Clinical Investigation
Customized Dose Prescription for Permanent Prostate Brachytherapy: Insights From a Multicenter Analysis of Dosimetry Outcomes

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Purpose

To investigate the biochemical control rate in patients undergoing permanent prostate brachytherapy as a function of the biologically effective dose (BED) and risk group.

Methods and Materials

Six centers provided data on 3,928 permanent brachytherapy patients with postimplant dosimetry results. The mean prostate-specific antigen level was 8.9 ng/mL. 125I was used in 2,293 (58%), 103Pd in 1,635, and supplemental external beam radiotherapy in 882 (22.5%) patients. The patients were stratified into low- (n = 2,188), intermediate- (n = 1,188), and high- (n = 552) risk groups and into three BED groups of < 140 Gy (n = 524), 140–200 Gy (n = 2284), and >200 Gy (n = 1,115). Freedom from biochemical disease progression (biochemical freedom from failure [bFFF]) was determined using the American Society for Therapeutic Radiology Oncology and Phoenix definitions and calculated using the Kaplan-Meier method, with factors compared using the log–rank test.

Results

The 10-year prostate-specific antigen bFFF rate for the American Society for Therapeutic Radiology Oncology and Phoenix definitions was 79.2% and 70%, respectively. The corresponding bFFF rates for the low-, intermediate-, and high-risk groups was 84.1% and 78.1%, 76.8% and 63.6%, and 64.4% and 58.2%, respectively (p < 0.0001). The corresponding bFFF rate for the three BED groups was 56.1% and 41.4%, 80% and 77.9%, and 91.1% and 82.9% (p < 0.0001). The corresponding bFFF rate for the low-risk patients by dose group was 69.8% and 49.8%, 86% and 85.2%, and 88.1% and 88.3% for the low-, intermediate, and high-dose group, respectively (p <0.0001). The corresponding bFFF rate for the intermediate-risk patients by dose group was 52.9% and 23.1%, 74.1% and 77.7%, and 94.3% and 88.8% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001). The corresponding bFFF rate for high-risk patients by dose group was 19.2% and 41.7%, 61.8% and 53.2%, and 90% and 69.6% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001).

Conclusions

These data suggest that permanent brachytherapy dose prescriptions can be customized to risk status. In low-risk patients, achieving a BED of ≥140 Gy might be adequate for prostate-specific antigen control. However, high-risk disease might require a BED dose of ≥200 Gy.

Introduction

Permanent prostate brachytherapy can be performed using different isotopes and in combination with hormonal therapy (HT) or external beam radiotherapy (EBRT). Controversy exists regarding the selection of the optimal regimen for a given risk group. For low-risk patients, monotherapy using 125I with a prescription dose of 144 Gy or 103Pd with a dose of 124 Gy has been advocated (1). Intermediate- and high-risk disease is often treated with the addition of HT and/or EBRT. Despite these general guidelines, several single-institution studies have found little or no benefit with additional therapies compared with monotherapy 2, 3. In addition, the dosing recommendations have come into question. Some centers have routinely prescribed 160 Gy when using 125I and others 144 Gy 4, 5, 6. Other brachytherapy sites exclusively use 103Pd, believing that a radiobiologic advantage may exist for 124 Gy of this isotope in most clinical situations (7). Finally, the most appropriate dose for combination therapy (implantation plus EBRT) has come into question, prompting a randomized trial investigating different dosing regimens (8).

We elected to try and answer some of these difficult questions by analyzing the results of six large and experienced brachytherapy centers. Because each center used their own treatment protocols involving different dosing regimens, isotopes, and indications for the addition of HT and EBRT, a common dose variable that equated the results from all the centers was chosen. Stock et al. (9) have identified that the biologically effective dose (BED) is one method to equate the different isotopes, doses, and the addition of EBRT.

In this study, we investigated whether a BED could be identified to correspond to disease risk that could be tailored to the patient's risk status.

Section snippets

Methods and Materials

Six centers provided clinical data from 5,889 consecutively treated permanent brachytherapy patients, of whom 3,928 had postimplant dosimetry results. The institutional review board at each center approved the sharing of their raw patient data, which was entered into the Prostate Research Database (created by Fearn and Potters), an Access-based database with a corresponding data export and biochemical outcome calculator. No center analyzed the outcomes independent of the entire cohort.

125I was

Results

The median censored follow-up time was 42.5 months (range, 1.8–161). The median PSA level was 8.9 ng/mL (range, 0–300). The mean number of follow-up PSA values per patient was 6.3 (range, 2–22).

The 10-year bFFF rate for the entire cohort was 79.2% and 70% using the ASTRO-Kattan and Phoenix definitions, respectively. The corresponding bFFF rate by risk group was 84.1% and 78.1%, 76.8% and 63.6%, and 64.4% and 58.2% for the low-, intermediate, and high-risk groups, respectively (p < 0.0001). The

Discussion

This study represents a large cohort of prostate brachytherapy patients with postimplant dosimetry and a long follow-up period. This analysis has demonstrated the importance of implant dosimetry in predicting for biochemical freedom from recurrence for all risk groups of patients. Furthermore, our results suggest that the implant dose can be customized according to the prostate cancer disease risk status.

Patients who present with low-risk disease require intermediate-dose prescriptions (BED

Conclusions

The data from six large prostate brachytherapy centers have suggested that radiation doses can be prescribed based on disease characteristics. Low-risk patients demonstrated excellent bFFF at doses that have typically been recommended in published studies (140 Gy for 125I and 124 Gy for 103Pd) and did not seem to benefit from high doses of 125I (≥189 Gy or 103Pd ≥167 Gy). According to our results, patients with intermediate- and high-risk disease have improved bFFF when treated with doses

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