Low-Dose-Rate Brachytherapy for Low- and Intermediate-Risk Prostate Cancer: A Dose-Response Analysis for 3392 Consecutive 125-Iodine Monotherapy Patients

William James Morris, MD, FRCPC, Ingrid Spadinger, PhD, FCCPM, Ross Halperin, MD, FRCPC
PP05 Presentation Time: 9:36 AM

Purpose

To investigate the effect of D90 on biochemical failure in a large consecutive cohort of 125-Iodine monotherapy patients.

Materials and Methods

Between 07/1998 and 09/2011, 3436 men with NCCN low- and intermediate-risk prostate cancer underwent 125-Iodine monotherapy, 3392 (98.6%) of whom had post-implant, CT-based dose metrics recorded. Sixty percent had intermediate-risk disease and 46% had 6 months of neoadjuvant/concomitant androgen deprivation therapy (ADT). The median D90 was 153 Gy (mean 154 Gy, SD 15.9, range 86.5-223 Gy). The median follow up was 5.48 years (mean 6.12, SD 3.95, range 0-16.9); 648 men have been followed for at least 10 years.

Results

As of 09/2015, there have been 222 biochemical relapse events (nadir+2ng/mL threshold) yielding 5- and 10-year K-M biochemical progression free survival (b-PFS) estimates of 94.9% (±1.0%) and 89.9% (±1.6%) respectively. Intermediate-risk patients were more than twice as likely to experience biochemical failure compared to low-risk (HR 2.13, p <0.001). In a multivariate Cox model, Gleason sum 7 versus ≤6 (HR 2.2, p <0.001), pre-treatment PSA (HR 1.14 per unit increase, p <0.001) and clinical T2b-c versus T1c-T2a (HR 1.8, p <0.001) were each strongly associated with increased risk of biochemical failure. The use of ADT reduced the risk of biochemical failure (HR 0.51, p <0.001). Post-implant D90 values, age and percent positive cores were not statistically associated with biochemical relapse in MVA. Although not reaching statistical significance, a small dose effect was identified when comparing the annualized risk of relapse for years 4-9 post-implant permitting a quantitative estimate of the impact of D90 on b-PFS. For intermediate-risk patients who did not receive ADT (N =929), D90 had no measurable impact on the risk of biochemical failure. However, for the intermediate-risk patients who did receive ADT (N =1085), there was a 1.8% improvement in the 10-year b-PFS for each 10 Gy increase in D90. For the low-risk patients, there was a 1.4% improvement in the 10-year b-PFS for each 10 Gy increase in D90.

Conclusions

The three conventional prognostic factors (Gleason sum, pre-treatment PSA and clinical T-Stage) as well as the use of ADT were all strongly associated with biochemical failure in MVA. D90 did not reach statistical significance in MVA, but a small beneficial effect of increased D90 values was identified.