Radiotherapy for Prostate Cancer: What Approach Works Best?

TOPLINE:

Moderately hypofractionated radiotherapy, both isodose and dose-escalated, led to progression-free survival outcomes similar to that achieved with conventionally fractionated radiotherapy in patients with prostate cancer, but the dose-escalated regimen came with an increased risk for toxicities compared with the conventional approach, according to findings from a recent meta-analysis.

METHODOLOGY:

• Moderately hypofractionated radiotherapy is now the preferred standard for treating localized prostate cancer, but the optimal regimen remains uncertain.
• Researchers conducted a meta-analysis of seven phase 3 trials, which included 5880 patients with prostate cancer who received either conventionally fractionated radiotherapy or moderately hypofractionated radiotherapy.
• Three trials (n = 3454) compared conventionally fractionated radiotherapy with isodose moderately hypofractionated radiotherapy, and four trials (n = 2426) compared the conventional approach with dose-escalated hypofractionated approach. The median follow-up durations were 5.4 and 7.1 years, respectively.
• The meta-analysis included three separate assessments: Efficacy, physician-scored late toxicity, and patient-reported outcomes. The primary endpoint for efficacy was progression-free survival; overall survival was the secondary endpoint. The late toxicity analysis evaluated the incidence of late grade ≥ 2 genitourinary and gastrointestinal toxic effects as co-primary endpoints, with late grade ≥ 3 toxicity as secondary endpoints. The patient-reported outcomes were clinically important declines in urinary or bowel scores.

TAKEAWAY:

• Progression-free survival was not significantly different between patients who received isodose or dose-escalated moderately hypofractionated radiotherapy vs conventionally fractionated radiotherapy (hazard ratio [HR], 0.92 for isodose; P = .21; HR, 0.94 for dose-escalated; P = .43).
• Overall survival was also similar when comparing the hypofractionated treatments to the conventional approach (HR, 0.83 for isodose; P = .06, and HR, 0.92; P = .39 for dose-escalated).
• Compared with the conventional approach, isodose moderately hypofractionated radiotherapy was not associated with a greater likelihood of late grade ≥ 2 (odds ratio [OR], 1.16; P = .32) or grade ≥ 3 genitourinary toxicities (OR, 1.15; P = .27) as well as grade ≥ 2 (OR, 1.20; P = .51) or grade ≥ 3 (OR, 0.89; P = .76) gastrointestinal toxicities.
• Dose-escalated moderately hypofractionated radiotherapy, however, was associated with significantly higher odds of experiencing late grade ≥ 2 (OR, 1.48) and late grade ≥ 3 (OR, 1.80) gastrointestinal toxicities. Patients who received the dose-escalated regimen were also more likely to experience a decrease in bowel quality of life (OR, 1.68).

IN PRACTICE:

This meta-analysis provides the strongest evidence to date suggesting an isodose regimen could be the preferred hypofractionated regimen for all risk groups, the authors concluded.

However, whether the authors’ conclusions concerning dose-escalated moderately hypofractionated radiotherapy “hold true in an era of focal boosting and [stereotactic body radiotherapy] is a matter of constructive debate,” authors of an accompanying editorial wrote.

SOURCE:

This study, led by Amar U. Kishan, MD, Department of Radiation Oncology, University of California Los Angeles, and Yilun Sun, PhD, Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Cleveland, was published online in The Lancet Oncology.

LIMITATIONS:

Differences in trial definitions for progression-free survival and toxicity required data harmonization. Patient-reported outcomes were not available for three trials, limiting the robustness of these analyses. The median follow-up was relatively short, and very late differences in toxicity and efficacy might manifest with extended follow-up. Time-to-toxicity data were not available, and therefore, physician-scored toxic effect data were evaluated as binary events rather than time-based incidences.

DISCLOSURES:

This study did not receive any specific funding. Several authors reported receiving personal fees or grants and having other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.