Grading Evolution and Contemporary Prognostic Biomarkers of Clinically Significant Prostate Cancer

Abstract

Gleason grading remains the strongest prognostic parameter in localized prostate adenocarcinoma. We have here outlined the evolution and contemporary practices in pathological evaluation of prostate tissue samples for Gleason score and Grade group. The state of more observer-independent grading methods with the aid of artificial intelligence is also reviewed. Additionally, we conducted a systematic review of biomarkers that hold promise in adding independent prognostic or predictive value on top of clinical parameters, Grade group and PSA. We especially focused on hard end points during the follow-up, i.e., occurrence of metastasis, disease-specific mortality and overall mortality. In peripheral blood, biopsy-detected prostate cancer or in surgical specimens, we can conclude that there are more than sixty biomarkers that have been shown to have independent prognostic significance when adjusted to conventional risk assessment or grouping. Our search brought up some known putative markers and panels, as expected. Also, the synthesis in the systematic review indicated markers that ought to be further studied as part of prospective trials and in well characterized patient cohorts in order to increase the resolution of the current clinico-pathological prognostic factors.

Keywords: Gleason grading; biomarker; grade grouping; prostate cancer; survival.

Figure 1

PRISMA diagram of the systematic review. MVA = Multivariable analysis.

Figure 2

Future prospect of a multimodal diagnostic work-up and treatment decision-making. ¹: Prostate-specific antigen (PSA) is unspecific at the diagnostic phase and should be taken only as part of an informed risk assessment or based on recommendations for personalized screening. ²: Current evidence does not support any biomarkers. Further research is needed to implement biomarkers to clinical practice (as discussed in text).