DNA-cytometric grading of prostate cancer systematic review with descriptive data analysis

Gleason-score <=6, assessed on core needle biopsies, is an essential prognostic parameter to offer the strategy of Active Surveillance (AS) to patients with locally confined cancers of the prostate. Yet, its interobserver reproducibility is low (48-70%) and its prognostic validity unsatisfactory. An option to complementary assess the malignant potential of these cancers are objective DNA-ploidy-measurements on existing biopsies. For that purpose chromosomal heterogeneity is indirectly quantified by DNA-cytometry resulting in DNA-grades of malignancy 1-4. This review systematically trawls and evaluates all scientific publications on the potential diagnostic and prognostic validity and the heterogeneity of DNA-ploidy measurements in cancers of the prostate between 1966 and 2013. Publications have been classified into Oxford levels of evidence and levels of significance were given for the correlation of DNA-ploidy with different clinical outcomes. 114 scientific articles had to be excluded because of different methodological reasons. All but one of the 67 methodologically acceptable articles report on a significant diagnostic resp. prognostic significance of DNA ploidy measurements in cancers of the prostate. 8 level 1b studies report that DNA-ploidy, assessed on punch biopsies independently predicts organ confinement as assessed after radical prostatectomy. 18 level 2b studies prove that DNA-ploidy measurements add statistically significant information to the Gleason-score. 16 level 2b investigations report a significant correlation of DNA-ploidy with recurrence-free survival. 15 level 2b studies document a significant correlation with overall survival after different types of therapy. 5 level 2b investigations prove a significant correlation with local recurrence or progress after radical prostatectomy. 3 level 2b publications show a significant correlation of DNAploidy with the occurrence of lymph nodeor bone metastases after radical prostatectomy. 1 level 2b study documents the additional prognostic value of DNA-ploidy measurements over conventional subjective grading in prostate cancer patients under AS. All existing 15 narrative reviews on selected articles dealing with prognostic DNA-cytometry in cancers of the prostate are in favor of this method. Prospective level 1b studies, especially those proving the validity of DNA ploidy measurements to predict non-progression in patients with clinically insignificant low-grade low stage cancers of the prostate eligible for Active Surveillance additionally to the Gleason-score are still missing.