DOSE ESCALATION WITH THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY AFFECTS THE OUTCOME IN PROSTATE CANCER

Abstract Purpose: Three-dimensional conformal radiation therapy (3D-CRT) is a technique designed to deliver prescribed radiation doses to localized tumors with high precision, while effectively excluding the surrounding normal tissues. It facilitates tumor dose escalation which should overcome the relative resistance of tumor clonogens to conventional radiation dose levels. The present study was undertaken to test this hypothesis in patients with clinically localized prostate cancer. Methods and Materials: A total of 743 patients with clinically localized prostate cancer were treated with 3D-CRT. As part of a phase I study, the tumor target dose was increased from 64.8 to 81 Gy in increments of 5.4 Gy. Tumor response was evaluated by post-treatment decrease of serum prostate-specific antigen (PSA) to levels of ≤1.0 ng/ml and by sextant prostate biopsies performed ≥2.5 years after completion of 3D-CRT. PSA relapse-free survival was used to evaluate long-term outcome. The median follow-up was 3 years (range: 1–7.6 years). Results: Induction of an initial clinical response was dose-dependent, with 90% of patients receiving 75.6 or 81.0 Gy achieving a PSA nadir ≤1.0 ng compared with 76% and 56% for those treated with 70.2 Gy and 64.8 Gy, respectively ( p p p p Conclusions: The data provide evidence for a significant effect of dose escalation on the response of human prostate cancer to irradiation and defines new standards for curative radiotherapy in this disease.