Efficacy and Safety of Ultrahypofractionated Proton Therapy in the Treatment of Prostate Cancer in Real-World Czech Practice
A team from the Prague Proton Therapy Center, led by Associate Professor Jiří Kubeš, published a study with nearly 300 patients in the prestigious International Journal of Radiation Oncology, Biology, Physics. It demonstrates the significant efficacy and low toxicity of the ultrahypofractionated proton therapy regimen in patients with prostate cancer. We summarize the main results.
Ultrahypofractionated Therapy Regimens
Proton radiotherapy as a method for treating prostate cancer offers substantial benefits. Compared to intensity-modulated radiotherapy (IMRT), it shows lower urogenital toxicity and a lower incidence of erectile dysfunction, though it has higher gastrointestinal toxicity. Most available clinical studies, however, describe the results of normofractionated radiotherapy or therapy using passive scattering beam techniques (PS − passive scattering).
With the gradual development of proton radiotherapy, hypofractionated and subsequently ultrahypofractionated regimens have become a reality, reducing the overall radiation dose from the original 35 fractions to as few as 5 fractions (3 or 5 per week). This not only increased compliance with therapy and comfort for patients but also reduced healthcare costs and improved the “throughput” of radiotherapy centers. In the last decade, the original PS method has started to be replaced by more efficient “pencil” scanning (PBS − pencil beam scanning). A detailed analysis of both methods is beyond the scope of this communication; briefly, PBS is a technologically newer method that improves radiation dose distribution, enabling the development of the ultrahypofractionated regimen.
The team from the Proton Therapy Center published unique results from a study of the ultrahypofractionated regimen with PBS technology in a high-impact-factor journal. The study received a ranking value of 6, the highest rating in the field of radiation oncology journals.
Methodology and Study Course
A total of 279 patients who underwent proton radiotherapy at the Proton Therapy Center for low and intermediate-risk prostate cancer between January 2013 and March 2016 were included in the final analysis.
Low and intermediate-risk prostate cancer was verified by biopsy examination. Additional criteria included a prostate-specific antigen (PSA) level of < 15 μg/l (to reduce the risk of subclinical metastatic disease) and a planned target volume not exceeding 150 cm3 (patients with a higher volume were treated with a mildly accelerated regimen of 21 fractions). Neoadjuvant hormone therapy was indicated only in patients with intermediate-risk prostate cancer, based on the decision of the referring urologist or attending radiation oncologist.
Patients were irradiated with a total dose of 36.25 GyE (biological equivalent of photon radiation) in 5 fractions (7.35 GyE per fraction), with a frequency of 1 fraction every other day. Radiation was applied from 2 opposed lateral-lateral fields in the supine position.
Subsequent follow-up was based on monitoring PSA levels at intervals of 3–6 months.
Results
The median follow-up period was 56.5 months (range 3.4–87.5), with 252 (90.3%) patients followed for more than 48 months. Low-risk prostate cancer was identified in 121 (43.4%) patients and intermediate-risk prostate cancer in 158 (56.6%) patients. All underwent full-dose therapy of 36.25 GyE in 5 fractions. The average treatment time was 10 days, with a median treatment time of 9 days (7–18). Forty-nine (17.6%) patients underwent neoadjuvant hormone therapy, and none underwent adjuvant hormone therapy.
Biochemical disease-free survival (bDFS) at 5 years was observed in 96.9% of patients with low-risk prostate cancer (95% confidence interval [CI] 93.3–100.0), 91.7% with favorable intermediate-risk (95% CI 86.0–97.7), and 83.5% with unfavorable intermediate-risk (95% CI 71.1–98.1). Biochemical recurrence occurred in 17 patients (6.1%; 4 in the low-risk group and 13 in the intermediate-risk group). Recurrence was detected in 13 of them, most frequently in lymph nodes. During the follow-up period, a total of 9 patients died, none in direct connection with prostate cancer.
Toxicity analysis focused on late, or chronic toxicity, which is a significant problem with any radiotherapy. Adverse events were assessed according to CTCAE version 4.0 criteria. Gastrointestinal (GI) toxicity grade 2 was observed in 20 (7.2%) patients, and grade 3 GI toxicity in 1 (0.4%). All cases were transient; grade 2 issues were managed with local anti-inflammatory therapy (corticosteroids or mesalazine), and the grade 3 patient experienced bleeding requiring a blood transfusion. Grade 2+ genitourinary toxicity occurred in 14 (5%) patients, with most experiencing new weak urinary stream or urgent incontinence medication.
Conclusion
The results of the Czech study evaluating mid-term outcomes of the ultrahypofractionated regimen using PBS in patients with low and intermediate-risk prostate cancer revealed that this is a highly effective and safe therapeutic modality with many benefits for both the patient and the healthcare system.
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Source: Kubeš J., Haas A., Vondráček V. et al. Ultrahypofractionated proton radiation therapy in the treatment of low and intermediate-risk prostate cancer-5-year outcomes. Int J Radiat Oncol Biol Phys 2021; 110 (4): 1090–1097, doi: 10.1016/j.ijrobp.2021.02.014.
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