I-125 versus Pd-103 for low-risk prostate cancer: morbidity outcomes from a prospective randomized multicenter trial.

Abstract

The purpose of this study was to test the hypothesis that the shorter half-life of Pd-103 versus I-125 results in a shorter duration of radiation-related symptoms after prostate brachytherapy. As of February 2000, 110 of a planned total of 380 patients with 1997 American Joint Commission clinical stage T1c-T2a prostatic carcinoma (Gleason grade 2-6, prostate-specific antigen, 4-10 ng/mL) had been randomly assigned to implantation with I-125 (144 Gy, TG-43) or Pd-103 (125 Gy, NIST-99). Isotope implantation was performed by standard techniques, using a modified peripheral loading pattern. Treatment-related morbidity was monitored by mailed questionnaires, using standard American Urologic Association (AUA) and Radiation Therapy Oncology Group criteria at 1, 3, 6, 12, and 24 months. Use of alpha-blockers to relieve obstructive symptoms was not controlled for but was noted at each follow-up point. All patients reported here have a minimum 1-year follow-up. Randomization was carried out at a central enrollment office where eligibility criteria were confirmed and the patient assigned by computerized random number generator to one of the two treatment arms. Patients were assigned to 95 blocks of four. Most statistical comparisons shown here are by Student's unpaired t-test at specific follow-up times, as indicated in the figure legends. Additionally, considering the patients' scores change overtime, repeated measures were incorporated in a mixed model assuming an unstructured covariance matrix. Patients in each arm were well matched by preimplant prostate volume, AUA score, and age. The AUA scores peaked at the 1-month point for both isotopes and then gradually declined. The difference was greatest at 6 months, when I-125 patients had a mean AUA score of 16 (+/- 8), compared with 11 (+/- 10) for the Pd-103 patients. By 12 months, mean AUA scores for the Pd-103 patients had decreased to 12 (+/- 9), compared with 13 (+/- 8) for the I-125 patients. At 6 months after implantation, 41% of Pd-103 patients were still taking alpha-blockers, versus 44% of I-125 patients. The differences between isotopes were more marked in patients with a low pretreatment AUA score or smaller preimplant transrectal ultrasonography volume. Results of the mixed model, incorporating repeated measures for each patient, showed that the effect of isotope choice on AUA score depended on time. This effect was further dependent on baseline AUA score, but not on transrectal ultrasonography volume or on age. Urinary and rectal morbidity was generally low, typically grade 1 or 2. There was a trend to greater morbidity with I-125 than with Pd-103, most markedly at the 6-month time point. Patients treated with Pd-103 recovered from their radiation-induced prostatitis sooner than I-125 patients. It appears that patients with minimal pretreatment urinary obstructive symptoms are the most likely to experience implant-related exacerbations of their symptoms and are the most likely to benefit from the more rapid half-life of Pd-103 rather than I-125.