A shortened course of radiation therapy is safe and effective for men with high-risk prostate cancer, according to the results of the phase 3 Prostate Cancer Study 5 (PCS5) trial. These findings were presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting 2022 by the study’s lead investigator Tamim M. Niazi, MD, Associate Professor, Radiation Oncology, and Radiation Oncologist, Jewish General Hospital, McGill University, Montréal, Québec, Canada.
“This is the first phase 3 study of moderate hypofractionated radiotherapy in high-risk prostate cancer patients treated with contemporary radiation fields and long-term ADT [androgen deprivation therapy]. The survival curves were identical. Hypofractionated radiotherapy is as effective as conventional radiotherapy with similar, acceptable toxicity, and we think this should be the new standard of care,” Dr Niazi said during his presentation. Moderately shortened (hypofractionated) radiotherapy has been confirmed as an effective strategy for low-, intermediate-, and mixed-risk prostate cancer. The results of the PCS5 trial extend this to include high-risk prostate cancer.
Given similar safety and efficacy, 5 weeks of radiation has a number of advantages for the patient and the healthcare system, Dr Niazi said. “Hypofractionated treatment for prostate cancer decreases the financial toxicity to patients, and it is completed in 25 days instead of the usual 38 to 40 days. That’s 3 weeks of not having to come to the clinic—the transportation, parking costs, and just the time it takes away from a person’s day-to-day life,” he explained.
The PCS5 trial enrolled 329 men at 12 different sites in Canada from February 2012 to March 2015 and randomized them in a 1:1 ratio to receive moderately hypofractionated radiotherapy (48 Gy in 25 daily sessions; N = 159) or conventional radiotherapy (76 Gy in 38 daily sessions; N = 160). Enrollment criteria stipulated high-risk disease (Gleason score of 8 to 10, stage T3a or higher, or a prostate-specific antigen level >20). Patients received radiation to the pelvic lymph nodes and long-term ADT (28 months) before, during, and after radiation (median duration, 24 months).
Baseline demographics were well balanced across the 2 arms. The majority of patients had Gleason scores of 8 to 10. More than 60% received intensity-modulated radiotherapy.
At 7 years of follow-up, overall survival among evaluable patients was almost identical for the hypofractionated arm versus the standard radiotherapy arm (81.7% vs 82%, respectively). Prostate cancer–specific mortality was also almost identical (94.9% vs 96.4%, respectively). Biochemical failure–free survival was 87.4% versus 85.1%, respectively, and distant metastatic recurrence–free survival was 91.5% versus 91.8%, respectively. Disease-free survival (including biochemical recurrence or distant recurrence) was also similar (86.5% vs 83.4%, respectively).
No differences in survival, prostate cancer–free survival, biochemical failure, and rates of distant metastases were found between the 2 study arms at 3, 5, and 7 years, which Dr Niazi said indicated equivalency at these time points.
“Acute toxicity was pretty similar between the two arms,” Dr Niazi said. There were no significant differences in grade ≥3 acute and delayed genitourinary and gastrointestinal toxicities at 2 years, and no new toxicities were reported after that. Minimal grade 3 toxicity was observed in either study arm. No grade 4 toxicities were reported in either arm.
At 6 months from randomization, the rate of grade 2 toxicities was 55% in the hypofractionated radiotherapy arm versus 49% in the conventional radiotherapy arm.
At a press conference where the results were presented, ASTRO President-Elect Jeff Michalski, MD, MBA, FASTRO, Carlos A. Perez Distinguished Professor and Vice-Chairman, Department of Radiation Oncology, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, said this was an important trial.
“Adoption of shorter courses of radiation has been very slow and it is not yet considered a standard of care for high-risk prostate cancer. That’s why this trial is so important. This trial has shown that reducing the number of treatments that included lymph node irradiation was tolerable with no increased toxicity,” Dr Michalski said.
“I do think that this study will lead to seeing shorter courses of radiation available to our oncology community for high-risk prostate cancer patients. Thank you for this practice-changing trial,” he said, commending the investigators.