Role of Radiation Continues to Grow in the Treatment of Prostate Cancer

Improved toxicity, advanced technology, and novel techniques have helped increase the use of radiotherapy for the treatment of different subgroups of patients with prostate cancer, according to Daniel Spratt, MD.

“Radiation therapy continues to expand its role, especially if you start talking about [patients with] the ultra high–risk [prostate cancer] or node-positive [disease] and beyond,” Spratt said in a presentation on updated in radiation oncology during the 2023 LUGPA Annual Meeting.¹

During his presentation, Spratt outlined the evolution of radiotherapy in prostate cancer and highlighted ongoing research of novel techniques designed to be less invasive, more accurate, and safer for this patient population. Spratt is the Vincent K. Smith Chair of the Department of Radiation Oncology and a senior physician at University Hospitals Seidman Cancer Center, and a professor and chair of the Department of Radiation Oncology at Case Comprehensive Cancer Center in Cleveland, Ohio.

Spratt opened by highlighting how advances in technology have helped reduce adverse effects (AEs) associated with radiotherapy for patients with prostate cancer. The use of 2D radiation from the 1950s into the 1980s was linked with a rectal bleeding rate of 32%, and the treatment took 71 days to complete.

The introduction of 3D radiotherapy improved these AEs, with 8% of patients reporting bothersome rectal toxicity, and intensity-modulated radiation therapy was associated with grade 3 or higher rectal toxicity in approximately 1% to 3% of patients.

However, the introduction of spacer gel has enabled another significant reduction of toxicity. “There are multiple spacer gels on the marker that can be used to separate the prostate from the rectum. Right now, it's estimated over half of all patients that get radiation therapy for prostate cancer in the United States have a spacer,” Spratt said.

Regarding modern trials, Spratt pointed to findings from the phase 3 HYPO-RT-PC trial (ISRCTN45905321), which showed that ultra-hypofractionated radiotherapy was non-inferior vs conventionally fractionated radiotherapy regarding failure-free survival in patients with intermediate- or high-risk prostate cancer (adjusted HR, 1.002; 95% CI, 0.758-1.325; log-rank P = .99). Additionally, early AEs were more pronounced with ultra-hypofractionation vs conventional fractionation, although late toxicity was comparable between the groups.²

He also outlined 5-year findings from the phase 3 PACE-B trial (NCT01584258) that were presented at the 2023 ASTRO Annual Meeting, where study authors concluded that stereotactic body radiation therapy (SBRT) should be considered a new standard of care for patients with low- and favorable intermediate–risk prostate cancer after patients treated with SBRT experienced a 5-year event-free survival rate of 95.8% (95% CI, 93.3%-97.3%) vs 94.6% (95% CI, 91.9%-96.4%) for those treated with conventionally fractionated radiotherapy (HR, 0.73; 95% CI, 0.47-1.12; log-rank P = .22).³

"Radiation has changed a ton. Patients are familiar with SBRT,” Spratt said. “They're hearing it because in many cancers, especially in the metastatic setting, SBRT is playing more and more of a role. Treatment has changed quite a bit.”

Over time, shorter regimens have been integrated into the care for patients with prostate cancer. Spratt noted that 5 clinical trials are currently underway examining 2 treatments with radiotherapy in select patients with prostate cancer. He explained that following prostatectomy, he currently uses only 20 treatments, and trials have also looked at using just 5 radiation treatments for these patients.

Another approach currently under investigation in the prostate cancer space is a concept called “dose painting,” where rather than getting a consistent dose of radiation to the whole prostate, patients receive a very high dose to the dominant nodule and a reduced dose to the whole gland. “Do we really need to give all of that dose to the whole prostate? Can we give a microscopic dose so we're very unlikely to cause as much a urinary bother and lower-grade rectal AEs? These trials are ongoing as well,” Spratt explained.

Finally, Spratt delved into findings from a study using an artificial intelligence (AI) predictive model to identify patients with intermediate-risk prostate cancer who would most likely benefit for the addition of androgen deprivation therapy (ADT) to radiation vs those who may only need radiation alone.⁴

In patients drawn from 5 phase 3 clinical trials who were AI model positive and expected to derive benefit from the addition of ADT, radiotherapy plus ADT was associated with an improvement in distant metastasis–free survival (DMFS) vs radiotherapy alone (HR, 0.34; 95% CI, 0.19–0.63; P < .001). Conversely, in patients who were AI model negative, the addition of ADT to radiotherapy was not associated with an improvement in DMFS (HR, 0.92; 95% CI, 0.59–1.43; P = .71).

"[With the use of] biomarkers, I think men will love if they can safely avoid hormone therapy," Spratt concluded.

References

1. Spratt D. What’s new in radiation oncology. Presented at: 2023 LUGPA Annual Meeting; November 2-4, 2023; Orlando, FL.
2. Widmark A, Gunnlaugsson A, Beckman L, et al. Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet. 2019;394(10196):385-395. doi:10.1016/S0140-6736(19)31131-6
3. van As N, Tree A, Patel J, et al. 5-year outcomes from PACE-B: An international phase III randomized controlled trial comparing stereotactic body radiotherapy (SBRT) vs conventionally fractionated or moderately hypofractionated external beam radiotherapy for localised prostate cancer. Presented at: 2023 ASTRO Annual Meeting; October 1-4, 2023; San Diego, CA. Abstract LBA 03.
4. Spratt DE, Tang S, Sun Y, et al. Artificial intelligence predictive model for hormone therapy use in prostate cancer. NEJM Evid. 2023;2(8). doi:10.1056/EVIDoa2300023