The correlation between D90 and outcome for I-125 seed implant monotherapy for localised prostate cancer

Abstract

Background and purpose: In 1998 Stock and Stone demonstrated a dose response relationship correlating D90 with probability of biochemical control and showed that a D90 of 140 Gy is a highly significant factor in predicting PSA relapse free survival (PSA-RFS). Although, a mean D90 of over 140 Gy was achieved in our series, there is nevertheless a normal distribution with 20% of patients achieving a D90 of less than 120 Gy. We have analysed the possible causes for the low D90 and the impact on outcome.

Patients and methods: Prospective data from 667 patients treated between 1995 and 2001 by I-125 seeds prostate implant as monotherapy were analysed. Post-implant dosimetry was performed on 413 patients. D90 and other indices were calculated for each patient. Statistical analysis was performed on D90 dose to identify the correlation that would predict the 8.2 years PSA relapse free survival as defined by the American Society for Therapeutic Radiology and Oncology (ASTRO).

Results: Correlation between D90 and outcome shows no significant difference for the whole population between those who receive greater or less than 140 Gy (P=0.43) and there was also no difference for those receiving more or less than 130 Gy (P=0.14). Subgroup analysis by risk group, however, showed that for low risk patients there was a significant correlation between D90 and PSA control (P<0.01). Although, post-implant dosimetry was performed 6-8 weeks after brachytherapy, post-implant CT still showed variable levels of oedema compared with the pre-implant ultrasound. A statistically significant relationship was shown between D90 and the ratio between CT and ultrasound volume (P<0.01) which suggests that some low D90s may be related to persistent oedema at the time of calculation. Segmental analysis of a subgroup of 32 patients showed that the dose was most often deficient in the anterior basal segment of the gland.

Conclusions: D90 was found to be a good discriminator for those with low risk where failure to achieve local control is likely to be the dominant cause of PSA failure. No significant dose response relationship between D90 and PSA was found in the intermediate and high-risk population of patients. This could be due to (1) the presence of oedema or discrepancy between pre- and post-implant volumes causing a low D90, (2) the possibility that the underdosed area could be situated where there is unlikely to be tumour, (3) the fact that biochemical control does not equate to local control because some patients fail outside the prostate, particularly in the high and intermediate risk patients, (4) if D90 is a good discriminator only for low risk patients, the absence of a dose response correlation in this series which contained 53.8% intermediate and high risk patients could be related to case mix.