Elsevier

Brachytherapy

Volume 9, Issue 1, January–March 2010, Pages 27-35
Brachytherapy

High-dose-rate brachytherapy in combination with conformal external beam radiotherapy in the treatment of prostate cancer

https://doi.org/10.1016/j.brachy.2009.04.007Get rights and content

Abstract

Purpose

To report long-term outcomes for treatment of prostate cancer using dose escalation with high-dose-rate (HDR) brachytherapy and 3-dimensional conformal external beam radiotherapy (3DCRT), and compare them with outcomes for treatment of prostate cancer with 3DCRT alone at the same institution.

Methods and Materials

From 1998 to 2003, 587 patients were treated for clinically localized prostate cancer. Patients received either 3DCRT (median, 46 Gy) with a single HDR brachytherapy implant (196 patients) delivering a fractionated dose of 18 Gy (combined group) or 3DCRT (median, 70 Gy; 387 patients; “3DCRT alone”). There were 41.9% patients with intermediate-risk and 42.6% with high-risk disease. In all, 441 patients (75.1%) received neoadjuvant and 116 patients (19.8%) received adjuvant androgen deprivation therapy. The American Society of Therapeutic Radiology and Oncology Phoenix definition for biochemical failure was used.

Results

The median followup was 5.5 years. The 5- and 7-year biochemical control (BC) rates were 82.5% and 80.3%, respectively, for the combined group and 81.3% and 71%, respectively, for 3DCRT alone; for overall survival, they were 91.9% and 89.5% vs. 88.7% and 86.2%, respectively, whereas for cause-specific survival, they were 96.9% and 96.1% vs. 97.6% and 96.2%, respectively. Cox proportional hazard regression analysis for BC revealed that low Gleason grade, HDR brachytherapy combined with 3DCRT, and adjuvant androgen deprivation therapy were significant in predicting BC. Radiation Therapy Oncology Group Grade 3 late urinary and rectal morbidity rates were 7.1% and 0%, respectively. No Grade ≥4 reactions were detected.

Conclusions

HDR brachytherapy combined with 3DCRT was associated with improved BC and minimal toxicity in patients with unfavorable prostate cancer compared with conventional 3DCRT.

Introduction

Radiotherapy (RT) has an established role as a curative treatment modality in localized prostate cancer. Dose escalation with 3-dimensional conformal external beam radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT) improves outcome with acceptable toxicity profiles [1], [2]. Results from two randomized controlled trials [3], [4] and single-institutional reports of high-dose-rate (HDR) brachytherapy in combination with 3DCRT demonstrate an alternative technique for dose escalation, with tumor control rates similar to those obtained with 3DCRT alone (Table 1). HDR brachytherapy in combination with 3DCRT allows the delivery of a highly conformal radiation treatment, and compared with 3DCRT, it has the potential advantages of delivering dose with greater accuracy and overcoming the problem of organ movement [11], [12]. Other advantages of HDR brachytherapy are the rapid dose falloff and ability to optimize dose distribution by varying source dwell times along the catheters (13). This potentially allows for greater sparing of rectum and bladder than is achievable with external beam radiation alone (11). Finally, the possibility of a low α:β ratio for prostate cancer provides a radiobiologic advantage for hypofractionated RT [14], [15].

Although results from Phase III studies demonstrate long-term efficacy of combined treatment [3], [4], there is significant heterogeneity in treatment technique, dose, fractionation, use of androgen deprivation, and patient characteristics. Other potential disadvantages of HDR brachytherapy include the invasiveness of the procedure, the specialized skills, and resources needed. The purpose of this study was to report the outcomes of men treated with HDR brachytherapy for dose escalation in combination with 3DCRT, and compare them with men treated contemporaneously with 3DCRT alone.

Section snippets

Patients

We reviewed 587 consecutive patients treated for prostate cancer between July 1, 1998, and December 31, 2003. Patients provided informed consent for data collection, analysis, and aggregated reporting, and hospital ethics approval was obtained before data analysis. In all, 196 men (33.4%) received combined HDR brachytherapy and 3DCRT (the combined group) and 391 (66.6%) were treated with 3DCRT alone. All patients had biopsy-proven adenocarcinoma reported using the Gleason system but without

Patient characteristics

The median follow-up time for all 587 patients was 5.5 years (interquartile range, 4.2–7 years; 90th percentile, 8.1 years). Table 2 summarizes the patient characteristics. Patients in the combined group were significantly younger at diagnosis, presented with a higher iPSA, and were more frequently in a high-risk group: 50% in the combined group compared with 39% in the 3DCRT alone group (p < 0.001). The use of neoadjuvant ADT was also more common. Twenty-eight patients treated with HDR

Discussion

This study evaluates the use of HDR brachytherapy and 3DCRT for dose escalation, compared with 3DCRT alone, in terms of BC for localized prostate cancer. Strength of this study is the long median follow-up of 5.5 years, allowing 7-year estimates showing no difference in BC or survival between treatment groups. Patients treated with HDR brachytherapy in combination with 3DCRT presented with a higher percentage of unfavorable prognostic factors relative to the external beam group, and on

Conclusion

This retrospective, single-institutional study demonstrated that HDR brachytherapy may be used safely in achieving dose escalation combined with 3DCRT for localized prostate cancer. For the convenience of patients, treatment time was shortened with the potential for improving therapeutic ratio by hypofractionation (13). On multivariable analysis, the combined treatment was associated with a statistically significant improved BC when compared with standard external beam RT adjusting for adverse

Acknowledgments

The authors gratefully acknowledge the important contribution of Karen Scott, Data Management.

References (36)

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Supported in part by the Peter Grant Hay Fund.

Presented in part at the 2008 World Congress of Brachytherapy, Boston, MA, May 4–6, 2008.

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