Dedifferentiation of locally recurrent prostate cancer after radiation therapy. Evidence for tumor progression

Background. Untreated or unsuccessfully treated prostatic adenocarcinoma may develop more malignant characteristics as time passes-the phenomenon of tumor progression. Whether this occurs after unsuccessful radiation therapy has not been answered. This study was designed to address that issue. Methods. The histologic grades at initial diagnosis and at local recurrence were compared in 49 patients who experienced local recurrence after external beam radiation therapy. Results. Tumor grades were assigned using the M. D. Anderson grading system. At the initial diagnosis, the grades were distributed as follows: Grade 1, 18 (37%), Grade 2, 22 (45%); Grade 3, 8 (16%); and Grade 4, 1 (2%). At recurrence, the grades were: Grade 1, 3 (6%); Grade 2, 14 (29%); Grade 3, 14 (29%); and Grade 4, 18 (37%). The shift to higher grades at recurrence was highly significant (P < 0.001). This dedifferentiation could not be accounted for by possible tissue sampling variability, and stepwise multiple variable logistic regression revealed that the only factor predicting for dedifferentiation was the time since treatment. The tumors that recurred later had a significantly higher likelihood to be dedifferentiated than those that recurred early. Patients whose tumors dedifferentiated had a poorer survival than those whose tumors retained their original grade. Conclusions. The possibilities were considered that the dedifferentiation could arise by tissue sampling error, by persistence and regrowth of high-grade components, by the development of new tumors, or by radiation-induced transformation. None of these mechanisms appeared to explain the data adequately, and it was concluded that the observed dedifferentiation was indeed a manifestation of time-dependent tumor progression. Eradication of the primary tumor is therefore important, not only to allay local symptoms, but also to prevent the emergence of more virulent and potentially lethal tumors.