Skip to main content

Is the Recommendation of a Pelvic Lymphadenectomy in Conjunction with Radical Prostatectomy in Prostate Cancer Patients Justified? Report from a Multidisciplinary Expert Panel Meeting

Abstract

Introduction

Pelvic lymphadenectomy (pLA) in prostate cancer (PCa) is one of the most common uro-oncologic surgical procedures. An increased complication rate is accompanied by unproven oncologic benefit. Extent of pLA and mechanisms of metastasis are discussed controversially. We aimed to explore evidence and knowledge gaps in pLA and mechanisms of metastasis in PCa and to develop further steps to clarify oncologic benefits through an expert panel.

Methods

A multidisciplinary expert meeting was initiated, compiling available facts on pLA and mechanisms of metastasis in PCa. Questions and hypotheses were formulated. The resulting protocol was modeled on priority and consistency in four anonymized voting rounds using the Delphi method (March 2018–June 2018).

Results

The oncologic benefit of pLA in PCa is still unclear. Results of randomized trials (RCTs) are pending. Extent and techniques of pLA are differently applied and inconsistently recommended by the guidelines as well as the indication for pLA. Different growth rates for the primaries and metastases and different survival curves for lymph node and organ metastasis at diagnosis argue against metastasis originating from positive nodes. However, results from clinical and basic research support this opportunity in PCa.

Conclusions

The RCTs required to clarify the estimated low oncologic benefit of pLA prove to be difficult because of the great effort (e.g., high case number). Establishing a network of treatment centers for implementation of high-quality cohort studies could be an alternative approach. Future studies with larger panels and international participants based on the presented feasibility should be launched to set this process in motion. Until valid data are available, benefits and harms of pLA should be weighted under consideration of low-invasive techniques (e.g., sentinel pLA).

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. Fossati N, Willems PPM, Van den Broeck TH, et al. The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: a systematic review. Eur Urol. 2017;72:84–109.

    Article  Google Scholar 

  2. Clarke NW, Re Fossati N, Willemse PPM, Van den Broeck T, et al. The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: a systematic review. Eur Urol. 2016. https://doi.org/10.1016/j.eururo.2017.05.020(Epub ahead of print).

    Article  PubMed  Google Scholar 

  3. Briganti A, Suardi N, Gallina A, Abdollah F, Montorsi F. Pelvic lymph node dissection in prostate cancer: the mystery is taking shape. Eur Urol. 2013;63:459–61.

    Article  Google Scholar 

  4. Rees T, Raison N, Sheikh MI, et al. Is extended pelvic lymph node dissection for prostate cancer the only recommended option? A systematic over-view of the literature. Turk J Urol. 2016;42:240–6.

    Article  Google Scholar 

  5. Mottet N, van den Bergh RCN, Briers E et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. http://www.uroweb.org/guideline/penile-cancer/. Accessed 2019 Mar 30.

  6. Harter P, Sehouli J, Lorusso D, et al. LION: lymphadenectomy in ovarian neoplasms—a prospective randomized AGO study group led gynecologic cancer intergroup trial. J Clin Oncol. 2017;35(suppl):5500.

    Article  Google Scholar 

  7. Diamond IR, Grant RC, Feldman BM, et al. Defining consensus: a systematic review recommends methodologic criteria for reporting of Delphi studies. J Clin Epidemiol. 2014;67:401–9.

    Article  Google Scholar 

  8. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms, Langversion 5.0, 2018, AWMF Registernummer: 043/022OL, http://www.leitlinienprogramm-onkologie.de/leitlinien/prostatakarzinom/(abgerufen. 22 May 2018).

  9. Cabanas RM. An approach for the treatment of penile carcinoma. Cancer. 1977;39:456–66.

    CAS  Article  Google Scholar 

  10. Morton DL, Thompson JF, Cochran AJ, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370:599–609.

    CAS  Article  Google Scholar 

  11. Wawroschek F, Vogt H, Weckermann D, Wagner T, Harzmann R. The sentinel lymph node concept in prostate cancer - first results of gamma probe-guided sentinel lymph node identification Eur Urol. 1999;36:595–600.

