A retrospective analysis of patients with prostate cancer receiving primary treatment with either stereotactic body radiation therapy or intensity-modulated radiation therapy found that those receiving stereotactic body radiotherapy had greater rates of genitourinary toxicity during 2-year follow-up.
“The increased [genitourinary] toxicity was present at all time points and indicated an increase in both acute and later toxicity. This increase was largely associated with a higher rate of urethritis, urethral strictures, urinary incontinence, and obstruction among patients receiving [stereotactic body radiotherapy],” James B. Yu, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported in the Journal of Clinical Oncology.
Stereotactic body radiotherapy “is an innovative and aggressively marketed form of radiation therapy that is disseminating into national practice for the treatment of prostate cancer,” the authors wrote. The higher doses of radiation per treatment with stereotactic body radiotherapy can mean a shorter overall course of treatment, making it less expensive but more toxic, and the study was designed to compare both treatment costs and toxicity outcomes.
Using a national sample of Medicare beneficiaries age ≥ 66 years who received stereotactic body radiotherapy or intensity-modulated radiotherapy as primary treatment for prostate cancer from 2008 to 2011, the researchers identified 1,335 stereotactic body radiotherapy patients and 2,670 intensity-modulated radiotherapy patients. Each stereotactic body radiotherapy patient was matched to two intensity-modulated radiotherapy patients with similar follow-up (6, 12, or 24 months).
“In the 6 months after treatment initiation, 15.6% of [stereotactic body radiotherapy] vs 12.6% of [intensity-modulated radiotherapy] patients experienced [genitourinary] toxicity [odds ratio (OR) = 1.29; 95% confidence interval (CI) = 1.05–1.53; P = .009]. At 24 months after treatment initiation, 43.9% of [stereotactic body radiotherapy] vs 36.3% of [intensity-modulated radiotherapy] patients had [genitourinary] toxicity [OR = 1.38; 95% CI = 1.12–1.63; P = .001],” the researchers reported.
Patients receiving stereotactic body radiotherapy also had increased gastrointestinal toxicity at 6 months, with 5.8% having had a Medicare claim indicative of gastrointestinal toxicity vs 4.1% of intensity-modulated radiotherapy patients. But there was no difference in gastrointestinal toxicity in stereotactic body radiotherapy vs intensity-modulated radiotherapy patients at 12 or 24 months. There were no differences in any other toxicities at any of the study time points.
Mean treatment costs were $13,645 for stereotactic body radiotherapy and $21,023 for intensity-modulated radiotherapy, the researchers reported. For the two subcategories of complications (diagnostic procedures to investigate incontinence or obstruction, urethritis, urethral strictures, and bladder outlet obstructions), the mean cost was $145 for stereotactic body radiotherapy and $69 for intensity-modulated radiotherapy. For nonradiation cancer-related care, the mean costs were $2,963 in the year following stereotactic body radiotherapy and $1,978 for the year following intensity-modulated radiotherapy.
The researchers remarked:
Despite our finding of increased toxicity, it is still possible that [stereotactic body radiotherapy] may be preferable to [intensity-modulated radiotherapy] for both insurers and patients. Given that a late risk of fistula is a concern for [stereotactic body radiotherapy], it is important to note that we found no statistically significant difference in the incidence of fistulas between [intensity-modulated radiotherapy] and [stereotactic body radiotherapy] at any time point. First, [stereotactic body radiotherapy] is a more convenient treatment given its shorter treatment length. Second, we found that despite an increased cost of complications and medical care, [stereotactic body radiotherapy] was still less expensive than [intensity-modulated radiotherapy] overall. Third, [stereotactic body radiotherapy] may be more effective than [intensity-modulated radiotherapy] in terms of cancer cure and so may be preferable in the long-term when accounting for the morbidity of cancer recurrence.
Among the study limitations listed were inability to detect milder toxicities that did not require medical intervention and lack of toxicity grading and treatment-related information such as actual radiation doses and fields. The investigators also noted that stereotactic body radiotherapy technique may have improved since the years the patients in the study were treated (2008–2011), and a learning curve for stereotactic body radiotherapy may mean that direct clinical experience improved outcomes.
“Regardless, as radiation therapy techniques improve, and as practitioners become more experienced with [stereotactic body radiotherapy], the comparison between [stereotactic body radiotherapy] and [intensity-modulated radiotherapy] is a moving target,” the authors noted.
“It is important to recognize that Yu et al generate a testable hypothesis and not proof of causation because these results are nonrandomized and there are several patient and treatment factors that could have influenced the results,” Anthony V. D’Amico, MD, PhD, of Brigham and Women’s Hospital and Dana Farber Cancer Institute in Boston, wrote in an accompanying editorial.
Dr. D’Amico added that “despite the potential limitations of the study by Yu et al, including the lack of adjustment for important patient and treatment factors in the model and the inability to assess the grade of the [genitourinary] complications, the results of the current study should raise our awareness that the potential for an increase in clinically significant [genitourinary] toxicity with [stereotactic body radiotherapy] as compared with [intensity-modulated radiotherapy] exists.”
He also recommended that until the results of a Swedish randomized controlled trial evaluating the relative efficacy and toxicity of intensity-modulated radiotherapy vs an accelerated radiation treatment regimen are available, accelerated radiation therapy regimens using cyberknife or stereotactic body radiotherapy to treat prostate cancer “should only be performed in the setting of well-designed clinical trials.” ■
Yu JB, et al: J Clin Oncol 32:1195-1201, 2014.
D’Amico AV: J Clin Oncol 32:1183-1185, 2014.