Shorter Course of SBRT Proves Safe, Effective in High-Risk Prostate Cancer

Article

January 27, 2021 — A shorter course of stereotactic body radiotherapy has been shown to have encouraging efficacy with favorable toxicity when used in patients with high-risk prostate cancer in a multi-institutional, international setting.

Amar U. Kishan, MD

A shorter course of stereotactic body radiotherapy (SBRT) has been shown to have encouraging efficacy with favorable toxicity when used in patients with high-risk prostate cancer in a multi-institutional, international setting, according to findings from a study published in the International Journal of Radiation Oncology, Biology, Physics.1

Led by investigators at the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center, the study found that SBRT, which delivers higher doses of radiation therapy over the course of 5 or fewer treatments, is safe and as effective as the standard 45-day course of radiation therapy in this patient population.2 However, further prospective studies are needed to determine the optimal dose and target volume of SBRT in these patients.

“These findings suggest that SBRT, which condenses radiation treatment for prostate cancer into as few as 4-5 sessions (as compared with 20-45 sessions previously), is safe and effective in a broad setting for patients with high-risk prostate cancer,” lead study author Amar U. Kishan, MD, an assistant professor of radiation oncology at the David Geffen School of Medicine at UCLA and researcher at the UCLA Jonsson Comprehensive Cancer Center, told OncLive. “This has previously been shown in patients with low- and intermediate-risk prostate cancer but extending these findings to [those with] high-risk prostate cancer broadens applicability [of this approach].”

SBRT can be considered for patients with high-risk prostate cancer, as long as they have social or medical hardships that prevent longer courses of radiation therapy, according to 2020 National Comprehensive Cancer Network guidelines. However, guidelines issued by the European Association of Urology are less supportive of this. 

The latter note that the major evidence to support ultra-hypofractionation for this patient population is based on data yielded from a subset of 126 patients who were enrolled to the randomized phase 3 HYPO-RT-PC trial (ISRCTN45905321). Participants did not receive concurrent androgen deprivation therapy (ADT), which is now considered a standard of care for patients with high-risk disease receiving definitive radiotherapy. The authors of that trial concluded that their general conclusions of oncologic equivalency may not be applicable to patients with high-risk prostate cancer. Other published prospective data supporting SBRT for this patient population are limited.

Earlier research led by investigators at UCLA provided significant evidence that a shortened regimen of radiation therapy could be a feasible treatment option for patients with low- and intermediate-risk prostate cancer.3 Investigators decided to broaden this study to see whether a shorter treatment course of radiation could be used in patients with more aggressive disease.

For this research, investigators collected patient-level data from 7 institutions with phase 2 studies and prospective databases. Data were pooled for a total of 344 patients with a minimum follow-up of 24 months. Biochemical recurrence-free survival (BCRFS) and distant metastasis-free survival (DMFS) were estimated using a Kaplan-Meier framework, while Fine and Gray competing risk and Cox proportional hazards regression models were created to evaluate the association between time to biochemical recurrence (BCR) and time to distant metastasis and prespecified variables of interest. Logistic regression models were developed to evaluate associations between acute and late grade 2 or higher genitourinary and gastrointestinal and a priori determined variables, like age, dose per fraction, ADT use, and nodal radiotherapy.

The median follow-up on the study was 49.5 months (range, 35.8-61.9). Seventy-two percent of patients (n = 248) received ADT, with a median duration of 9 months. Results showed that the estimated BCRFS and DMFS rates at 4 years were 81.7% (95% CI, 77.2%-86.5%) and 89.1% (95% CI, 85.3%-93.1%), respectively. Seventeen percent of patients (n = 59) had a BCR and 8% (n = 26) experienced distant metastases.

Multivariable competing risk analyses revealed that 7 Grey (Gy) per fraction versus 8 Gy per fraction was significantly linked with increased risk of BCR (subdistribution HR [sHR], 2.15; 95% CI, 1.07-4.32; P = .03), as was natural log initial prostate-specific antigen (sHR, 1.42; 95% CI, 1.0-1.08; P = .02). Additionally, investigators did not observe any significant predictors of time to distant metastases.

Cause-specific models showed comparable results with regard to BCR and distant metastases. Here, a 1-year increase in age at treatment was found to be significantly linked with increased BCR risk (HR, 1.04; 95% CI, 1-1.07; P = .035).

BCRFS was found to be significantly greater in the patients who received ADT (log-rank P = .009), although no significant difference was observed with DMFS (log-rank P = .097). The cumulative incidence of BCR was observed to be substantially lower in the patients who received ADT (P value, .017 per Gray’s test), while the cumulative incidence of distant metastases was not different (P value, 0.36 per Gray’s test). 

Regarding safety, acute grade 2 or greater genitourinary (GU) toxicity was reported in 18% of patients, while 5% of patients experienced gastrointestinal (GI) effects. No acute grade 3 or higher GU or GI effects were observed. Notably, a dose per fraction of 7 Gy was linked with lower odds of acute grade 2 or higher GU toxicity, while a dose per fraction of 8 Gy was associated with higher odds of this toxicity (odds ratio [OR], 0.09; 95% CI, 0.02-0.48; P = .005).

The 4-year cumulative incidence estimate for late grade 2 or higher GU toxicity was 17.6% (95% CI, 13.6%-21.9%), while this estimate was 6.4% (95% CI, 3.7%-10.1%) for GI toxicity.

Moreover, the crude incidences of late grade 3 or higher GU toxicity was 2.3% versus 0.9% for GI toxicity, with a median time to onset of 21 months and 22 months, respectively.

Although the results of this study highlight the efficacy of this approach, and overall toxicity rates were low and consistent with prior data with SBRT in patients with low- and intermediate-risk disease, the study still had limitations. For one, this analysis focused on multiple single- arm phase 2 studies and prospective registries. Due to the non-randomized nature of the study, this research cannot provide level I evidence to support SBRT for use in this patient population. 

The ongoing randomized PACE-C trial is expected to provide additional level 1 evidence concerning the efficacy of SBRT vs conventional radiotherapy among patients with HRPCa.

“There are several intriguing avenues [for future exploration]. First and foremost, large randomized trials, such as PACE-C run out of the United Kingdom, will be critical to cement SBRT as the standard option, as opposed to a standard option, so we eagerly await that,” Kishan told OncLive. “Second, multiple ongoing studies are [being done] to find out how we can best optimize treatment in patients with more aggressive features, perhaps by adding drugs or selectively increasing the dose, and de-escalating treatments in patients with less aggressive features. Third, technological advances, such as direct magnetic resonance imaging–guided radiotherapy, may help us improve the precision of this treatment further and [this is] being actively studied.”

References

  1. van Dams R, Jiang NY, Fuller, DB, et al. Stereotactic body radiotherapy for high-risk localized CARcinoma of the prostate (SHARP) consortium: analysis of 344 prospectively treated patients. Int J Radiat Oncol Biol Phys. Published online January 22, 2021. doi:10.1016/j.ijrobp.2021.01.016
  2. Study finds shorter radiation regimen safe, effective for men with advanced prostate cancer. News release. UCLA Health. January 25, 2021. Accessed January 26, 2021. http://bit.ly/3cfs4MM.
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