Abstract
Purpose
To demonstrate the benefits of fluorescence-supported extended pelvic lymph node dissection (ePLND) compared to regular ePLND in robot-assisted radical prostatectomy.
Methods
120 patients with intermediate- or high-risk prostate cancer were prospectively randomized (1:1): in the intervention group, indocyanine green (ICG) was injected transrectally into the prostate before docking of the robot. In both groups, ePLND was performed including additional dissection of fluorescent lymph nodes (LN) in the ICG group.
Results
After drop-out of two patients, 59 patients were allocated to the control (A) and intervention group (B) with a median PSA of 8,6 ng/ml. Median console time was 159 (A) vs. 168 (B) min (p = 0.20) with a longer time for ICG-ePLND: 43 (A) vs. 55 min (B) (p = 0.001). 2609 LN were found with significantly more LN after ICG-supported ePLND with a median of 25 vs. 17 LN in A (p < 0.001). Nodal metastases were detected in 6 patients in A (25 cancerous LN) vs. 9 patients in B (62 positive LN) (p = 0.40). In seven of nine patients, ICG-ePLND identified at least one cancer-positive LN (sensitivity 78%), 27 of 62 cancerous LN were fluorescent. Symptomatic lymphocele occurred in one patient in a and in three patients in b (p = 0.62). After a median follow-up of 22.9 months, PSA levels were similar.
Conclusions
While ICG-ePLND seems to be beneficial for a better understanding of the lymphatic drainage and a more meticulous diagnostic approach, the sensitivity is not sufficient to recommend stand-alone ICG lymph node dissection.
Similar content being viewed by others
References
Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics, 2014. CA Cancer J Clin 64(1):9–29. https://doi.org/10.3322/caac.21208
D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A (1998) Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280(11):969–974
Engel J, Bastian PJ, Baur H, Beer V, Chaussy C, Gschwend JE, Oberneder R, Rothenberger KH, Stief CG, Holzel D (2010) Survival benefit of radical prostatectomy in lymph node-positive patients with prostate cancer. Eur Urol 57(5):754–761. https://doi.org/10.1016/j.eururo.2009.12.034
Heidenreich A, Pfister D, Porres D (2015) Cytoreductive radical prostatectomy in patients with prostate cancer and low volume skeletal metastases: results of a feasibility and case-control study. J Urol 193(3):832–838. https://doi.org/10.1016/j.juro.2014.09.089
Briganti A, Chun FK, Salonia A, Zanni G, Scattoni V, Valiquette L, Rigatti P, Montorsi F, Karakiewicz PI (2006) Validation of a nomogram predicting the probability of lymph node invasion among patients undergoing radical prostatectomy and an extended pelvic lymphadenectomy. Eur Urol 49(6):1019–1026. https://doi.org/10.1016/j.eururo.2006.01.043 Discussion 1026–1017
Briganti A, Larcher A, Abdollah F, Capitanio U, Gallina A, Suardi N, Bianchi M, Sun M, Freschi M, Salonia A, Karakiewicz PI, Rigatti P, Montorsi F (2012) Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol 61(3):480–487. https://doi.org/10.1016/j.eururo.2011.10.044
Shariat SF, Karakiewicz PI, Suardi N, Kattan MW (2008) Comparison of nomograms with other methods for predicting outcomes in prostate cancer: a critical analysis of the literature. Clin Cancer Res 14(14):4400–4407. https://doi.org/10.1158/1078-0432.CCR-07-4713
Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, Wester HJ, Heck M, Kubler H, Beer AJ, Schwaiger M, Eiber M (2016) Diagnostic efficacy of (68)gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol 195(5):1436–1443. https://doi.org/10.1016/j.juro.2015.12.025
Mattei A, Fuechsel FG, Bhatta Dhar N, Warncke SH, Thalmann GN, Krause T, Studer UE (2008) The template of the primary lymphatic landing sites of the prostate should be revisited: results of a multimodality mapping study. Eur Urol 53(1):118–125. https://doi.org/10.1016/j.eururo.2007.07.035
Harbin AC, Eun DD (2015) The role of extended pelvic lymphadenectomy with radical prostatectomy for high-risk prostate cancer. Urol Oncol 33(5):208–216. https://doi.org/10.1016/j.urolonc.2014.11.011
Cabanas RM (1977) An approach for the treatment of penile carcinoma. Cancer 39(2):456–466
Wawroschek F, Vogt H, Weckermann D, Wagner T, Harzmann R (1999) The sentinel lymph node concept in prostate cancer—first results of gamma probe-guided sentinel lymph node identification. Eur Urol 36(6):595–600. https://doi.org/10.1159/000020054
Jeschke S, Beri A, Grull M, Ziegerhofer J, Prammer P, Leeb K, Sega W, Janetschek G (2008) Laparoscopic radioisotope-guided sentinel lymph node dissection in staging of prostate cancer. Eur Urol 53(1):126–132. https://doi.org/10.1016/j.eururo.2007.03.064
van der Poel HG, Buckle T, Brouwer OR, Valdes Olmos RA, van Leeuwen FW (2011) Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer. Eur Urol 60(4):826–833. https://doi.org/10.1016/j.eururo.2011.03.024
Manny TB, Patel M, Hemal AK (2014) Fluorescence-enhanced robotic radical prostatectomy using real-time lymphangiography and tissue marking with percutaneous injection of unconjugated indocyanine green: the initial clinical experience in 50 patients. Eur Urol 65(6):1162–1168. https://doi.org/10.1016/j.eururo.2013.11.017
Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213
Wit EMK, Acar C, Grivas N, Yuan C, Horenblas S, Liedberg F, Valdes Olmos RA, van Leeuwen FWB, van den Berg NS, Winter A, Wawroschek F, Hruby S, Janetschek G, Vidal-Sicart S, MacLennan S, Lam TB, van der Poel HG (2017) Sentinel node procedure in prostate cancer: a systematic review to assess diagnostic accuracy. Eur Urol 71(4):596–605. https://doi.org/10.1016/j.eururo.2016.09.007
Hruby S, Englberger C, Lusuardi L, Schatz T, Kunit T, Abdel-Aal AM, Hager M, Janetschek G (2015) Fluorescence guided targeted pelvic lymph node dissection for intermediate and high risk prostate cancer. J Urol 194(2):357–363. https://doi.org/10.1016/j.juro.2015.03.127
Nguyen DP, Huber PM, Metzger TA, Genitsch V, Schudel HH, Thalmann GN (2016) A specific mapping study using fluorescence sentinel lymph node detection in patients with intermediate- and high-risk prostate cancer undergoing extended pelvic lymph node dissection. Eur Urol 70(5):734–737. https://doi.org/10.1016/j.eururo.2016.01.034
KleinJan GH, van den Berg NS, Brouwer OR, de Jong J, Acar C, Wit EM, Vegt E, van der Noort V, Valdes Olmos RA, van Leeuwen FW, van der Poel HG (2014) Optimisation of fluorescence guidance during robot-assisted laparoscopic sentinel node biopsy for prostate cancer. Eur Urol 66(6):991–998. https://doi.org/10.1016/j.eururo.2014.07.014
KleinJan GH, van den Berg NS, de Jong J, Wit EM, Thygessen H, Vegt E, van der Poel HG, van Leeuwen FW (2016) Multimodal hybrid imaging agents for sentinel node mapping as a means to (re)connect nuclear medicine to advances made in robot-assisted surgery. Eur J Nucl Med Mol Imaging 43(7):1278–1287. https://doi.org/10.1007/s00259-015-3292-2
Ramirez-Backhaus M, Mira Moreno A, Gomez Ferrer A, Calatrava Fons A, Casanova J, Solsona Narbon E, Ortiz Rodriguez IM, Rubio Briones J (2016) Indocyanine green guided pelvic lymph node dissection: an efficient technique to classify the lymph node status of patients with prostate cancer who underwent radical prostatectomy. J Urol 196(5):1429–1435. https://doi.org/10.1016/j.juro.2016.05.087
Yuen K, Miura T, Sakai I, Kiyosue A, Yamashita M (2015) Intraoperative fluorescence imaging for detection of sentinel lymph nodes and lymphatic vessels during open prostatectomy using indocyanine green. J Urol 194(2):371–377. https://doi.org/10.1016/j.juro.2015.01.008
Weckermann D, Dorn R, Holl G, Wagner T, Harzmann R (2007) Limitations of radioguided surgery in high-risk prostate cancer. Eur Urol 51(6):1549–1556. https://doi.org/10.1016/j.eururo.2006.08.049 Discussion 1556–1548
Joniau S, Van den Bergh L, Lerut E, Deroose CM, Haustermans K, Oyen R, Budiharto T, Ameye F, Bogaerts K, Van Poppel H (2013) Mapping of pelvic lymph node metastases in prostate cancer. Eur Urol 63(3):450–458. https://doi.org/10.1016/j.eururo.2012.06.057
Abdollah F, Gandaglia G, Suardi N, Capitanio U, Salonia A, Nini A, Moschini M, Sun M, Karakiewicz PI, Shariat SF, Montorsi F, Briganti A (2015) More extensive pelvic lymph node dissection improves survival in patients with node-positive prostate cancer. Eur Urol 67(2):212–219. https://doi.org/10.1016/j.eururo.2014.05.011
Schiavina R, Bianchi L, Borghesi M, Briganti A, Brunocilla E, Carini M, Terrone C, Mottrie A, Dente D, Gacci M, Gontero P, Gurioli A, Imbimbo C, La Manna G, Marchioro G, Milanese G, Mirone V, Montorsi F, Morgia G, Munegato S, Novara G, Panarello D, Porreca A, Russo GI, Serni S, Simonato A, Urzi D, Verze P, Volpe A, Martorana G (2016) Predicting survival in node-positive prostate cancer after open, laparoscopic or robotic radical prostatectomy: a competing risk analysis of a multi-institutional database. Int J Urol 23(12):1000–1008. https://doi.org/10.1111/iju.13203
Grivas N, Wit E, Kuusk T, KleinJan G, Donswijk M, van Leeuwen F, van der Poel H (2017) The impact of adding sentinel node biopsy to extended pelvic lymph node dissection on the biochemical recurrence of prostate cancer patients treated with robot-assisted radical prostatectomy. J Nucl Med. https://doi.org/10.2967/jnumed.117.195644
Author information
Authors and Affiliations
Contributions
NH Protocol/project development, data collection and management, data analysis, manuscript writing; MG Protocol/project development, data collection and management; CW Data collection and management, manuscript editing; MA Data collection and management; BF Data collection and management; KU Data collection and management, manuscript editing; BH Manuscript editing; JHW Protocol/project development, data collection and management, manuscript editing
Corresponding author
Ethics declarations
Compliance with ethical standards
All procedures in this study involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.Informed consent was obtained from all individual participants included in the study.
Conflicts of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Harke, N.N., Godes, M., Wagner, C. et al. Fluorescence-supported lymphography and extended pelvic lymph node dissection in robot-assisted radical prostatectomy: a prospective, randomized trial. World J Urol 36, 1817–1823 (2018). https://doi.org/10.1007/s00345-018-2330-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00345-018-2330-7