Context.—: Multifocal prostate cancer at radical prostatectomy (RP) may be graded with assessment of each individual tumor nodule (TN) or global grading of all TNs in aggregate.
Objective.—: To assess case-level grade variability between these 2 grading approaches.
Design.—: We reviewed 776 RPs with multifocal prostate cancer with 2 or more separate TNs of different Grade Groups (GGs). Two separate grades were assigned to each RP: one based on the TN with the highest grade and a global grade based on the Gleason pattern volumes for all TNs. We then compared the results of these 2 methods.
Results.—: The case-level grade changed by 1 or more GGs between the 2 grading methods in 35% (132 of 374) of GG3 through GG5 cases. Twelve percent (37 of 309) of GG2 cases with Gleason pattern 4 of more than 5% based on individual TN grading decreased their Gleason pattern 4 to less than 5% based on the global approach. Minor tertiary pattern 5 (Gleason pattern 5 <5%) was observed in 6.8% (11 of 161) of GG4 (Gleason score 3 + 5 = 8 and 5 + 3 = 8) and GG5 cases with global grading. The risk of grade discrepancy between the 2 methods was associated with the highest-grade TN volume (inverse relationship), patient age, and number of TNs (P < .001, P = .003, and P < .001, respectively).
Conclusions.—: The global grading approach resulted in a lower grade in 35% of GG3 through GG5 cases compared with grading based on the highest-grade TN. Two significant risk factors for this discrepancy with a global grading approach occur when the highest-grade TN has a relatively small tumor volume and with a higher number of TNs per RP. The observed grade variability between the 2 grading schemes most likely limits the interchangeability of post-RP multi-institutional databases if those institutions use different grading approaches.