Can radical prostatectomy alter the progression of poorly differentiated prostate cancer?

A favorable outcome after radical prostatectomy for early stage prostate cancer has sometimes been attributed to the relatively benign natural history of the disease rather than the beneficial effects of treatment. Poorly differentiated tumors, however, are recognized as inherently aggressive and progress rapidly when managed conservatively. We determined the actuarial rate of treatment failure after radical prostatectomy for clinically localized (stages T1 to T3) poorly differentiated cancer, using as an end point an increase in the serum level of prostate specific antigen (PSA) to assess whether treatment altered the rapid progression expected of these cancers. Of 500 patients treated with radical prostatectomy, regardless of grade, the actuarial nonprogression rate was 76 +/- 5% at 5 years and 73 +/- 6% at 10 years. Poorly differentiated cancer, defined as Gleason score 7 or greater in the radical prostatectomy specimen, was present in 268 patients (54%) who had a nonprogression rate at 5 years of 55 +/- 12% compared to 92 +/- 4% for the 232 patients with a well or moderately differentiated (Gleason score less than 7) cancer (p < 0.00005). The extent of the cancer (confined or not confined) was strongly associated with progression (p < 0.00005). Only 76 of the 268 poorly differentiated tumors (28%) were confined to the prostate and the prognosis was excellent. At 5 years 85 +/- 18% of the patients had no evidence of progression, compared to 46 +/- 12% with poorly differentiated cancer extending outside the gland (p < 0.0001). In a multivariate analysis neither the grade nor volume of the tumor influenced the rate of progression when the cancer was confined to the prostate. Impalpable tumors detected by an elevated PSA level were as likely to be poorly differentiated as palpable disease (56% versus 63%) but were significantly more likely to be confined to the prostate (44% versus 24%, p < 0.01). Poorly differentiated cancers usually extend outside of the prostate by the time they are detected, and they progress rapidly. PSA increases the detection of impalpable high grade cancer confined to the gland. When these tumors are detected while still confined, most can be controlled by radical prostatectomy.