Anatomical Patterns of Recurrence Following Biochemical Relapse in the Dose Escalation Era of External Beam Radiotherapy for Prostate Cancer.

ABSTRACT

PURPOSE: We provide a comprehensive analysis of anatomical patterns of recurrence following external beam radiotherapy in patients with localized prostate cancer. MATERIALS AND METHODS: This retrospective analysis included 2,694 patients with localized prostate cancer who received definitive, dose escalated external beam radiotherapy from 1991 to 2008. First recurrence sites were defined as initial sites of clinically detected recurrence and any subsequent clinically detected recurrence within 3 months. Anatomical recurrence patterns were classified as local (prostate/seminal vesicles only), lymphotropic (lymph nodes only) and osteotropic (bones only) in patients with disease confined only to these respective sites for at least 2 years from the initial clinically detected recurrence. RESULTS: Prostate was the most common first recurrence site in the low, intermediate and high risk groups with an 8-year cumulative incidence of 3.5%, 9.8% and 14.6%, respectively. The 8-year risk of isolated pelvic lymph node relapse as the first recurrence site was 0%, 1.0% and 3.3%, respectively. In the 474 patients with clinically detected recurrence the most common first recurrence site was local in 55.3%, bone in 33.5%, pelvic lymph nodes in 21.3% and abdominal lymph nodes in 9.1%. Patients showed unique relapse distributions, including a pattern that was local in 41.6%, lymphotropic in 9.7%, osteotropic in 20.3% and multiorgan/visceral in 28.5%. Anatomical recurrence pattern was the strongest predictor of prostate cancer specific mortality on multivariate analysis of patients with clinically detected recurrence. CONCLUSIONS: The most common first recurrence site after dose escalated external beam radiotherapy for prostate cancer is in the prostate and seminal vesicles in all risk groups. In contrast, patients treated without elective pelvic lymph node irradiation are at relatively low risk for isolated pelvic lymph node relapse. Recurrence patterns revealed a tropism for specific anatomical distributions with divergent prognoses, suggesting underlying biological differences among tumors.