Kishan Amar U, Sun Yilun, Tree Alison C, Hall Emma, Dearnaley David, Catton Charles N, Lukka Himanshu R, Pond Gregory, Lee W Robert, Sandler Howard M, Feng Felix Y, Nguyen Paul L, Incrocci Luca, Heemsbergen Wilma, Pos Floris J, Horwitz Eric, Wong Jessica Karen, Hoffman Karen E, Hassanzadeh Comron, Kuban Deborah A, Arcangeli Stefano, Sanguineti Giuseppe, Supiot Stephane, Crehange Gilles, Latorzeff Igor, Kalbasi Tahmineh Romero, Steinberg Michael L, Valle Luca F, Loblaw Andrew, Nikitas John, Roy Soumyajit, Zaorsky Nicholas G, Jia Angela Y, Spratt Daniel E
Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA.
Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Lancet Oncol. 2025 Apr;26(4):459-469. doi: 10.1016/S1470-2045(25)00034-8. Epub 2025 Mar 17.
Trials comparing moderately hypofractionated radiotherapy (MHFRT) to conventionally-fractionated radiotherapy (CFRT) for prostate cancer have varied considerably in intent (non-inferiority vs superiority) and MHFRT dose. We compare the efficacy and toxicity profiles of isodose MHFRT and dose-escalated MHFRT.
This was an individual patient data meta-analysis that identified randomised phase 3 trials of CFRT versus MHFRT that had published individual patient-level data on efficacy and late toxicity. A systematic literature search using MEDLINE, Embase, trial registries, the Web of Science, Scopus, and relevant conference proceedings was initially conducted on Dec 15, 2023, and was re-conducted on Jan 8, 2025. Trials that did not publish efficacy data, did not publish late toxicity data, or did not use modern dose radiotherapy (≥70 Gy in 2 Gy equivalents) in the CFRT group were excluded. Individual patient data were provided to MARCAP by study investigators. Three separate meta-analyses were designed to compare efficacy (primary endpoint was progression-free survival), physician-scored late toxicity (co-primary endpoints were late grade 2 or higher genitourinary and late grade 2 or higher gastrointestinal toxic effects), and patient-reported outcomes (co-primary endpoints were clinically-significant decrements in patient-reported urinary or bowel quality of life) between patients receiving CFRT versus MHFRT.
We identified 1696 records for review. Seven phase 3 trials comparing MHFRT with CFRT were eligible for inclusion in our analysis. Individual patient data were obtained from these seven studies (3454 patients from three trials comparing CFRT with isodose MHFRT and 2426 patients from four trials comparing CFRT with dose-escalated MHFRT). At a median follow-up of 5·4 years (IQR 4·6-7·2) for isodose MHFRT and 7·1 years (5·7-8·4) for dose-escalated MHFRT, no differences in progression-free survival were detected (hazard ratio 0·92, 95% CI 0·81-1·05; p=0·21 and 0·94, 0·82-1·09; p=0·43 respectively). No increased odds of grade 2 or higher genitourinary toxic effects were identified for either isodose (odds ratio [OR] 1·16, 95 CI% 0·86-1·57; p=0·32) or dose-escalated MHFRT (1·20, 0·95-1·51; p=0·13). The odds of grade 2 or higher gastrointestinal toxic effects were significantly higher with dose-escalated (OR 1·48, 95% CI 1·14-1·92; p=0·0035) but not isodose MHFRT (1·30, 0·59-2·87; p=0·51). Isodose MHFRT was not found to show different odds of urinary quality-of-life decrement (OR 1·03, 95% CI 0·51-2·09; p=0·93) or bowel quality-of-life decrement (0·76, 0·40-1·43; p=0·39). Dose-escalated MHFRT was associated with greater odds of bowel quality-of-life decrement (OR 1·68, 95% CI 1·07-2·61; p=0·023), but no evidence of greater urinary quality-of-life decrement was found (1·57, 0·87-2·85; p=0·13).
Isodose MHFRT and dose-escalated MHFRT both have similar efficacy compared with CFRT, but dose-escalated MHFRT is associated with higher physician-scored and patient-reported bowel toxicity. Isodose regimens, eg, 60 Gy in 20 fractions, should be the standard MHFRT regimen for localised prostate cancer.
None.
比较中度低分割放疗（MHFRT）与传统分割放疗（CFRT）治疗前列腺癌的试验在研究目的（非劣效性与优效性）和MHFRT剂量方面差异很大。我们比较了等剂量MHFRT和剂量递增MHFRT的疗效和毒性特征。
这是一项个体患者数据荟萃分析，纳入了比较CFRT与MHFRT的随机3期试验，这些试验已发表了关于疗效和晚期毒性的个体患者水平数据。最初于2023年12月15日使用MEDLINE、Embase、试验注册库、科学网、Scopus和相关会议记录进行了系统文献检索，并于2025年1月8日重新进行。未发表疗效数据、未发表晚期毒性数据或CFRT组未使用现代剂量放疗（≥70 Gy，以2 Gy等效剂量计）的试验被排除。研究调查人员将个体患者数据提供给MARCAP。设计了三项独立的荟萃分析，以比较接受CFRT与MHFRT的患者之间的疗效（主要终点为无进展生存期）、医生评分的晚期毒性（共同主要终点为晚期2级或更高等级的泌尿生殖系统和晚期2级或更高等级的胃肠道毒性反应）以及患者报告的结局（共同主要终点为患者报告的泌尿或肠道生活质量的临床显著下降）。
我们识别出1696条记录以供审查。七项比较MHFRT与CFRT的3期试验符合纳入我们分析的条件。从这七项研究中获得了个体患者数据（三项比较CFRT与等剂量MHFRT的试验中有3454例患者，四项比较CFRT与剂量递增MHFRT的试验中有2426例患者）。等剂量MHFRT的中位随访时间为5.4年（四分位间距4.6 - 7.2），剂量递增MHFRT的中位随访时间为7.1年（5.7 - 8.4），未检测到无进展生存期的差异（风险比0.92，95%置信区间0.81 - 1.05；p = 0.21；以及0.94，0.82 - 1.09；p = 0.43）。等剂量（优势比[OR] 1.16，95%置信区间0.86 - 1.57；p = 0.32）或剂量递增MHFRT（1.20，0.95 - 1.51；p = 0.13）均未发现2级或更高等级泌尿生殖系统毒性反应的几率增加。剂量递增MHFRT导致≥2级胃肠道毒性反应的几率显著更高（OR 1.48，95%置信区间1.14 - 1.92；p = 0.0035），但等剂量MHFRT未出现这种情况（1.30，0.59 - 2.87；p = 0.51）。未发现等剂量MHFRT在导致尿生活质量下降（OR 1.03，95%置信区间0.51 - 2.09；p = 0.93）或肠道生活质量下降（0.76，0.40 - 1.43；p = 0.39）方面有不同的几率。剂量递增MHFRT与肠道生活质量下降的几率更高相关（OR 1.68，95%置信区间1.07 - 2.61；p = 0.023），但未发现有更多尿生活质量下降的证据（1.57，0.87 - 2.85；p = 0.13）。
与CFRT相比，等剂量MHFRT和剂量递增MHFRT的疗效相似，但剂量递增MHFRT与医生评分及患者报告的肠道毒性更高相关。等剂量方案，例如20次分割给予60 Gy，应成为局限性前列腺癌的标准MHFRT方案。
无。
