Clinical Investigation
Natural History of Clinically Staged Low- and Intermediate-Risk Prostate Cancer Treated With Monotherapeutic Permanent Interstitial Brachytherapy

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Purpose

To evaluate the natural history of clinically staged low- and intermediate-risk prostate cancer treated with permanent interstitial seed implants as monotherapy.

Methods and Materials

Between April 1995 and May 2005, 463 patients with clinically localized prostate cancer underwent brachytherapy as the sole definitive treatment. Men who received supplemental external beam radiotherapy or androgen deprivation therapy were excluded. Dosimetric implant quality was determined based on the minimum dose that covered 90% of the target volume and the volume of the prostate gland receiving 100% of the prescribed dose. Multiple parameters were evaluated as predictors of treatment outcomes.

Results

The 12-year biochemical progression-free survival (bPFS), cause-specific survival, and overall survival rates for the entire cohort were 97.1%, 99.7%, and 75.4%, respectively. Only pretreatment prostate-specific antigen level, percent positive biopsy cores, and minimum dose that covered 90% of the target volume were significant predictors of biochemical recurrence. The bPFS, cause-specific survival, and overall survival rates were 97.4%, 99.6%, and 76.2%, respectively, for low-risk patients and 96.4%, 100%, and 74.0%, respectively, for intermediate-risk patients. The bPFS rate was 98.8% for low-risk patients with high-quality implants versus 92.1% for those with less adequate implants (p < 0.01), and it was 98.3% for intermediate-risk patients with high-quality implants versus 86.4% for those with less adequate implants (p < 0.01).

Conclusions

High-quality brachytherapy implants as monotherapy can provide excellent outcomes for men with clinically staged low- and intermediate-risk prostate cancer. For these men, a high-quality implant can achieve results comparable to high-quality surgery in the most favorable pathologically staged patient subgroups.

Introduction

Permanent interstitial seed implants are used commonly as monotherapy for men with low-risk, clinically localized prostate cancer. Brachytherapy is used somewhat less frequently as the sole modality for men with intermediate-risk disease. In the larger series the biochemical progression-free survival (bPFS) rate ranges from 80% to 98% for low-risk patients 1, 2, 3, 4, 5, 6, 7, 8 undergoing brachytherapy and from 70% to 97% for intermediate-risk patients 1, 2, 3, 5, 6, 7, 8, 9. However, many men in these series received supplemental external beam radiation and/or neoadjuvant or planned adjuvant androgen deprivation. These series also included men whose implants would be considered suboptimal by today's standards.

The purpose of this report is to explore the natural history of prostate cancer in men who receive brachytherapy as the sole modality. There are obvious short-term advantages to avoiding initial combined-modality treatment, including shorter duration of treatment, exposure to fewer side effects, and lower overall health care costs. However, these advantages disappear rapidly if a significant number of men treated with monotherapy require additional, increasingly morbid salvage therapy because of disease recurrence. Hence understanding the efficacy and durability of high-quality, sole-modality brachytherapy is important.

Section snippets

Methods and Materials

Between April 1995 and May 2005, 463 patients with low- or intermediate-risk prostate cancer were treated with permanent interstitial seed implants as the sole definitive treatment. Men who received neoadjuvant or planned adjuvant androgen suppression for any reason were excluded from the analysis. In addition, men who received supplemental external beam radiotherapy were excluded. Patients were categorized as low risk if they met all of the following criteria: Gleason score of 6 or less,

Results

Table 1 summarizes the clinical and treatment characteristics of men included in the analysis. Of the 463 men, 319 were low risk and 144 were intermediate risk. In addition to having a higher Gleason score, men in the intermediate-risk group had a higher pretreatment PSA level, higher percentage of positive biopsy cores, and higher clinical stage and were older.

At 12 years, the bPFS, CSS, and OS rates for the group as a whole were 97.1%, 99.7%, and 75.4%, respectively (Fig. 1). Table 2 presents

Discussion

The largest published series to date of sole-modality brachytherapy includes 1,444 low-risk men and 960 intermediate-risk men from 11 institutions (8). The 8-year PSA relapse-free survival rate was 82% for low-risk patients and 70% for intermediate-risk patients. Unfortunately, dosimetric analysis was available for only a subset of this cohort. In the cases when dosimetry information was available, men whose 125I implants had a D90 of 130 Gy or greater (still below current recommendations) (15)

Conclusions

Disease recurrence is very uncommon in clinically staged low- and intermediate-risk prostate cancer patients treated with high-quality brachytherapy monotherapy. For these men, a high-quality implant can achieve results comparable to high-quality surgery in the most favorable pathologically staged patient subgroups. As brachytherapy implant techniques continue to improve and the importance of appropriate dosimetric target coverage continues to disseminate, these results should become

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