What is the optimal dose for 125I prostate implants? A dose-response analysis of biochemical control, posttreatment prostate biopsies, and long-term urinary symptoms

PURPOSE: To define the optimal dose for 125I prostate implants by correlating post implant CT dosimetry findings with urinary symptoms, biochemical failure, and posttreatment biopsies. METHODS AND MATERIALS: Patients with T1-T2, Gleason score 2-6 prostate cancer treated with I-125 brachytherapy were analyzed. Group 1 (276 patients) was observed from 18 to 108 months (median, 34 months) and had urinary symptoms prospectively assessed using the International Prostate Symptom Score (IPSS) system. Group 2 (181 patients) observed from 24 to 108 months (median, 44 months) and did not receive hormonal therapy. Implant dose was defined as the D90 (dose delivered to 90% of the prostate on a dose-volume histogram). Patients were analyzed by dose categories: <140 Gy, 140 to <160 Gy, 160 to <180 Gy, and > or =180 Gy. In Group 1, the mean pre- to postimplant IPSS scores were compared in different dose categories by using a matched paired t test. In Group 2, the effect of dose on biochemical control was tested with actuarial methods by using the American Society for Therapeutic Radiology and Oncology definition and on local control with posttreatment biopsies (113 patients). RESULTS: A comparison of pre- with postimplant IPSS revealed no significant changes in scores in the dose groups <180 Gy except for small changes in urgency and bladder emptying in the dose group <140 Gy. In dose group >180 Gy, mean scores changed from 0.5 to 1.0 (p=0.002) for emptying, 0.76 to 1.29 (p=0.004) for weak stream, 0.24 to 0.51 (p=0.009) for straining, 1.55 to 1.82 (p=0.05) for nocturia, and 6.3 to 8.45 (p=0.0009) for the total score. Freedom from biochemical failure (FFBF) at 5 years was 68% for doses <140 Gy, 97% for 140 to <160 Gy, 98% for 160 to <180 Gy, and 95% for > or =180 Gy (p=0.0025). Overall, patients with doses <140 Gy (median follow-up, 66 months) had an FFBF of 68%, compared with 96% for patients with doses > or =140 Gy (median follow-up, 35 months; p=0.0002). Multivariate analysis found dose to be the most significant factor affecting FFBF. Positive biopsies were found in 23% for doses <140 Gy, 21% for 140 to <160 Gy, 10% for 160 to <180 Gy, and 8% for > or =180 Gy. Overall, biopsies were positive in 22% for doses <160 Gy vs. 9% for > or =160 Gy (p=0.05). CONCLUSIONS: Optimal 125I prostate implants should deliver a D90 of 140-180 Gy, on the basis of postimplant dosimetry. Doses of <140 Gy are associated with increased biochemical failure, and doses >180 Gy with a small increase in long-term urinary symptoms.