Multi-institutional retrospective analysis of ultrahypofractionated radiotherapy for Japanese prostate cancer patients

Abstract

To report outcomes and risk factors of ultrahypofractionated (UHF) radiotherapy for Japanese prostate cancer patients. This multi-institutional retrospective analysis comprised 259 patients with localized prostate cancer from 6 hospitals. A total dose of 35–36 Gy in 4–5 fractions was prescribed for sequential or alternate-day administration. Biochemical failure was defined according to the Phoenix ASTRO consensus. Toxicities were assessed using National Cancer Institute Common Toxicity Criteria version 4. Tumor control and toxicity rates were analyzed by competing risk frames. Median follow-up duration was 32 months (range 22–97 months). 2- and 3-year biochemical control rates were 97.7% and 96.4%, respectively. Initial prostate-specific antigen (p < 0.01) and neoadjuvant androgen deprivation therapy (p < 0.05) were identified as risk factors for biochemical recurrence. 2- and 3-year cumulative ≥ Grade 2 late genitourinary (GU) toxicities were 5.8% and 7.4%, respectively. Corresponding rates of gastrointestinal (GI) toxicities were 3.9% and 4.5%, respectively. Grade 3 rates were lower than 1% for both GU and GI toxicities. No grade 4 or higher toxicities were encountered. Biologically effective dose was identified as a risk factor for ≥ Grade 2 late GU and GI toxicities (p < 0.05). UHF radiotherapy offered effective, safe treatment for Japanese prostate cancer with short-term follow-up. Our result suggest higher prescribed doses are related to higher toxicity rates.

Ultrahypofractionated Radiotherapy versus Conventional to Moderate Hypofractionated Radiotherapy for Clinically Localized Prostate Cancer

“… DeRT = dose escalated radiotherapy, UHF = ultrahypofractionated radiotherapy, H-UHF = high-dose UHF (EQD2 > 100 Gy 1.5 ), L-UHF = low-dose UHF (EQD2 ≤ 100 Gy 1.5 ), fr = fractions, EQD2 = n × d ([α/β] + d)/([α/β] + 2) where n = number of treatment fractions, d = dose per fraction in Gy, α/β = 1.5 Gy. Koontz et al reported that EQD2 > 100 Gy 1.5 might cause high rates of >Grade 2 toxicities [ 9 ] and Ishiyama et al confirmed those results [ 4 ]. Therefore, we examined the impact of this threshold not only on toxicity but also on the efficacy of UHF and DeRT, dividing UHF into two subgroups: H-UHF and L-UHF groups, using a cut-off value of EQD2 = 100 Gy 1.5 .…”

“…The detailed method of radiotherapy (UHF [ 4 , 5 ] or DeRT [ 6 ] in Uji-Takeda Hospital [ 8 ]) has been described elsewhere. All patients were treated with UHF or DeRT at various fractions ( Table 2 ).…”

“…All patients were treated with UHF or DeRT at various fractions ( Table 2 ). According to previous studies, we divided the UHF group into two subgroups: H-UHF and L-UHF groups, using a cut-off value of EQD2 = 100 Gy 1.5 (α/β = 1.5 Gy) [ 4 , 9 ].…”

“…Ishiyama et al reported an early experience of the safety and effectiveness of UHF in Japan using multi-institution data accumulation and created an open database for exploration [ 4 , 5 , 6 ]. We aimed to compare the outcomes of UHF with those of conventional to moderate hypofractionated radiotherapy.…”

Comparison of toxicities between ultrahypofractionated radiotherapy versus brachytherapy with or without external beam radiotherapy for clinically localized prostate cancer

“…Although several randomized controlled trials indicated the superiority of BT boost over external beam radiotherapy alone 8 – 10 not only in LDR 8 but also in HDR 9 , 10 , there is a lack of conclusive data comparing BT ± EBRT and UHF 11 – 15 . Therefore, to compare the results of UHF to BT ± EBRT, we used open data constructed by multi-institution data accumulation in Japan 16 . In addition, as previous studies cited that a BED over 226 Gy 1.5 might be a threshold to cause higher rates of grade > 2 toxicities 16 , 17 in UHF, we divided the UHF group into L-UHF (BED < 226 Gy 1.5 ) and H-UHF (BED ≥ 226 Gy 1.5 ) groups using this threshold.…”