Prognostic significance of lymphovascular invasion in radical prostatectomy specimens

Study Type – Prognosis (systematic review) Level of Evidence 1a What's known on the subject? and What does the study add? Prognostic factors such as serum PSA, tumor T stage, and Gleason grading are commonly used to predict disease progression and mortality in prostate cancer and to guide treatment decision-making. These markers are combined to define risk strata that are commonly accepted in practice. Despite the assignment of patients to a specific risk stratum (e.g. intermediate-risk disease), however, within-stratum survival duration varies considerably, suggesting that many other factors, including lymphovascular invasion (LVI) may influence prognosis. LVI is currently a recognized prognostic factor in the management of some cancers (e.g. in early-stage breast cancer) and prostate cancer is known to spread via lymphatic channels. Furthermore, the reporting of microscopic lymphovascular invasion is now considered part of the standard pathologic report of prostatectomy specimens. Nevertheless, scientific studies in this area have produced conflicting conclusions regarding the utility of LVI as a prognostic indicator in prostate cancer. This paper provides a comprehensive review and synthesis of the recent literature. Although a number of studies examining the role of LVI as an independent prognostic factor for biochemical recurrence in prostate cancer have been reported, the characteristics, quality and results of these studies vary considerably. The value of using LVI as a prognostic factor in prostate cancer remains unclear. This study provides a systematically-performed synthesis of the results of recent research including lymphovascular invasion (LVI) in the multivariate analyses of potential prostate cancer prognostic factors. Not only do we report on the results of these studies, we assess the heterogeneity of the study populations, disease characteristics, and quality of the studies. Ultimately, we determined that meta-analysis of the existing data is not possible, and thus, there is no ‘best estimate’ of the strength of association between LVI status and disease recurrence after prostatectomy. Most studies, but not all, reveal a weak or statistically insignificant association between LVI status and recurrence. We therefore conclude with a recommendation to clinicians that they should not overweight the importance of LVI status on clinical prognostication. The use of LVI status as a strong predictor of clinical outcomes is not recommended. OBJECTIVES •  To synthesize the results of studies including lymphovascular invasion (LVI) in the multivariate analyses of potential prostate cancer prognostic factors. •  To determine the role of LVI as an independent prognostic factor for biochemical recurrence in prostate cancer. PATIENTS AND METHODS •  We performed a comprehensive systematic literature review of studies examining the association between LVI in prostatectomy specimens and prostate cancer recurrence. •  Ovid MEDLINE, Embase, Web of Knowledge, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects (DARE) and Google Scholar were searched from January 2000 to February 2009. •  The primary outcome of interest was biochemical recurrence measured by serum prostate specific antigen (PSA). RESULTS •  One thousand two hundred and forty-eight papers met our search criteria. Of these, 19 articles meeting our selection criteria reported results of a multivariate analysis to evaluate LVI as an independent prognostic factor of biochemical recurrence. •  Eleven (58%) of these studies concluded that LVI was an independent prognostic factor. •  Significant heterogeneity in the study population, disease characteristics and quality of the studies prevented meta-analysis of the results. •  In the nine studies in which the magnitude of independent association of LVI with recurrence was reported, it ranged from an odds ratio or relative risk of 1.37 to 4.39. CONCLUSIONS •  The existing literature is conflicting and of insufficient homogeneity to definitively establish LVI as an important independent prognostic factor of biochemical recurrence in prostate cancer prostatectomy specimens. •  Additional adequately powered studies are required to determine the clinical value of reports of LVI involvement. •  In the meantime, the use of LVI status as an independent prognostic factor for clinical prognostication and medical decision making is not recommended.