Can aggressive prostatic carcinomas be identified and can their natural history be altered by treatment?

The factors that determine tumor aggressiveness are multifactorial: age, stage, and grade. Even a well differentiated tumor in a young patient may be aggressive someday because of genetic drift and tumor heterogeneity. In a recent review of 826 favorably selected cases managed with conservative therapy, metastatic disease had developed in 19% with grade I tumors, 42% with grade II, and 74% with grade III at 10 years. Recognizing that <20% of men present with grade I disease, most prostate cancers are a threat to life in men who are going to live longer than 10 years. On the other hand, some tumors at presentation are too far advanced to cure. To improve the accuracy of preoperative staging in identifying these cases, we have developed nomograms based upon clinical stage, grade, and serum prostate-specific antigen (PSA). Traditionally, patients with high-grade tumors (Gleason 8-10) were never considered candidates for radical prostatectomy because of their poor expectancy for long-term survival. However, with improvements in the staging of prostate cancer and with a reduction in the morbidity of radical prostatectomy, a subset of these patients are potential candidates for curative therapy. We have recently studied the clinical outcome of 72 men with Gleason scores of 8-10 on needle biopsies who presented with clinically localized disease (9 T1c, 22 T2a, 17 T2b, 13 T2c, and 11 T3a). Of the 63 men who underwent radical prostatectomy, 46 (68%) had negative lymph nodes; nine did not undergo surgery because of positive lymph nodes identified from frozen section. The actuarial likelihood of an undetectable serum PSA at 5 years was 43% for men with negative lymph nodes and 45% for men with organ-confined disease. Thus, with proper evaluation, some men with even the most aggressive tumors can be cured by surgery if their pelvic lymph nodes are negative.