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Stereotactic Body Radiotherapy for Localized Prostate Cancer
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Whether stereotactic body radiotherapy (SBRT) is noninferior to conventionally or moderately hypofractionated regimens with respect to biochemical or clinical failure in patients with localized prostate cancer is unclear.
METHODS
We conducted a phase 3, international, open-label, randomized, controlled trial. Men with stage T1 or T2 prostate cancer, a Gleason score of 3+4 or less, and a prostate-specific antigen (PSA) level of no more than 20 ng per milliliter were randomly assigned (in a 1:1 ratio) to receive SBRT (36.25 Gy in 5 fractions over a period of 1 or 2 weeks) or control radiotherapy (78 Gy in 39 fractions over a period of 7.5 weeks or 62 Gy in 20 fractions over a period of 4 weeks). Androgen-deprivation therapy was not permitted. The primary end point was freedom from biochemical or clinical failure, with a critical hazard ratio for noninferiority of 1.45. The analysis was performed in the intention-to-treat population.
RESULTS
A total of 874 patients underwent randomization at 38 centers (433 patients in the SBRT group and 441 in the control radiotherapy group) between August 2012 and January 2018. The median age of the patients was 69.8 years, and the median PSA level was 8.0 ng per milliliter; the National Comprehensive Cancer Network risk category was low for 8.4% of the patients and intermediate for 91.6%. At a median follow-up of 74.0 months, the 5-year incidence of freedom from biochemical or clinical failure was 95.8% (95% confidence interval [CI], 93.3 to 97.4) in the SBRT group and 94.6% (95% CI, 91.9 to 96.4) in the control radiotherapy group (unadjusted hazard ratio for biochemical or clinical failure, 0.73; 90% CI, 0.48 to 1.12; P = 0.004 for noninferiority), which indicated the noninferiority of SBRT. At 5 years, the cumulative incidence of late Radiation Therapy Oncology Group (RTOG) grade 2 or higher genitourinary toxic effects was 26.9% (95% CI, 22.8 to 31.5) with SBRT and 18.3% (95% CI, 14.8 to 22.5) with control radiotherapy (P<0.001), and the cumulative incidence of late RTOG grade 2 or higher gastrointestinal toxic effects was 10.7% (95% CI, 8.1 to 14.2) and 10.2% (95% CI, 7.7 to 13.5), respectively (P = 0.94).
CONCLUSIONS
Five-fraction SBRT was noninferior to control radiotherapy with respect to biochemical or clinical failure and may be an efficacious treatment option for patients with low-to-intermediate-risk localized prostate cancer as defined in this trial. (Funded by Accuray and others; PACE-B ClinicalTrials.gov number, NCT01584258.)
Additional Info
Disclosure statements are available on the authors' profiles:
Phase 3 Trial of Stereotactic Body Radiotherapy in Localized Prostate Cancer
N. Engl. J. Med 2024 Oct 17;391(15)1413-1425, N van As, C Griffin, A Tree, J Patel, P Ostler, H van der Voet, A Loblaw, W Chu, D Ford, S Tolan, S Jain, P Camilleri, K Kancherla, J Frew, A Chan, O Naismith, J Armstrong, J Staffurth, A Martin, I Dayes, P Wells, D Price, E Williamson, J Pugh, G Manning, S Brown, S Burnett, E HallFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
External radiotherapy with image-guided intensity-modulated radiation therapy (IMRT) is a standard treatment for localized prostate cancer. The main argument against conventional IMRT is its lengthy treatment course, which poses a burden on healthcare systems. In contrast, stereotactic body radiotherapy (SBRT) treatment is completed in less than 2 weeks, which may be particularly attractive for centers managing high patient volumes. This shorter duration could also benefit patients by reducing out-of-pocket expenses and minimizing the psychological impact associated with daily hospital visits over an extended period.
Prof van As and colleagues recently published the primary analysis of PACE-B, an investigator-initiated multicenter randomized trial in men with localized prostate cancer comparing SBRT with conventionally or moderately fractionated IMRT without any androgen deprivation therapy (ADT). The trial achieved its primary endpoint, demonstrating that the efficacy of SBRT is noninferior to that of standard fractionated IMRT, with 5-year freedom from biochemical or clinical failure rates of 95.8% and 94.6%, respectively. Interestingly, the outcomes in both arms surpassed the initial assumption of 85% biochemical control at 5 years, raising the benchmark for future prostate cancer trials.
Although both approaches yielded good outcomes, the cumulative incidence of late grade 2 or higher genitourinary (GU) toxicity over 5 years was 9% to 12% higher with SBRT than with standard fractionation. It is important to note that a grade 2 urinary event is defined as the need for oral medication, increased frequency, and occasional blood in urine, none requiring any major intervention. The urinary flare-ups seen with SBRT appear to be transient, with no significant difference in grade 2 or higher events at 5 years (8.7% with SBRT vs 6.7% with IMRT; P = .32). Grade 3 GU events were observed in only 1.7% of patients treated with SBRT. Patient-reported outcomes using the EPIC questionnaire did not show significant differences despite variation in physician-reported GU toxicity. Additionally, late gastrointestinal and sexual adverse effects were comparable between the groups, with low rates of erectile dysfunction in both arms likely attributable to the omission of ADT.
This study does not capture patients' perceptions and preferences on treatment duration, which are central to this discussion. However, the PACE-B results will certainly help guide patients in making informed decisions between two equally effective treatment schedules. Approximately 25% of included patients were eligible for active surveillance. This, in itself, may not be a drawback but a strength of the trial. Despite eligibility for active surveillance, this strategy may not always find favor with patients, clinicians, and healthcare systems globally. PACE-B informs about the expected outcomes in such patients when treated with curative radiotherapy. On the other end of the spectrum, the exclusion of patients with high-risk and node-positive prostate cancer from PACE-B limits its applicability to this group. Ongoing PACE-C and PRIME trials are evaluating the efficacy of SBRT in these patients.1,2
Physicians and patients with varied experiences and perspectives may interpret PACE-B results differently, influenced by individual biases and logistical and financial considerations. For instance, some clinicians may view the additional 12% use of medications as an acceptable trade-off and incentivize SBRT to accommodate more patients, while others may prefer a longer treatment schedule. Nevertheless, the overall excellent tumor control achieved in both treatment arms, using a single noninvasive modality without ADT and its associated adverse effects, stands as a testament to advancements in modern radiotherapy.
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