Prognostic Validity of DNA Karyometry in Prostate Cancer Patients under Active Surveillance

The option of active surveillance for patients with localized prostate cancer depends on a low Gleason score (GS) of 6. Nevertheless, about 30% of patients face clinical progression within five years. Our objective was to prove the superior prognostic validity of DNA karyometry to predict non-progression of prostate cancer patients under active surveillance.

Our hypothesis is that automated measurements of the DNA content of prostate cancer cells produce a DNA grade of malignancy that is much more accurate than the subjective GS in predicting non-progression of prostate cancers. Nuclear DNA measurements of cancer tissue in the residual biopsy material of 80 patients from the HAROW (hormones, active surveillance, radiation, operation, watchful waiting) study were taken. GSs were determined by local pathologists and a reference pathologist. A 4.1 year follow-up included repeated prostate-specific antigen (PSA) values, the number and GSs of positive biopsies, determination of the clinical stage, and in 19 cases the results of prostatectomies.

Reproducibility of the GSs was 55% without differentiation between stages 6 and 7a and 45% with differentiation between stages 6 and 7a. Progression occurred in 37.5% of patients if an upgrade of any inclusion criterion was used as evidence and in 18.8% of patients if only PSA doubling time (DT) of <36 months or upstaging to stage pT3 was used as evidence. The prevalence of DNA grade 1 was 40%. Sensitivity, specificity, and negative predictive value of local pathologists’ GSs, the reference pathologist’s GSs, and DNA karyometry were 0%, 95.0%, and 74.0%; 20.0%, 86.7%, and 76.5%; and 85.0%, 51.0%, and 90.6% if an upgrade of any inclusion criterion was used as evidence of progression and 5.9%, 96.8%, and 79.2%; 23.5%, 87.3%, and 80.9%; and 100%, 50.8%, and 100% if only a PSA DT of <36 months and/or upstaging to stage pT3 were used. Therefore, compared to subjective Gleason scoring, objective automated DNA karyometry can considerably more consistently rule out the advancement of prostate malignancies under active surveillance (AS) within four years.

For the subjective microscopic GS but 100% for objective DNA karyometry, the chance of excluding objectively determined advancement of an untreated, localised prostate cancer under AS was only 80.9 %. Therefore, this conservative, non-invasive therapeutic approach is significantly more secure for patients with a DNA grade of malignancy of 1.