Dose Escalation for Prostate Cancer Using the Three-Dimensional Conformal Dynamic Arc Technique: Analysis of 542 Consecutive Patients

Purpose

To present the results of dose escalation using three-dimensional conformal dynamic arc radiotherapy (3D-ART) for prostate cancer.

Methods and Materials

Five hundred and forty two T1-T3N0M0 prostate cancer patients were treated with 3D-ART. Dose escalation (from 76 Gy/38 fractions to 80 Gy/40 fractions) was introduced in September 2003; 32% of patients received 80 Gy. In 366 patients, androgen deprivation was added to 3D-ART. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median follow-up was 25 months.

Results

Acute toxicity included rectal (G1-2 28.9%; G3 0.5%) and urinary events (G1-2 57.9%; G3-4 2.4%). Late toxicity included rectal (G1-2 15.8%; G3-4 3.1%) and urinary events (G1-2 26.9%; G3-4 1.6%). Two-year failure-free survival and overall survival rates were 94.1% and 97.9%, respectively. Poor prognostic group (GS, iPSA, T), transurethral prostate resection, and dose >76 Gy showed significant association to high risk of progression in multivariate analysis (p = 0.014, p = 0.045, and p = 0.04, respectively). The negative effect of dose >76 Gy was not observed (p = 0.10), when the analysis was limited to 353 patients treated after September 2003 (when dose escalation was introduced). Higher dose was not associated with higher late toxicity.

Conclusions

Three-dimensional-ART is a feasible modality allowing for dose escalation (no increase in toxicity has been observed with higher doses). However, the dose increase from 76 to 80 Gy was not associated with better tumor outcome. Further investigation is warranted for better understanding of the dose effect for prostate cancer.

Introduction

Radiotherapy dose escalation over 70 Gy improves both biochemical and clinical local control in prostate cancer 1, 2, 3, 4, 5, 6, 7, 8. However, one of the limitations of high-dose radiotherapy is the potential increase in both acute and late toxicity 9, 10, 11, 12, 13, 14, 15. The optimal choice of beam configuration for prostate cancer remains unclear. Historically, a four-field box technique has been used, allowing only moderate dose escalation (≤ 70 Gy). More recently other approaches have been widely applied, including the use of conformal three-, five-, and six-field techniques. New modalities such as noncoplanar radiotherapy (16), intensity modulated radiotherapy (IMRT) 17, 18, 19, and arcing techniques 20, 21, 22, 23 have been introduced. The availability of technological advances in treatment planning and execution has renewed the interest in the rotational radiotherapy techniques 21, 22, 23 with its potential advantages in dose distribution. Intensity modulated arc therapy (IMAT) 24, 25 and CyberKnife with noncoplanar nonisocentric arc radiotherapy (26) have been developed.

In our department prostate cancer patients were treated until 2002 with three-dimensional (3D) conformal six-coplanar static field radiotherapy, and the results of this treatment have been reported previously 11, 27. In 2002, we introduced 3D conformal two-dynamic arc therapy (3D-ART) to facilitate dose escalation. Our previous study comparing the dose distribution for 3D conformal six-field and two-dynamic arc techniques showed that both of them offer good dose distribution for planning target volume with significantly better sparing of the rectum and urinary bladder for 3D-ART (28). In 2003, dose escalation was introduced aiming at 80 Gy in 40 fractions (the dose usually prescribed with the six-field technique was 76 Gy in 38 fractions). The aim of this study is to report the preliminary clinical outcome of 3D-ART in terms of toxicity and efficacy in a large series of patients treated at one institution within a period of 4 years.