    CAS  PubMed  Google Scholar 

  12. Wit EMK, Acar C, Grivas N, et al. Sentinel node procedure in prostate cancer: a systematic review to assess diagnostic accuracy. Eur Urol. 2017;71:596–605.

    Article  Google Scholar 

  13. Winter A, Kneib T, Wasylow C, et al. Updated nomogram incorporating percentage of positive cores to predict probability of lymph node invasion in prostate cancer patients undergoing sentinel lymph node dissection. J Cancer. 2017;8:2692–8.

    Article  Google Scholar 

  14. Mattei A, Fuechsel FG, Bhatta Dhar N, et al. The template of the primary lymphatic landing sites of the prostate should be revisited: results of a multimodality mapping study. Eur Urol. 2008;53:118–25.

    Article  Google Scholar 

  15. Briganti A, Chun FK, Salonia A, 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  Google Scholar 

  16. Winter A, Vogt C, Weckermann D, Wawroschek F. Complications of pelvic lymphadenectomy in clinically localised prostate cancer: different techniques in comparison and dependency on the number of removed lymph nodes. Aktuelle Urol. 2011;42:179–83.

    CAS  Article  Google Scholar 

  17. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging Biological Principles of Metastasis. Cell. 2017;168:670–91.

    CAS  Article  Google Scholar 

  18. Halsted WSI. The results of operations for the cure of cancer of the breast performed at the johns hopkins hospital from June, 1889 to January, 1894. Ann Surg. 1894;20:497–555.

    CAS  Article  Google Scholar 

  19. Klein CA, Hölzel D. Systemic cancer progression and tumor dormancy: mathematical models meet single cell genomics. Cell Cycle. 2006;5:1788–98.

    CAS  Article  Google Scholar 

  20. Engel J, Emeny RT, Hölzel D. Positive lymph nodes do not metastasize. Cancer Metastasis Rev. 2012;31:235–46.

    Article  Google Scholar 

  21. Tjan-Heijnen V, Viale G. The lymph node and the metastasis. N Engl J Med. 2018;378:2045–6.

    Article  Google Scholar 

  22. Sleeman JP, Nazarenko I, Thiele W. Do all roads lead to Rome? Routes to metastasis development. Int J Cancer. 2011;128:2511–26.

    CAS  Article  Google Scholar 

  23. Gundem G, Van Loo P, Kremeyer B, et al. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520:353–7.

    CAS  Article  Google Scholar 

  24. Hong WS, Shpak M, Townsend JP. Inferring the origin of metastases from cancer phylogenies. Cancer Res. 2015;75:4021–5.

    CAS  Article  Google Scholar 

  25. Seiler R, Studer UE, Tschan K, Bader P, Burkhard FC. Removal of limited nodal disease in patients undergoing radical prostatectomy: long-term results confirm a chance for cure. J Urol. 2014;191:1280–5.

    Article  Google Scholar 

  26. Joslyn SA, Konety BR. Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer. Urology. 2006;68:121–5.

    Article  Google Scholar 

  27. Abdollah F, Gandaglia G, Suardi N, et al. More extensive pelvic lymph node dissection improves survival in patients with node-positive prostate cancer. Eur Urol. 2015;67:212–9.

    Article  Google Scholar 

  28. Schiavina R, Manferrari F, Garofalo M, et al. The extent of pelvic lymph node dissection correlates with the biochemical recurrence rate in patients with intermediate- and high-risk prostate cancer. BJU Int. 2011;108:1262–8.

    CAS  Article  Google Scholar 

  29. Winter A, Henke RP. Wawroschek F Targeted salvage lymphadenectomy in patients treated with radical prostatectomy with biochemical recurrence: complete biochemical response without adjuvant therapy in patients with low volume lymph node recurrence over a long-term follow-up. BMC Urol. 2015;21(15):10. https://doi.org/10.1186/s12894-015-0004-y.

    CAS  Article  Google Scholar 

  30. Feinstein AR, Sosin DM, Wells CK. The Will Rogers phenomenon. Stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med. 1985;312:1604–8.

