Jordan A. Holmes, MD, MPH
Ronald C. Chen, MD, MPH
BRACHYTHERAPY HAS a long track record in treating cancer, dating back to the first reported use of an implanted radioactive source in 1901, and brachytherapy for the treatment of prostate cancer dates back to 1914, when Pasteu and Degrais used a radium source inserted through a urethral catheter. In 1917, the foundation for modern interstitial brachytherapy was established when Barringer first used radium needles inserted into the prostate through the perineum, using the guidance of a finger placed in the rectum.1 Thus, brachytherapy for prostate cancer has a 100-year track record. It remains one of the best ways—if not the best way—to deliver high doses of radiation to a well-defined target area, such as the prostate.
As summarized in the 2017 update of the ASCO/Cancer Care Ontario joint guideline on brachytherapy reported by Chin et al2—and reviewed in this issue of The ASCO Post—multiple randomized trials have demonstrated the efficacy of this treatment. RTOG 0232 has shown that in patients with low-risk to intermediate-risk prostate cancer, low-dose–rate brachytherapy alone provides essentially identical 5-year progression-free survival outcomes as low-dose–rate brachytherapy plus 5 weeks of external-beam radiation therapy.3 This trial provides level 1 evidence to support the use of low-dose–rate brachytherapy for patients with low-risk to favorable intermediate-risk prostate cancer. Compared with other radiation treatment options, brachytherapy is less costly,4,5 significantly less time-consuming for the patient (one outpatient procedure), and results in similarly favorable quality of life.6,7
For patients with high-intermediate or high-risk prostate cancer, the ASCENDE-RT randomized trial compared modern dose-escalated external beam radiation therapy to 78 Gy (8 weeks) vs 46 Gy (4.5 weeks) of external-beam radiation therapy plus low-dose–rate brachytherapy for an additional 115 Gy, with both arms receiving 1 year of androgen-deprivation therapy.8 Nine-year biochemical disease-free survival outcomes were dramatically different, favoring inclusion of brachytherapy (62% vs 83%). This finding is not surprising because brachytherapy delivers a significantly higher dose into the prostate than can be achieved safely with external-beam radiation therapy alone, and the results from this trial indicate this further dose escalation results in a significant increase in the number of patients who can be cured with radiation therapy.
Reasons for Declining Use of Brachytherapy
HOWEVER, IN THE PAST DECADE, use of brachytherapy for prostate cancer has sharply declined.9 The exact reason is unknown, but the decline may be multifactorial.10 Brachytherapy requires specialized equipment and expertise by the physician. It is also reimbursed less than long courses of external-beam radiation therapy.
“Compared with other radiation treatment options, brachytherapy is less costly, less time-consuming for the patient, and results in similarly favorable quality of life.”— Jordan A. Holmes, MD, MPH, and Ronald C. Chen, MD
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The decline in brachytherapy has also resulted in fewer cases for trainees; the median number of prostate brachytherapy procedures performed at academic and research-oriented facilities in 2012 was only six cases per year.11 This may be further compounded by the spread of self-referring “Uro-Rad” practices across the United States, which have decreased the numbers of prostate cancer patients treated at academic/training hospitals.12 The lack of radiation oncology graduates with sufficient brachytherapy training can feed into a cycle of fewer available physicians being comfortable to perform brachytherapy, even if randomized trials demonstrate it is an excellent option for patients and clinical practice guidelines recommend its use.2
Opportunity for Future Research
IT IS NOTABLE the ASCENDE-RT trial showed that adding brachytherapy was associated with increased urinary toxicity: the 5-year cumulative incidence of grade ≥ 3 urinary toxicity was 18.4% vs 5.2% for radiation therapy alone, whereas the prevalence of grade ≥ 3 urinary toxicity at 5 years was 8.6% vs 2.2%.13 However, other published series of combination external-beam radiation therapy with brachytherapy have reported much lower long-term toxicity rates.14,15 For example, Spratt et al reported on 870 patients with intermediate-risk prostate cancer treated with high-dose intensity-modulated radiation therapy with or without brachytherapy; they found the 7-year actuarial late grade ≥ 3 urinary toxicity was 3.1 vs 1.4%.14
These contrasting results reveal a significant opportunity for future research. Just as toxicity from external-beam radiation therapy has been clearly associated with doses delivered to organs such as the bladder and rectum, and research efforts to define “safe” dose levels to each organ have helped refine the planning and delivery of radiation therapy and thereby significantly reduce toxicity compared with the prior treatment era, a similar effort is needed for brachytherapy. Much more needs to be learned about safe dose levels for brachytherapy in the monotherapy setting and in combination with external-beam radiation therapy, so this effective and cost-effective treatment can be further improved for the benefit of patients. ■
DISCLOSURE: Drs. Holmes and Chen reported no conflicts of interest.
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2. Chin J, et al: Brachytherapy for patients with prostate cancer. J Clin Oncol 35:1737- 1743, 2017.
3. Prestidge BR, et al: Initial report of NRG Oncology/RTOG 0232. Int J Radiat Oncol Biol Phys 96:S4, 2016.
4. Hayes JH, et al: Observation versus initial treatment for men with localized, low-risk prostate cancer. Ann Intern Med 158:853- 860, 2013.
5. Wilson LS, et al: Cumulative cost pattern comparison of prostate cancer treatments. Cancer 109:518-527, 2007.
6. Chen RC, et al: Association between choice of radical prostatectomy, external beam radiotherapy, brachytherapy, or active surveillance and patient-reported quality of life among men with localized prostate cancer. JAMA 317:1141-1150, 2017.
7. Chen RC, et al: Individualizing quality-of-life outcomes reporting. J Clin Oncol 27:3916-3922, 2009.
8. Morris WJ, et al: Androgen suppression combined with elective nodal and dose escalated radiation therapy (the ASCENDE-RT Trial). Int J Radiat Oncol Biol Phys 98:275-285, 2017.
9. Martin JM, et al: The rise and fall of prostate brachytherapy. Cancer 120:2114-2121, 2014.
10. Orio PF 3rd, et al: The decreased use of brachytherapy boost for intermediate and high-risk prostate cancer despite evidence supporting its effectiveness. Brachytherapy 15:701-706, 2016.
11. Orio PF 3rd, et al: Prostate brachytherapy case volumes by academic and nonacademic practices. Int J Radiat Oncol Biol Phys 96:624-628, 2016.
12. Anscher MS, et al: The negative impact of stark law exemptions on graduate medical education and health care costs. Int J Radiat Oncol Biol Phys 76:1289-1294, 2010.
13. Rodda S, et al: ASCENDE-RT: An analysis of treatment-related morbidity for a randomized trial comparing a low-dose-rate brachytherapy boost with a dose-escalated external beam boost for high- and intermediate-risk prostate cancer. Int J Radiat Oncol Biol Phys 98:286-295, 2017.
14. Spratt DE, et al: Comparison of high-dose (86.4 Gy) IMRT vs combined brachytherapy plus IMRT for intermediate-risk prostate cancer. BJU Int 114:360-367, 2014.
15. Marshall RA, et al: Treatment outcomes and morbidity following definitive brachytherapy with or without external beam radiation for the treatment of localized prostate cancer: 20-year experience at Mount Sinai Medical Center. Urol Oncol 32:38.e1-38.e7, 2014.
Joseph Chin, MD
D. Andrew Loblaw, MD
AS REPORTED by Joseph Chin, MD, of London Health Sciences Centre, London, Ontario, and colleagues in the Journal of Clinical Oncology, ASCO and Clinical Care Ontario (CCO) have issued a joint update to the prior CCO guideline on use of...!-->!-->!-->!-->