In a presentation at the 2023 LUGPA Annual Meeting, Dr. Daniel Spratt outlined the evolution of radiotherapy in prostate cancer and highlighted ongoing research into new techniques designed to be less invasive, more precise and safer for this population patients.1
Improved toxicity, improved technology and new techniques have helped increase the use of radiation therapy to treat different subsets of prostate cancer patients, according to Spratt.
“Radiation therapy continues to expand its role, especially if you start talking about [patients with] ultra high risk [prostate cancer] or positive node [disease] and beyond,” Spratt said in a presentation on Updates in Radiation Oncology. Spratt is Vincent K. Smith, chairman of the division of radiation oncology and senior physician at University Hospitals Seidman Cancer Center, as well as professor and chairman of the division of radiation oncology at Case Comprehensive Cancer Center in Cleveland, Ohio.
Spratt began by highlighting how advances in technology have helped reduce the adverse effects (AEs) associated with radiation therapy in prostate cancer patients. The use of 2D radiation from the 1950s to the 1980s was associated with a rectal bleeding rate of 32%, and treatment took 71 days to complete.
The introduction of 3D radiotherapy improved these adverse events, with 8% of patients reporting bothersome rectal toxicity, and intensity-modulated radiotherapy was associated with grade 3 or higher rectal toxicity in approximately 1% to 3% of patients.
However, the introduction of a spacer gel allowed another significant reduction in toxicity. “On top of the marker are multiple spacer gels that can be used to separate the prostate from the rectum. It is currently estimated that over half of all patients receiving radiation therapy for prostate cancer in the United States have a spacer,” Spratt said.
In terms of current trials, Spratt pointed to findings from the phase 3 HYPO-RT-PC trial (ISRCTN45905321) showing that ultra-hypofractionated radiotherapy was non-inferior to conventionally fractionated radiotherapy in terms of failure-free survival in patients with intermediate or high risk of prostate cancer (adjusted HR, 1.002; 95% CI, 0.758-1.325; log-rank P = 0.99). Additionally, early adverse events were more pronounced with ultrahypofractionation versus conventional fractionation, although late toxicity was comparable between groups.2
He also outlined the 5-year findings from the phase 3 PACE-B trial (NCT01584258), which were presented at the 2023 ASTRO Annual Meeting, where the study authors concluded that stereotactic body radiotherapy (SBRT) should is considered a new standard of care for patients with low and favorable intermediate risk prostate cancer, as patients treated with SBRT had a 5-year event-free survival of 95.8% (95% CI, 93.3% -97.3%) vs 94.6% (95% CI, 91.9%- 96.4%) for those treated with conventional fractionated radiotherapy (HR, 0.73; 95% CI, 0.47-1 ,12; log-rank P = .22).3
“Radiation has changed a lot. Patients are familiar with SBRT,” Spratt said. “They’re hearing it because in many cancers, especially metastases, SBRT is playing an increasingly important role. Treatment has changed a lot.”
Over time, shorter regimens have been integrated into the care of prostate cancer patients. Spratt noted that 5 clinical trials are currently underway investigating 2 radiotherapy treatments in selected prostate cancer patients. He explained that after prostatectomy he currently only uses 20 treatments, and trials have also looked at using only 5 radiotherapy treatments for these patients.
Another approach currently being explored in prostate cancer is a concept called dose painting, where instead of receiving a constant dose of radiation to the entire prostate, patients receive a very high dose to the dominant node and a reduced dose to the entire prostate gland. “Do we really need to give this entire dose to the entire prostate? Can we give a microscopic dose so that we are very unlikely to cause so many urinary problems and lower grade rectal AEs? Those trials are also ongoing,” Spratt explained.
Finally, Spratt delved into the findings of a study that used an artificial intelligence (AI) predictive model to identify intermediate-risk prostate cancer patients most likely to benefit from the addition of androgen deprivation therapy (ADT) to radiation versus those who may need only radiation alone.4
In patients selected from 5 phase 3 clinical trials who were positive for an AI pattern and expected to benefit from the addition of ADT, radiotherapy plus ADT was associated with an improvement in distant metastasis-free survival (DMFS) versus radiotherapy alone (HR, 0.34; 95% CI, 0.19–0.63; P < 0.001). In contrast, in patients who were negative for the AI pattern, the addition of ADT to radiotherapy was not associated with an improvement in DMFS (HR, 0.92; 95% CI, 0.59–1.43; P = 0.71).
“[With the use of] biomarkers, I think men would be happy if they could safely avoid hormone therapy,” Spratt concluded.
1. Spratt D. What’s new in radiation oncology. Presented at: LUGPA Annual Meeting 2023; November 2-4, 2023; Orlando, Florida.
2. Widmark A, Gunnlaugsson A, Beckman L, et al. Ultrahypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year results of the randomized, non-inferiority phase 3 trial of HYPO-RT-PC. 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 results of PACE-B: an international phase III randomized controlled trial comparing stereotactic body radiotherapy (SBRT) versus conventionally fractionated or moderately hypofractionated external beam radiotherapy for localized prostate cancer. Presented at: ASTRO 2023 Annual Meeting; October 1-4, 2023; San Diego, California. Summary LBA 03.
4. Spratt DE, Tang S, Sun Y, et al. An artificial intelligence predictive model for hormone therapy use in prostate cancer. NEJM Evid. 2023; 2 (8). doi:10.1056/EVIDoa2300023