Re-evaluating the concept of 'dominant/index tumor nodule' in multifocal prostate cancer

Prostate cancer (PCa) often presents as a multifocal disease with heterogeneity in Gleason score (GS) and genetic alterations. Dominant/index tumor nodule (DN), the largest nodule in a multifocal disease, is presumed to harbor the most aggressive biological behavior and therefore dictate the overall clinical behavior of PCa. In this study, we examined the pathological features of DN and re-evaluated the validity of the "DN" concept in multifocal PCa. A total of 201 consecutive radical prostatectomy specimens were totally submitted and examined. All independent cancer foci were recorded with prognostically important pathological parameters. Unifocal and multifocal disease was present in 25 (12.4 %) and 176 (87.6 %) cases, respectively. In 20 (11.3 %) multifocal cases, the highest GS, the largest tumor volume (TV), and extraprostatic extension (EPE) did not concur in the same tumor nodules. Non-DNs had a higher GS and EPE in 13 cases each and had both the highest GS and EPE in 5 cases. In the majority of multifocal prostate cancer (88.7 %), DNs have the highest GS and EPE. In these cases, DN is still a valid concept and can be used for assigning overall GS and procuring tissue for research. However, in a significant number of cases (11.3 %), the largest TV, the highest GS, and EPE did not concur in the same tumor nodules. In these cases, pathologists should de-emphasize the concept of DN. Instead, they should place the emphasis on the multifocal nature of the disease and document the pathological features of all independent tumor foci that have the largest TV, the highest GS, and EPE.