Morphologic and clinical significance of multifocal prostate cancers in radical prostatectomy specimens

To examine the histologic details of small, independent cancers compared with the largest (index) tumor and their impact on prostate-specific antigen (PSA) failure in 486 men treated only by radical retropubic prostatectomy (RRP).

The tumor volume and percentage of Gleason grade 4/5 carcinoma were recorded in 3-mm step sections. Univariate statistics were calculated for the largest, total (largest plus smaller cancers), and smaller tumor volumes, number of independent foci, patient age, and follow-up. Cox hazards model determined the relative importance of all variables in relation to failure.

The mean index tumor volume was 4.16 cm3; smaller cancer volumes averaged 0.63 cm3. The index cancer volume was gaussian in distribution; smaller tumor volumes were highly skewed toward 234 carcinomas less than 0.5 cm3. Only 17% of all cases had one carcinoma. The Cox model showed similar hazard rates of PSA failure for both the index (3.43) and the total cancer (3.74) volumes. The hazard rate for the presence of any Gleason grade 4/5 carcinoma was 6.5. As the numbers of smaller tumors increased, the PSA cure rates improved.

The PSA failure rates (hazard ratios) were similar for the index tumor and the index plus smaller cancers, confirming that predictive estimates only need to measure the largest carcinoma. The greater the number of lesser cancers, the smaller the size of the index cancer. The extraordinary multiplicity of these small independent cancers in 3-mm step sections may explain the poor correlation between six or more biopsies with the index cancer in radical prostatectomy specimens.