Cleveland Clinic Study Favors Brachytherapy in Treating Prostate Cancer

Efficacy similar to IMRT with less toxicity

Despite the increasing use of external beam radiation therapy (EBRT) for the treatment of prostate cancer nationwide, brachytherapy is at least as effective and is less toxic, according to Cleveland Clinic researchers. Brachytherapy is also far less costly.

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A recent study reported long-term efficacy and toxicity for a cohort of 1,989 Cleveland Clinic patients, with data accrued between 1996 and 2007. The cohort was treated with low-dose-rate prostate brachytherapy permanent implant (PI) monotherapy without external beam radiation.

Researchers found the therapy effective for low-risk and low-intermediate-risk prostate cancer, and observed that it appears to be effective for high-intermediate-risk and high-risk prostate cancer as well, although sample sizes for the last two categories were limited.

Overall, significant long-term toxicities were rare when brachytherapy was performed as monotherapy, according to study results.

“I don’t know that it’s going to change practice patterns,” says co-author Jay P. Ciezki, MD, a radiation oncologist at Cleveland Clinic. “I hope it argues in favor of this therapy.”

Brachytherapy procedure more demanding, not as lucrative

Despite the favorable data, brachytherapy is still in decline. “There is a tremendous financial incentive to not do brachytherapy,” Dr. Ciezki says. A study in the Journal of Clinical Oncology (Feb.9,2015) found IMRT to be the most expensive therapy, with an average lifetime cost of $48,699, while brachytherapy cost less than active surveillance. Also, permanent implant is a technically demanding procedure, and like all surgeries, requires practice, whereas with intensity modulated radiation therapy (IMRT), “dexterity has no impact on outcome,” he says.

The Cleveland Clinic study, Long-Term Efficacy and Toxicity of Low-Dose-Rate (125)I Prostate Brachytherapy as Monotherapy in Low-, Intermediate-, and High-Risk Prostate Cancer, appeared in a recent issue of the International Journal of Radiation Oncology, Biology, Physics. It is based on data accrual from prostate cancer cases since the beginning of brachytherapy treatment at Cleveland Clinic. Physicians in the Department of Radiation Oncology and the Department of Urology have monitored outcomes and toxicity and compared the outcomes of IMRT, brachytherapy and prostatectomy through the inception cohort study and biannual program review meetings.

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Prostate cancer remains the most commonly diagnosed non-skin malignancy in American men and, despite earlier detection and advances in treatment, it is still the second-leading cancer-related cause of death, according to the study.

Inception cohort study offers unique perspective

Researchers report that approximately 80 percent of patients with new diagnoses present with clinically localized disease, but no clear consensus exists on the best method of treating localized prostate cancer that maximizes the chance for cure while minimizing toxicity. This is in large part because randomized controlled trials are difficult to conduct in this disease, mainly due to its long natural history, well-established referral patterns and strong patient preferences regarding treatment options.

Brachytherapy’s efficacy in controlling disease in the Cleveland Clinic study was consistent with other large published series, many of which, unlike the Cleveland Clinic study, included supplemental EBRT for a substantial proportion of patients and mandated androgen deprivation therapy for intermediate-risk and high-risk patients, or both.

The median age of patients in the Clinic study was 67 years, and the median overall and prostate-specific antigen follow-up times were 6.8 years and 5.8 years, respectively. The overall 5-year rates for biochemical relapse-free survival, distant metastasis-free survival, overall survival and prostate cancer-specific mortality were 91.9%, 97.8%, 93.7% and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%, 76.1% and 2.5%, respectively. [Abstract: Results]

Genitourinary (GU) and gastrointestinal (GI) toxicities were equivalent to or lower than those reported in studies using EBRT. The Cleveland Clinic study’s observed rate of overall grade ≥3 late GU toxicity was similar to that published in other large series, say the authors, and those studies that include patients treated with supplemental EBRT reported a higher rate of late toxicity. The rate of late GI toxicity was lower than that which Cleveland Clinic had previously reported for EBRT, and lower than that reported in other institutions’ series with combination therapy.

Androgen deprivation therapy (ADT) did not appear to provide additional benefit compared with PI alone. A relatively low percentage of patients (18.2 percent) received ADT, despite being treated without EBRT.

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Promising therapy for high-risk patients

“The thing that’s a little bit unusual here, and something we’re actually completing another manuscript about, is the high-risk patient population,” says Dr. Ciezki. “That is a population that not very many people would do brachytherapy for… [although] we’ve been doing high-risk patients for some time.”

Patients have other options besides brachytherapy and EBRT for the treatment of clinically localized prostate cancer, including radical prostatectomy and ADT. Costs of those four modalities vary widely. According to a 2013 Georgetown University study of urologists’ IMRT use, the mean estimated cost for prostatectomy or brachytherapy is about $17,000, compared with IMRT, which is about $32,000. ADT is about $2,112.

And yet, use of IMRT is growing, partly due to physicians’ self-referral of patients. The Georgetown study, funded by the American Society for Radiation Oncology, found that urologists who acquired ownership of IMRT services increased their use of IMRT substantially more than those who did not own such services. Self-referral is generally illegal, but is permitted in this case as an “in-office ancillary service,” Dr. Ciezki says.

Cleveland Clinic provides no financial incentive for physicians to choose one treatment over another.

Petereit DG et al. Where have you gone, brachytherapy? Journal of Clinical Oncology. Published online Feb. 9, 2015, doi:10.1200/JCO2014.59.8128.

Photo ©Russell Lee