Hypofractionated radiation therapy improves 10-year prostate cancer outcomes

CJ Hassanzadeh, MD, MPH

Credit: MD Anderson Cancer Center

Escalated-dose hypofractionated radiation therapy may provide better efficacy versus conventionally fractionated radiation for longer than a decade in patients with localized prostate cancer, according to a longterm analysis of a previously published phase 3 trial.

New data presented at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting in Washington, DC, this weekend showed an escalated dose of hypofractionated radiation was associated with a 47% improved 10-year failure rate compared to fractionated radiation therapy in men with localized prostate cancer. The findings also showed no significant differences in longterm toxicity between the treatment options, as well as similar overall survival rates.

Led by CJ Hassanzadeh, MD, MPH, assistant professor of radiation oncology at The University of Texas MD Anderson Cancer Center and clinical director of the Bone Metastasis Clinic, investigators aimed to build on prior prospective phase 3 study findings showing “superior (prostate) cancer control” with hypofractionated radiation. Their longterm outcome analysis sought to determine whether the initial superiority was maintained between the two.

Indeed, prior research comparing hypofractionated versus conventional radiation therapy has shown at least a consistent tolerability or safety profile between the dosage options in patients with genitourinary cancers, complementary to the efficacy findings in initial research into prostate cancer.

In this analysis, Hassanzadeh and colleagues randomized men with localized prostate cancer to either conventional fractionated or hypofractionated radiation therapy between 2001 – 2010. The conventional dose entailed 75.6Gy delivered in 1.8-Gy fractions over 8.4 weeks; the hypofractionated dose was 72Gy delivered in 2.4-Gy fractions over 6 weeks. All patients’ radiotherapy doses were modulated for intensity.

The patient arms were stratified at treatment randomization based on receipt of androgen deprivation therapy (ADT) and prostate-specific antigen (PSA) levels ≤10 ng/mL to ensure balanced patient characteristics. The team used modified Radiation Therapy Oncology Group (RTOG) criteria to grade late gastrointestinal and genitourinary toxicity.

Investigators sought a primary outcome of failure per PSA nadir plus 2 ng/mL, or initiation of salvage therapy. They calculated time to failure by start of radiation; time to toxicity was measured from the end of radiation.

The team enrolled 206 patients with localized prostate cancer; a majority had intermediate National Comprehensive Cancer Network (NCCN) grades (71%) and PSA ≤10 ng/mL (90% at baseline. Approximately half (48%) had Gleason grade group 2 cancer. Participants were split 1:1 to either conventional (n = 102) or hypofractionated (n = 104) radiation regimens.

Patients were followed up for a median of 11 years; one-fourth (24%) were administered ADT in that time.

Only 13 patients receiving hypofractionated radiation therapy experienced treatment failure, versus 22 patients receiving a conventional regimen—however, the outcome was not statistically significant (P = .077). Patients receiving hypofractionated regimen reported an 11% failure rate over 10 years (95% CI, 5.5 – 18.1), versus 21% among the conventional regimen (95% CI, 13.0 – 30.5).

Investigators observed a significantly improved 10-year failure rate among the subgroup of men receiving hypofractionated radiation therapy who did not receive ADT (13%), versus the subgroup of men receiving conventional radiation therapy who did not receive ADT (26%; P = .039).

That said, median overall survival over 20 years was similar across the 2 treatment arms (P = .076), as well as the 15-year distant metastasis rate (8% vs 4%; P = .22).

Regarding safety, Hassanzadeh and colleagues noted similar 10-year, cumulative grade ≥2 genitourinary toxicity between the hypofractionated arm (26%) and conventional arm (23%; P = .54), as well as rates of grade ≥2 gastrointestinal toxicity (13% vs 5%, respectively; P = .08). The team reported no grade 4 toxicities among the treated patients.

“Long-term outcomes suggest a benefit in terms of treatment failure to dose-escalated, hypofractionated radiation, especially among patients not receiving ADT, without worse late toxicity,” the investigators concluded.

References

1. ^{Hassanzadeh, CJ, Kuban DA, Pasya S, Bassett R, et al. Hypofractionated, Dose-Escalated Radiation vs. Conventionally Fractionated Radiation for Localized Prostate Cancer: Long-Term Update of a Phase 3, Prospective, Randomized Controlled Trial. Poster presented at: American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting. Washington, DC. September 29 – October 2, 2024.}
2. ^{Saylor B. Hypofractionated prostate RT does not increase toxicity vs conventional RT. Urology Times. Published October 29, 2021. Accessed September 27, 2024. https://www.urologytimes.com/view/hypofractionated-prostate-rt-does-not-increase-toxicity-vs-conventional-rt}