Lisa Moris1, Giorgio Gandaglia2, Antoni Vilaseca3, Thomas Van den Broeck4, Erik Briers5, Maria De Santis6, Silke Gillessen7, Nikos Grivas8, Shane O'Hanlon9, Ann Henry10, Thomas B Lam11, Michael Lardas12, Malcolm Mason13, Daniela Oprea-Lager14, Guillaume Ploussard15, Olivier Rouviere16, Ivo G Schoots17, Henk van der Poel18, Thomas Wiegel19, Peter-Paul Willemse20, Cathy Y Yuan21, Jeremy P Grummet22, Derya Tilki23, Roderick C N van den Bergh24, Philip Cornford25, Nicolas Mottet26. 1. Department of Urology, University Hospitals Leuven, Leuven, Belgium. Electronic address: lisa.moris1506@gmail.com. 2. Unit of Urology, Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy. 3. Uro-Oncology Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain. 4. Department of Urology, University Hospitals Leuven, Leuven, Belgium. 5. Patient Advocate, Hasselt, Belgium. 6. Department of Urology, Charité University Hospital Berlin, Berlin, Germany; Department of Urology, Medical University of Vienna, Vienna, Austria. 7. Oncology Institute of Southern Switzerland, Bellinzona, Switzerland; Università della Svizzera Italiana, Lugano, Switzerland. 8. Department of Urology, Hatzikosta General Hospital, Ioannina, Greece. 9. Medicine for Older People, Saint Vincent's University Hospital, Dublin, Ireland. 10. Leeds Cancer Centre, St. James's University Hospital and University of Leeds, Leeds, UK. 11. Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK. 12. Department of Urology, Metropolitan General Hospital, Athens, Greece. 13. Division of Cancer & Genetics, School of Medicine Cardiff University, UK. 14. Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, VU University, Amsterdam, The Netherlands. 15. La Croix du Sud Hospital, Quint Fonsegrives, France. 16. Department of Urinary and Vascular Imaging, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France. 17. Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 18. Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands. 19. Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany. 20. Department of Oncological Urology, Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands. 21. Department of Medicine, Health Science Centre, McMaster University, Hamilton, ON, Canada. 22. Department of Surgery, Central Clinical School, Monash University, Melbourne, Australia. 23. Martini-Klinik Prostate Cancer Center and Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. 24. Department of Urology, Antonius Hospital, Utrecht, The Netherlands. 25. Department of Urology, Liverpool University Hospitals NHS Trust, Liverpool, UK. 26. Department of Urology, University Hospital, St. Etienne, France.
Abstract
CONTEXT: Surgical techniques aimed at preserving the neurovascular bundles during radical prostatectomy (RP) have been proposed to improve functional outcomes. However, it remains unclear if nerve-sparing (NS) surgery adversely affects oncological metrics. OBJECTIVE: To explore the oncological safety of NS versus non-NS (NNS) surgery and to identify factors affecting the oncological outcomes of NS surgery. EVIDENCE ACQUISITION: Relevant databases were searched for English language articles published between January 1, 1990 and May 8, 2020. Comparative studies for patients with nonmetastatic prostate cancer (PCa) treated with primary RP were included. NS and NNS techniques were compared. The main outcomes were side-specific positive surgical margins (ssPSM) and biochemical recurrence (BCR). Risk of bias (RoB) and confounding assessments were performed. EVIDENCE SYNTHESIS: Out of 1573 articles identified, 18 studies recruiting a total of 21 654 patients were included. The overall RoB and confounding were high across all domains. The most common selection criteria for NS RP identified were characteristic of low-risk disease, including low core-biopsy involvement. Seven studies evaluated the link with ssPSM and showed an increase in ssPSM after adjustment for side-specific confounders, with the relative risk for NS RP ranging from 1.50 to 1.53. Thirteen papers assessing BCR showed no difference in outcomes with at least 12 mo of follow-up. Lack of data prevented any subgroup analysis for potentially important variables. The definitions of NS were heterogeneous and poorly described in most studies. CONCLUSIONS: Current data revealed an association between NS surgery and an increase in the risk of ssPSM. This did not translate into a negative impact on BCR, although follow-up was short and many men harbored low-risk PCa. There are significant knowledge gaps in terms of how various patient, disease, and surgical factors affect outcomes. Adequately powered and well-designed prospective trials and cohort studies accounting for these issues with long-term follow-up are recommended. PATIENT SUMMARY: Neurovascular bundles (NVBs) are structures containing nerves and blood vessels. The NVBs close to the prostate are responsible for erections. We reviewed the literature to determine if a technique to preserve the NVBs during removal of the prostate causes worse cancer outcomes. We found that NVB preservation was poorly defined but, if applied, was associated with a higher risk of cancer at the margins of the tissue removed, even in patients with low-risk prostate cancer. The long-term importance of this finding for patients is unclear. More data are needed to provide recommendations.
CONTEXT: Surgical techniques aimed at preserving the neurovascular bundles during radical prostatectomy (RP) have been proposed to improve functional outcomes. However, it remains unclear if nerve-sparing (NS) surgery adversely affects oncological metrics. OBJECTIVE: To explore the oncological safety of NS versus non-NS (NNS) surgery and to identify factors affecting the oncological outcomes of NS surgery. EVIDENCE ACQUISITION: Relevant databases were searched for English language articles published between January 1, 1990 and May 8, 2020. Comparative studies for patients with nonmetastatic prostate cancer (PCa) treated with primary RP were included. NS and NNS techniques were compared. The main outcomes were side-specific positive surgical margins (ssPSM) and biochemical recurrence (BCR). Risk of bias (RoB) and confounding assessments were performed. EVIDENCE SYNTHESIS: Out of 1573 articles identified, 18 studies recruiting a total of 21 654 patients were included. The overall RoB and confounding were high across all domains. The most common selection criteria for NS RP identified were characteristic of low-risk disease, including low core-biopsy involvement. Seven studies evaluated the link with ssPSM and showed an increase in ssPSM after adjustment for side-specific confounders, with the relative risk for NS RP ranging from 1.50 to 1.53. Thirteen papers assessing BCR showed no difference in outcomes with at least 12 mo of follow-up. Lack of data prevented any subgroup analysis for potentially important variables. The definitions of NS were heterogeneous and poorly described in most studies. CONCLUSIONS: Current data revealed an association between NS surgery and an increase in the risk of ssPSM. This did not translate into a negative impact on BCR, although follow-up was short and many men harbored low-risk PCa. There are significant knowledge gaps in terms of how various patient, disease, and surgical factors affect outcomes. Adequately powered and well-designed prospective trials and cohort studies accounting for these issues with long-term follow-up are recommended. PATIENT SUMMARY: Neurovascular bundles (NVBs) are structures containing nerves and blood vessels. The NVBs close to the prostate are responsible for erections. We reviewed the literature to determine if a technique to preserve the NVBs during removal of the prostate causes worse cancer outcomes. We found that NVB preservation was poorly defined but, if applied, was associated with a higher risk of cancer at the margins of the tissue removed, even in patients with low-risk prostate cancer. The long-term importance of this finding for patients is unclear. More data are needed to provide recommendations.