Genomic Classifiers and Prognosis of Localized Prostate Cancer: A Systematic Review

Abstract Background Refinement of the risk classification for localized prostate cancer is warranted to aid in clinical decision making. A systematic analysis was undertaken to evaluate the prognostic ability of three genomic classifiers, Decipher, GPS, and Prolaris, for biochemical recurrence, development of metastases and prostate cancer specific mortality in patients with localized prostate cancer. Methods Data Sources: MEDLINE, Embase, and Web of Science were queried for reports published January 2010 to April 2022. Study Selection: Prospective or retrospective studies reporting prognosis for patients with localized prostate cancer. Data Extraction: Relevant data were extracted into a customized database by 1 researcher with a second over reading. Risk of bias was assessed using a validated tool for prognostic studies, Quality in Prognosis Studies (QUIPS). Disagreements were resolved by consensus or by input from a third reviewer. We assessed certainty of evidence by GRADE incorporating adaptation for prognostic studies. Results Data Synthesis: A total of 39 studies (37 retrospective) involving over 10 000 patients were identified. Twenty-two assessed Decipher, 5 GPS, and 14 Prolaris. Thirty-four studies included patients who underwent prostatectomy. Based on very low to low certainty of evidence, each of three genomic classifiers modestly improved upon the prognostic ability for biochemical recurrence, development of metastases, and prostate cancer specific mortality compared to standard clinical risk classification schemes Limitations: Downgrading of confidence in the evidence stemmed largely from bias due to the retrospective nature of the studies, heterogeneity in treatment received, and era in which patients were treated (i.e., prior to 2000s). Conclusions: Genomic classifiers provide a small but consistent improvement upon the prognostic ability of clinical classification schemes which may be helpful when treatment decisions are uncertain. However, definitive evidence from current management-era data is needed.