Stereotactic Body Radiotherapy for Localized Prostate Cancer

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.

References

1. PACE - The Institute of Cancer Research, London. International randomised study of prostatectomy vs stereotactic body radiotherapy (SBRT) and conventional radiotherapy vs SBRT for organ-confined prostate cancer. Accessed 2024 Nov 13. Available at: https://www.icr.ac.uk/our-research/
2. Murthy V, Mallick I, Gavarraju A, et al. Study protocol of a randomised controlled trial of prostate radiotherapy in high-risk and node-positive disease comparing moderate and extreme hypofractionation (PRIME TRIAL). BMJ Open. 2020;10(2):e034623. https://bmjopen.bmj.com/