Urol. 2022;208:333–40. Article  PubMed  PubMed Central  Google Scholar  *

Boğa MS, Sönmez MG, Karamik K, Yilmaz K, Savaş M, Ateş M. The effect of peritoneal re-approximation on lymphocele formation in transperitoneal robot-assisted radical prostatectomy and

extended pelvic lymphadenectomy. Turk J Urol. 2020;46:460–7. Article  PubMed  PubMed Central  Google Scholar  * Lee M, Lee Z, Eun DD. Utilization of a Peritoneal Interposition Flap to

Prevent Symptomatic Lymphoceles after Robotic Radical Prostatectomy and Bilateral Pelvic Lymph Node Dissection. J Endourol. 2020;34:821–7. Article  PubMed  Google Scholar  * Dal Moro F,

Zattoni F. P.L.E.A.T.—Preventing Lymphocele Ensuring Absorption Transperitoneally: A Robotic Technique. Urology. 2017;110:244–7. Article  PubMed  Google Scholar  * Pose RM, Knipper S,

Würnschimmel C, Tennstedt P, Michl U, Maurer T, et al. Significant reduction of lymphoceles after radical prostatectomy and pelvic lymph node dissection. BJU Int. 2021;128:728–33. Article 

PubMed  Google Scholar  * Kallappan S, Manickam R, Nachimuthu S, Ganesapandi T. Unusual lymphocele following radical cystectomy with orthotopic neobladder. Indian J Urol. 2019;35:168–9.

Article  PubMed  PubMed Central  Google Scholar  * Basourakos SP, Zhu A, Lewicki PJ, Ramaswamy A, Cheng E, Dudley V, et al. Clipless Robotic-assisted Radical Prostatectomy and Impact on

Outcomes. Eur Urol Focus. 2022;8:1176–85. Article  PubMed  Google Scholar  * Danuser H, Di Pierro GB, Stucki P, Mattei A. Extended pelvic lymphadenectomy and various radical prostatectomy

techniques: Is pelvic drainage necessary? BJU Int. 2013;111:963–9. Article  PubMed  Google Scholar  * Territo A, Baboudjian M, Diana P, Gallioli A, Verri P, Uleri A, et al. To drain or not

to drain in uro-oncological robotic surgery? A systematic review and meta-analysis. Minerva Urol Nephrol. 2023;75:144–53. Article  PubMed  Google Scholar  * Capitanio U, Pellucchi F, Gallina

A, Briganti A, Suardi N, Salonia A, et al. How can we predict lymphorrhoea and clinically significant lymphocoeles after radical prostatectomy and pelvic lymphadenectomy? Clinical

implications. BJU Int. 2011;107:1095–101. Article  PubMed  Google Scholar  * Seetharam Bhat KR, Onol F, Rogers T, Ganapathi HP, Moschovas M, Roof S, et al. Can we predict who will need

lymphocele drainage following robot assisted laparoscopic prostatectomy (RALP)? J Robot Surg. 2020;14:439–45. Article  CAS  PubMed  Google Scholar  * May M, Gilfrich C, Bründl J, Ubrig B,

Wagner JR, Gloger S, et al. Impact of Peritoneal Interposition Flap on Patients Undergoing Robot-assisted Radical Prostatectomy and Pelvic Lymph Node Dissection: A Systematic Review and

Meta-analysis of Randomized Controlled Trials. Eur Urol Focus. 2023. https://doi.org/10.1016/j.euf.2023.07.007 S2405-456900181-5. Download references AUTHOR INFORMATION Author notes * These

authors contributed equally: Francesco Ditonno, Celeste Manfredi, Antonio Franco. AUTHORS AND AFFILIATIONS * Department of Urology, Rush University Medical Center, Chicago, IL, USA Francesco

Ditonno, Celeste Manfredi, Antonio Franco & Riccardo Autorino * Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy Francesco

Ditonno, Alessandro Veccia & Alessandro Antonelli * Unit of Urology, Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples,

Italy Celeste Manfredi & Marco De Sio * Department of Urology, Sant’Andrea Hospital, Sapienza University, Rome, Italy Antonio Franco & Cosimo De Nunzio * Department of Surgery,

Oncology, and Gastroenterology, Urology Clinic, University of Padua, Padua, Italy Fabrizio Dal Moro Authors * Francesco Ditonno View author publications You can also search for this author

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You can also search for this author inPubMed Google Scholar * Cosimo De Nunzio View author publications You can also search for this author inPubMed Google Scholar * Marco De Sio View author

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Riccardo Autorino View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Conceptualization and supervision: RA; Study screening, paper selection,

data extraction, and risk of bias assessment: FD, AF; Data analysis and interpretation: FD, CM; Paper drafting: FD, CM, AF; Drawing: FDM; Statistical review: AV; Scientific and grammatical

review: AA, CDN, MDS. All authors approved the final version of the paper. CORRESPONDING AUTHOR Correspondence to Riccardo Autorino. ETHICS DECLARATIONS COMPETING INTERESTS The authors

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formation after robot-assisted radical prostatectomy with pelvic lymph node dissection: a systematic review and meta-analysis of randomized controlled trials. _Prostate Cancer Prostatic Dis_

27, 635–644 (2024). https://doi.org/10.1038/s41391-023-00744-5 Download citation * Received: 28 August 2023 * Revised: 11 October 2023 * Accepted: 12 October 2023 * Published: 24 October

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