Clinical investigation
Prostate
15-Year biochemical relapse free survival in clinical Stage T1-T3 prostate cancer following combined external beam radiotherapy and brachytherapy; Seattle experience

https://doi.org/10.1016/j.ijrobp.2006.07.1382Get rights and content

Purpose: Long-term biochemical relapse-free survival (BRFS) rates in patients with clinical Stages T1-T3 prostate cancer continue to be scrutinized after treatment with external beam radiation therapy and brachytherapy.

Methods and Materials: We report 15-year BRFS rates on 223 patients with clinically localized prostate cancer that were consecutively treated with I125 or Pd 103 brachytherapy after 45-Gy neoadjuvant EBRT. Multivariate regression analysis was used to create a pretreatment clinical prognostic risk model using a modified American Society for Therapeutic Radiology and Oncology consensus definition (two consecutive serum prostate-specific antigen rises) as the outcome. Gleason scoring was performed by the pathologists at a community hospital. Time to biochemical failure was calculated and compared by using Kaplan-Meier plots.

Results: Fifteen-year BRFS for the entire treatment group was 74%. BRFS using the Memorial Sloan-Kettering risk cohort analysis (95% confidence interval): low risk, 88%, intermediate risk 80%, and high risk 53%. Grouping by the risk classification described by D’Amico, the BRFS was: low risk 85.8%, intermediate risk 80.3%, and high risk 67.8% (p = 0.002).

Conclusions: I125 or Pd103 brachytherapy combined with supplemental EBRT results in excellent 15-year biochemical control. Different risk group classification schemes lead to different BRFS results in the high-risk group cohorts.

Introduction

Prostate brachytherapy continues to be a first-line treatment option for men with clinical stage T1-T2 prostate cancer. Technical advances are regularly reported, including the use of transrectal ultrasound guidance for preplanned or intraoperatively planned implants (1, 2, 3). Postimplant dosimetry has led to improved prostate coverage and a better understanding of the tolerances of adjacent critical structures (4). Data from the retropubic era showed that those patients with B1 (T2a) disease who received “adequate” implant dosimetry (based on orthogonal X-rays) achieved disease control rates similar to radical prostatectomy and external beam radiation therapy (EBRT) patients from that era (5). Improved implant quality has been demonstrated to result in better biochemical relapse-free survival (BRFS) outcomes in several modern studies (6, 7, 8).

Today’s improved patient selection and improved implant quality has resulted in multiple brachytherapy reports demonstrating 5–10 year BRFS rates are equivalent to the best published radical prostatectomy and three-dimensional conformal radiation therapy results (8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21). We report the Seattle 15-year results of transperineal interstitial permanent prostate brachytherapy combined with moderate-dose neoadjuvant EBRT in a group of consecutively treated and prospectively followed patients with clinical T1-T3 prostate cancer.

Section snippets

Methods and materials

This is a prospective cohort study. Between January 1987 and December 1993, 232 patients presenting with clinically localized prostate cancer were consecutively treated with I125/Pd103 brachytherapy with neoadjuvant EBRT.

Seven patients did not meet the initial cohort criteria for inclusion because of androgen ablation therapy for downsizing purposes and 1 patient had inadequate follow-up, reducing the analytic cohort to 223. Median follow-up time was 9.43 years ranging from 0.62 to 17.07 years.

Results

The clinical status at presentation is outlined in Table 1. The mean pretreatment PSA was 15.25 ng/mL, 63.3% of patients presented with T2b-T3 disease by DRE, and 35% had Gleason score 7-10. There were seven local failures (3.1%) based on a positive biopsy, or positive DRE, or androgen ablation therapy for suspected local recurrence.

The Kaplan-Meier BRFS for the entire study group is 74%, as depicted in Fig. 1. The BRFS by biopsy Gleason score, initial PSA, and clinical stage are shown in Fig. 2

Discussion

We report the 15-year BRFS results of 223 consecutively treated clinical T1-T3 prostate cancer patients. Patients were treated with 45 Gy EBRT followed a few weeks later by a transperineal template-guided transrectal ultrasound-guided permanent interstitial implant with I125 or Pd103 radioactive seeds. None of these patients received hormonal therapy. The neoadjuvant EBRT was given because the authors felt these patients were at significant risk for extracapsular or seminal vesicle disease

Conclusion

The 15-year BRFS outcomes with neoadjuvant EBRT and I125/Pd103 boost continue to show excellent long-term disease control rates despite a relatively unfavorable patient population, older era of treatment, and less sophisticated EBRT and brachytherapy techniques than are available.

Acknowledgments

The authors would like to thank Jonathan Khanjian for assisting in the preparation of this manuscript.

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