Hypofractionated radiotherapy is emerging as a promising treatment approach for prostate cancer, offering potential benefits in both post-prostatectomy and primary localized disease settings. Recent studies presented at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting and discussed in other venues highlight the efficacy and safety of this approach, which involves delivering higher doses of radiation over fewer sessions compared to conventional fractionation.
HYPORT-ES Trial: Hypofractionation in Post-Prostatectomy Patients
The HYPORT-ES trial, a Phase II study, evaluated hypofractionated postoperative radiotherapy in prostate cancer. The trial's design involved administering 62.5 Gy in 25 fractions for adjuvant and salvage radiotherapy. The study, which included 405 patients from 23 Spanish centers, reported low rates of acute and late gastrointestinal and genitourinary toxicity. At three years, the biochemical control rate was an impressive 93%.
Dr. Asunción Hervás, Head of Brachytherapy and GU Tumor Unit at Ramón y Cajal Hospital, Madrid, Spain, presented these results, noting that the toxicity rates were potentially lower than those observed with conventional fractionation. "Moderate hypofractionation is a promising approach with similar or lower toxicity levels with the same efficacy in the salvage and adjuvant radiotherapy. And definitely, the new technology is the key to these good results. Now we can design very precise and safe treatments," Dr. Hervás stated.
The primary endpoints of the trial focused on the incidence of treatment-related acute and late gastrointestinal and genitourinary adverse events. Secondary endpoints included biochemical failure-free survival, disease-free survival, overall survival, and quality of life. The results indicated that Grade 2 or higher acute genitourinary toxicity was observed in only 7% of patients, with 1% experiencing Grade 3 toxicity. Gastrointestinal toxicity was even lower, with no Grade 3 events reported. Chronic toxicities were slightly higher but remained relatively low, with approximately 10% Grade 2 and 2% Grade 3 genitourinary toxicity, and around 1% Grade 2 and Grade 3 gastrointestinal toxicity.
Long-Term Outcomes of Dose-Escalated Hypofractionation for Localized Prostate Cancer
Another study presented at the ASTRO 2024 Annual Meeting by Dr. Comron Hassanzadeh from The University of Texas MD Anderson Cancer Center, provided long-term results of a phase III randomized trial comparing hypofractionated, dose-escalated radiotherapy (HIMRT) to conventionally fractionated radiotherapy (CIMRT) for clinically localized prostate cancer. The study aimed to determine whether dose-escalated HIMRT was associated with superior cancer control outcomes compared to CIMRT.
The trial randomized patients with localized prostate cancer to either CIMRT (75.6 Gy in 1.8-Gy fractions over 8.4 weeks) or dose-escalated HIMRT (72 Gy in 2.4-Gy fractions over 6 weeks). The primary endpoint was biochemical failure, defined as PSA nadir + 2 (Phoenix criteria) or the need for salvage therapy. After a median follow-up of 11 years, the 10-year failure rate was 11% in the HIMRT group compared to 21% in the CIMRT group (p=0.077). Although this difference was not statistically significant, a subgroup analysis of patients who did not receive androgen deprivation therapy (ADT) showed a significant improvement in the 10-year failure rate with HIMRT (13%) compared to CIMRT (26%; p=0.039).
Regarding toxicity, the 10-year rate of GI grade ≥2 events was higher in the HIMRT group (13% versus 5%, p=0.08), but there were no significant differences in GU grade ≥2 toxicity. Overall survival was similar between the two groups.
Implications for Clinical Practice
The growing body of evidence supporting hypofractionated radiotherapy suggests that it could become a standard of care for both post-prostatectomy and primary treatment of localized prostate cancer. The convenience of fewer treatment sessions, combined with comparable or lower toxicity rates and promising oncologic outcomes, makes it an attractive option for many patients.
Dr. Hervás recommends the use of moderate hypofractionation, emphasizing that "it's more convenient for the institution and for the patients, and it's safe... the patients are very happy with reducing the number of sessions." She also notes the importance of advanced radiotherapy techniques and individual patient factors in treatment decisions.
While longer-term data is still needed to confirm chronic toxicity and efficacy outcomes, the current evidence suggests that hypofractionated radiotherapy is a valuable tool in the fight against prostate cancer.
