Presentation Authors: Emily Vertosick, New York, NY, Stephen Zappala, Andover, MA, Sanoj Punnen, Miami, FL, Jonas Hugosson, Gothenburg, Sweden, Stephen Boorjian, Rochester, MN, Alexander Hease, Hamburg, Germany, Peter Carroll, Mathew Cooperberg, San Francisco, CA, Anders Bjartell, Malmo, Sweden, Hans Lilja, Andrew Vickers*, New York, NY
Introduction: Prostate volume is a strong predictor of prostate biopsy outcome, but requires an additional procedure (transrectal ultrasound [TRUS] or MRI) and is thus generally not included in biopsy prediction models. The four kallikrein panel - commercially available as the 4Kscore - is widely used to predict the risk of high grade (Gleason grade group [GGG] 2+) disease and requires only a blood draw. As volume measurements may be available for some men - such as those with prior negative biopsies or on active surveillance - we aimed to assess whether adding prostate volume to the 4kscore would improve discrimination for GGG2+ disease.
Methods: 9,131 patients with available prostate volume from TRUS and total PSA â‰¤ 25 ng/ml from 9 research cohorts were included in this analysis, including 5 historical cohorts (sextant biopsy, pre-ISUP 2005 grading) and 4 contemporary cohorts (10+ cores, ISUP 2005 grading). Previously published models were used to predict risk of GGG2+ based on the kallikrein panel. The difference in discrimination between the kallikrein panel and kallikrein panel + volume models was calculated for each cohort and entered into a meta-analysis.
Results: Increased prostate volume was found to be associated with a significantly lower risk of GGG2+ disease after controlling for kallikrein panel score in 6 out of 9 cohorts, but volume did not add discrimination. The meta-analytic estimate of discrimination of 0.817 (95% CI 0.802, 0.831) for the kallikrein panel was not improved after including prostate volume (difference in AUC -0.003, 95% CI -0.015, 0.009). There was significant heterogeneity (p=0.002) driven by an increase in AUC in a cohort of academic centers (0.044, 95% CI 0.022, 0.066). No increase in AUC was seen in any other cohort and there was no evidence of heterogeneity after exclusion of academic centers(p=0.7). In a sensitivity analysis, addition of prostate volume to the kallikrein panel resulted in a nonsignificant increase in AUC in the academic centers cohort (0.012, 95% CI -0.032, 0.055).
Conclusions: Our results do not justify the inclusion of prostate volume in the four kallikrein panel. The markers in the kallikrein panel provide a non-invasive approach to assessing risk of high-grade prostate cancer. There is some evidence that specialist centers can measure volume in an informative way, and further research is needed in this area.
Source of Funding: This work was supported in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center [P30 CA008748], a SPORE grant in Prostate Cancer to Dr. H. Scher [P50-CA9