The Benefits and Harms of Different Extents of Lymph Node Dissection During Radical Prostatectomy for Prostate Cancer: A Systematic Review

Abstract

Context

There is controversy regarding the therapeutic role of pelvic lymph node dissection (PLND) in patients undergoing radical prostatectomy for prostate cancer (PCa).

Objective

To systematically review the relevant literature assessing the relative benefits and harms of PLND for oncological and non-oncological outcomes in patients undergoing radical prostatectomy for PCa.

Evidence acquisition

MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched up to December 2015. Comparative studies evaluating no PLND, limited, standard, and (super)-extended PLND that reported oncological and non-oncological outcomes were included. Risk-of-bias and confounding assessments were performed. A narrative synthesis was undertaken.

Evidence synthesis

Overall, 66 studies recruiting a total of 275,269 patients were included (44 full-text articles and 22 conference abstracts). Oncological outcomes were addressed by 29 studies, one of which was a randomized clinical trial (RCT). Non-oncological outcomes were addressed by 43 studies, three of which were RCTs. There were high risks of bias and confounding in most studies. Conflicting results emerged when comparing biochemical and clinical recurrence, while no significant differences were observed among groups for survival. Conversely, the majority of studies showed that the more extensive the PLND, the greater the adverse outcomes in terms of operating time, blood loss, length of stay, and postoperative complications. No significant differences were observed in terms of urinary continence and erectile function recovery.

Conclusions

Although representing the most accurate staging procedure, PLND and its extension are associated with worse intraoperative and perioperative outcomes, whereas a direct therapeutic effect is still not evident from the current literature. The current poor quality of evidence indicates the need for robust and adequately powered clinical trials.

Patient summary

Based on a comprehensive review of the literature, this article summarizes the benefits and harms of removing lymph nodes during surgery to remove the prostate because of PCa. Although the quality of the data from the studies was poor, the review suggests that lymph node removal may not have any direct benefit on cancer outcomes and may instead result in more complications. Nevertheless, the procedure remains justified because it enables accurate assessment of cancer spread.

Introduction

The current European Association of Urology (EAU) prostate cancer (PCa) guidelines recommend performing extended pelvic lymph node dissection (PLND) in high-risk and intermediate-risk patients when the estimated risk for positive lymph nodes exceeds 5% [1]. However, the therapeutic role of PLND during radical prostatectomy for the management of PCa remains controversial. There are reports suggesting that PLND results in improved pathological staging, and that extending the PLND template may increase its staging accuracy. Nevertheless, the oncological benefit of the procedure is still unclear [2].

Historically, the decision to perform PLND, and on how extensive it ought to be, has been left to the clinical judgment of the surgeon. The lack of clarity regarding the oncological benefit of performing PLND, and the lack of standardized definitions and terminologies regarding the PLND template, have led to a wide variety of “experience-based approaches” [3], [4] which render any comparisons between them difficult and fraught with uncertainties. It is also unclear whether the PLND outcomes vary between different patient subgroups (ie, low- vs intermediate- vs high-risk localized disease). Furthermore, PLND may be associated with an increased risk of adverse events, morbidity, length of stay, and healthcare costs. However, the assertion that more extensive PLND leads to higher complication rates has not always been confirmed [5], [6], [7].

The objective of this systematic review was to evaluate the benefits and harms of PLND, incorporating the comparison between PLND of differing extent (ie, no PLND, limited PLND, standard PLND, extended PLND, and super-extended PLND) during radical prostatectomy for PCa, and to identify which patients benefit most from PLND.