    CAS  Article  Google Scholar 

  31. Faries MB, Thompson JF, Cochran AJ, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;376:2211–22.

    Article  Google Scholar 

  32. Williams SD, Stablein DM, Einhorn LH, et al. Immediate adjuvant chemotherapy versus observation with treatment at relapse in pathological stage II testicular cancer. N Engl J Med. 1987;317:1433–8.

    CAS  Article  Google Scholar 

  33. Ross HM, Kryvenko ON, Cowan JE, Simko JP, Wheeler TM, Epstein JI. Do adenocarcinomas of the prostate with Gleason score (GS) ≤ 6 have the potential to metastasize to lymph nodes? Am J Surg Pathol. 2012;36:1346–52.

    Article  Google Scholar 

  34. Lestingi JFP, Guglielmetti G, Pontes J Jr, et al. Extended versus limited pelvic lymphadenectomy during radical prostatectomy for intermediate- and high-risk prostate cancer: early outcomes from a randomized controlled phase III study. J Clin Oncol. 2017;35(15 Suppl):5018.

    Article  Google Scholar 

  35. Ahlgren GM, Flodgren P, Tammela TLJ, et al. Docetaxel Versus Surveillance after radical prostatectomy for high-risk prostate cancer: results from the prospective randomised, open-label phase 3 Scandinavian Prostate Cancer Group 12 Trial. Eur Urol. 2018;73:870–6.

    CAS  Article  Google Scholar 

  36. Wit EMK, Acar C, Grivas N, et al. Sentinel node procedure in prostate cancer: a systematic review to assess diagnostic accuracy. Eur Urol. 2016;71:596–605.

    Article  Google Scholar 

  37. Wedge DC, Gundem G, Mitchell T, et al. Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets. Nat Genet. 2018;50:682–92.

    CAS  Article  Google Scholar 

  38. Hershman DL, Wright JD. Comparative effectiveness research in oncology methodology: observational data. J Clin Oncol. 2012;30:4215–22.

    Article  Google Scholar 

  39. McCulloch P, Feinberg J, Philippou Y, et al. Progress in clinical research in surgery and IDEAL. Lancet. 2018;392:88–94.

    Article  Google Scholar 

  40. McCulloch P, Altman DG, Campbell WB, et al. No surgical innovation without evaluation: the IDEAL recommendations. Lancet. 2009;374:1105–12.

    Article  Google Scholar 

  41. van der Poel HG, Wit EM, Acar C, et al. Sentinel node biopsy for prostate cancer: report from a consensus panel meeting. BJU Int. 2017;120:204–11.

    Article  Google Scholar 

Download references

Acknowledgements

Funding

No funding or sponsorship was received for this study or publication of this article. The Rapid Service Fee was funded by the authors.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Additional Assistance

We thank Prof. Dieter Hölzel [Munich Cancer Registry (MCR) of the Munich Cancer Centre (MCC), Institute for Medical Information Processing, Biometry and Epidemiology (IBE), Klinikum der Universität München (KUM), Ludwig Maximilian University (LMU), Munich, Germany] for participating in the expert panel, his continuous suggestions and the critical review of the manuscript.

Disclosures

C Roloff and R Harzmann are retired from their former institutions. A Winter, R Harzmann, JJ Wendler, C Roloff and S Weikert have nothing to disclose. L Weissbach is a member of the "Expert Panel Urology" of the AOK (Allgemeine Ortskrankenkasse), one of the German statutory health insurances.

Compliance with Ethics Guidelines

The protocol followed in this study was in accordance with ethical standards of the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. Ethical approval/informed consent was unnecessary because this study based on analysis of the results of previous studies.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alexander Winter.

Additional information

Enhanced Digital Features

To view enhanced digital features for this article go to https://doi.org/10.6084/m9.figshare.10003205.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Winter, A., Harzmann, R., Wendler, J.J. et al. Is the Recommendation of a Pelvic Lymphadenectomy in Conjunction with Radical Prostatectomy in Prostate Cancer Patients Justified? Report from a Multidisciplinary Expert Panel Meeting. Adv Ther 37, 213–224 (2020). https://doi.org/10.1007/s12325-019-01133-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-019-01133-y

Keywords

  • Delphi method
  • Lymph node dissection
  • Metastasis
  • Oncologic outcome
  • Prostate cancer