Cancer volume and site of origin of adenocarcinoma in the prostate: relationship to local and distant spread.

Biologic aggressive behavior in adenocarcinoma of the prostate is proposed to be a direct function of cancer volume. In an autopsy series, distant metastasis was found only in cancers that had both volume greater than 5 cc and areas of poor differentiation (Gleason grades 4 and 5). In subsequent study of over 200 radical prostatectomy specimens, cancers were found to originate both in the peripheral zone (PZ) and in the normally small anteromedial transition zone (TZ) where benign nodular hyperplasia also develops. Anatomic TZ and PZ cancers were nearly equivalent to clinical stage A and B cancers, respectively. Transition zone cancers showed much less capsule penetration and seminal vesicle invasion than PZ cancers of comparable volume because the TZ boundary provided a barrier to cancer spread through the PZ. In PZ carcinomas, capsule penetration depended largely on facilitated spread along perineural spaces, and its distribution was determined by the location of superior and inferior nerve pedicles. Capsule penetration, seminal vesicle invasion, and positive surgical margins were all strongly correlated with cancer volume. Tumors smaller than 4 cc had all morphologic variables favorable; tumors larger than 12 cc tended to have all variables unfavorable. Lymph node metastasis in radical prostatectomy cases was most strongly predicted by a combination of cancer volume plus percentage of high-grade tumor. Cancers with more than 3.2 cc of grade 4 and/or 5 component showed a 100-fold increase in proportion of cases with nodal spread.