Transcript analysis of commercial prostate cancer risk stratification panels in hard‐to‐predict grade group 2–4 prostate cancers

Abstract

Background Improved prognostication is needed to minimize overtreatment in grade group (GG) 2–4 prostate cancer. Our aim was to determine, at messenger RNA (mRNA) level, the performance of the genes in the commercial panels Decipher, Oncotype DX, Prolaris, and mutational panel MSK‐IMPACT to predict metastasis‐free and prostate cancer‐specific death (PCSD) in patients with GG 2–4 prostate cancer at radical prostatectomy. Methods The retrospective cohort consisted of GG 2–4 patients treated with radical prostatectomy (median follow‐up 10.4 years). Seventy‐six cases with postoperative metastasis or PCSD and 84 controls with similar clinical baseline risk, but without progression, were analyzed. Index lesion mRNA transcripts were analyzed using NanoString technology. Random forest models were trained using panel gene sets to predict clinical endpoints and area under the curve (AUC), sensitivity, specificity, Youden index, and number needed to diagnose (NND) was measured. Survival probability was assessed with Kaplan–Meier estimator. Results All gene sets outperformed clinical parameters and predicted metastasis‐free and prostate cancer‐specific survival. However, there were significant differences between the panels. In metastasis prediction, the genes in Oncotype DX had inferior performance (area under the curve [AUC] = 0.65) compared to other panels (AUC = 0.73–0.74). Decipher, MSK‐IMPACT and Prolaris showed similar NND (2.83–3.12) with Oncotype DX having highest NND (4.79). In PCSD prediction, the Prolaris gene set performed worse (AUC = 0.66) than MSK‐IMPACT or Decipher (AUC = 0.72). Oncotype DX performed similarly to other panels (AUC = 0.69, p > .05). Oncotype DX demonstrated lowest NND (2.79) compared to other panels (4.22–5.66). Conclusion Transcript analysis of genes included in commercial panels is feasible in survival prediction of GG 2‐4 patients after radical prostatectomy and may aid in clinical decision making. There were significant differences between the panels, and overall stronger predictive gene sets are needed. Prospective investigation is warranted in biopsy materials.

Prognostic impact of kallikrein‐related peptidase transcript levels in prostate cancer

“…When KLKs and PARs were used as a panel with or without clinical parameters (GG, pathological stage and PSA), they improved classification of metastatic PCa and lethal disease. The demonstrated classification performance was similar to that of publicly available genes included in commercially available PCa risk stratification panels in our previous study 34 …”

“…The primary case‐control study for mRNA analyses consisted of 165 GG2‐4 patients treated by radical prostatectomy in Helsinki University Hospital in 1992‐2015. The selection process of patients has been previously described 34 . Seventy‐nine patients with metastatic progression or PCa‐specific death, during the median follow‐up of 11 years, were selected to present cases.…”

“…RNA extraction was performed using previously published methodology 34 . In brief, one to two 1 mm diameter punches were sampled from FFPE blocks.…”

“…The selection process of patients has been previously described. 34 Seventy-nine patients with metastatic progression or PCa-specific death, during the median followup of 11 years, were selected to present cases. Patients with similar clinical baseline characteristics, but no metastasis during the followup (n = 86), were assigned as controls, representing a clinically indolent phenotype of GG2-4 PCa.…”

Tissue- and Liquid-Based Biomarkers in Prostate Cancer Precision Medicine

“…Of the tissue-based biomarker tests discussed, Oncotype DX Prostate, ProMark, Decipher and Prolaris are the best validated thus far. While these tissue-based biomarker assays have the potential to influence the management of PC patients, there are a number of issues that are currently restricting their use: (i) Direct comparison of Oncotype DX, Prolaris and Decipher to one another has shown that prognostic outcomes can differ depending on the test used [ 353 , 354 ]. (ii) Many of these assays were developed and initially validated in cohorts of patients who were mostly white European or white American men, with limited initial research performed into the value of these tests in African American men, who are recognised as having poorer outcomes.…”