Clinical Investigation
High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

This work was presented at the World Congress of Brachytherapy, Barcelona, Spain, May 10-12, 2012.
https://doi.org/10.1016/j.ijrobp.2012.07.004Get rights and content

Purpose

To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer.

Methods and Materials

Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy, using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3.

Results

The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported.

Conclusion

Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.

Introduction

In patients with clinically localized prostate cancer, permanent low-dose-rate (LDR) brachytherapy (BRT) 1, 2, external beam radiation therapy (EBRT) (3), and interstitial (IRT) high-dose-rate (HDR) BRT as boost to EBRT (4) are commonly used treatment options. These modalities have shown biochemical control rates comparable to those in patients treated with radical prostatectomy 5, 6. However, in the absence of randomized clinical trials of sufficient size, the optimal radiotherapeutic approach remains controversial.

Clinical evidence shows that EBRT dose escalation for organ-confined prostate cancer improves local disease control 3, 7. It is therefore reasonable to assume that improvements might also be made using HDR-BRT. Also, on the basis of radiobiological data, prostate cancer seems to have a low a/β ratio (ie, 1.2-3.0 Gy) 8, 9, 10, indicating high sensitivity to large fractions. This may allow biological dose escalation using hypofractionated regimens. IRT-HDR-BRT is an effective way of achieving dose escalation with active shaping of the dose distribution by accurately controlling the radiation source position and modulating source dwell times. This permits anatomy-based dose optimization without unacceptable changes in dosimetry caused by source migration and tissue deformity, as can be the case with LDR BRT (11). Only a few studies have described HDR monotherapy for prostate cancer 12, 13, 14, 15, 16, 17, 18, 19, 20. The objective of our study was to report our experience with IRT-HDR-BRT as monotherapy for clinically localized prostate cancer.

Section snippets

Patients and procedures

Between January 2002 and December 2009, a total of 718 consecutive patients were treated with IRT-HDR-BRT as monotherapy for clinically localized prostate cancer. All patients had histologically proven disease and were staged according to American Joint Committee on Cancer, sixth edition, staging guidelines. Pretreatment staging included digital rectal examination, transrectal ultrasound (TRUS) and, if indicated, CT and/or magnetic resonance imaging (MRI), and bone scintigraphy. Treatment

Clinical outcome

Of 718 patients, 35 (4.9%) patients developed biochemical relapses, and 9 patients eventually showed evidence of metastatic disease. Survival and BC results for all patients are shown in Figure1a. BC at 36 months by treatment group was 98%, 98%, and 95% for Groups A, B, and C, respectively (P=.08, Fig. 1b). BC by treatment group at 60 months was 97% and 94% for Groups A and B, respectively Fig. 1b. BC at 60 months was 95%, 93%, and 93% for low-, intermediate-, and high-risk patients,

Discussion

Long-term results from our study demonstrate that IRT-HDR-BRT is an effective monotherapy for locally confined prostate cancer. Constant and reproducible clinical outcomes were achieved with 3 dose fractionation regimens. Even though direct comparisons are difficult, given varying clinical expertise of practitioners and a variety of definitions of risk, our results of 90% actuarial BC and 97% MFS are promising, confirming clinical outcomes reported by other authors (Table 5). Martinez et al (12)

Conclusions

The findings of our study demonstrate HDR-BRT is a safe and effective monotherapy for patients with clinically localized prostate cancer. Constant and reproducible clinical outcomes were generated with three treatment regimens, achieving an overall actuarial BC and MFS rate of 90% and 97%, respectively. We can also conclude that TRUS-guided implantation with 3D treatment planning and anatomy-based dose optimization provide reliable prospective dosimetry and precise treatment delivery ensuring

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This work was supported in part by an investigator-initiated research grant from Nucletron BV, Veenendaal, The Netherlands.

Conflict of interest: none.

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