Nikitas John, Jamshidian Parsa, Tree Alison C, Hall Emma, Dearnaley David, Michalski Jeff M, Lee W Robert, Nguyen Paul L, Sandler Howard M, Catton Charles N, Lukka Himanshu R, Incrocci Luca, Heemsbergen Wilma, Pos Floris J, Roy Soumyajit, Malone Shawn, Horwitz Eric, Wong Jessica Karen, Arcangeli Stefano, Sanguineti Giuseppe, Romero Tahmineh, Sun Yilun, Steinberg Michael L, Valle Luca F, Weidhaas Joanne B, Spratt Daniel, Telesca Donatello, Kishan Amar U
Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.
Department of Biostatistics, University of California, Los Angeles, Los Angeles, CA, USA.
Lancet Oncol. 2025 Mar;26(3):378-386. doi: 10.1016/S1470-2045(24)00720-4. Epub 2025 Jan 30.
The association between acute and late toxicity following prostate radiotherapy has not been well studied using data from multiple randomised clinical trials and fractionation schedules. We aimed to characterise the relationship between acute and late genitourinary and gastrointestinal toxicity among patients receiving conventionally fractionated or moderately hypofractionated prostate radiotherapy.
This was an individual patient data meta-analysis that identified randomised phase 3 trials of conventionally fractionated or moderately hypofractionated prostate radiotherapy in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium that had individual-level acute and late toxicity data available and were available before Dec 1, 2023. Trials without individual patient data were excluded. Data were provided to MARCAP by study investigators. The associations between acute (≤3 months after radiotherapy) and late (>3 months after radiotherapy) grade 2 or greater genitourinary and gastrointestinal toxicities were assessed using adjusted generalised linear mixed models (adjusted for age, androgen deprivation therapy status, type of radiotherapy, radiation dose, and radiation schedule). In the subset of trials that collected Expanded Prostate Cancer Index Composite quality of life (QOL) evaluations, the association between acute genitourinary and gastrointestinal toxicity and decrements at least twice the minimal clinically important difference (MCID) for urinary and bowel QOL were also evaluated.
Six of 26 available trials met all the eligibility criteria. 6593 patients were included (conventionally fractionated: n=4248; moderately hypofractionated: n=2345). Median follow-up was 72 months (IQR 61-94). Acute grade 2 or greater genitourinary toxicity was associated with both late grade 2 or greater genitourinary toxicity (odds ratio 2·20 [95% CI 1·88-2·57], p<0·0001) and decrement at least twice the MCID in urinary QOL (1·41 [1·17-1·68], p=0·0002). Acute grade 2 or greater gastrointestinal toxicity was associated with both late grade 2 or greater gastrointestinal toxicity (2·53 [2·07-3·08], p<0·0001) and decrement at least twice the MCID in bowel QOL (1·52 [1·26-1·83], p<0·0001).
Acute toxicity following prostate radiotherapy was statistically significantly associated with late toxicity and with decrement in patient-reported QOL metrics. These data support efforts to evaluate whether interventions that reduce acute toxicity ultimately reduce the risk of late toxicity.
National Institutes of Health and US Department of Defense.
利用来自多个随机临床试验和分割方案的数据，对前列腺放疗后的急性毒性和晚期毒性之间的关联尚未进行充分研究。我们旨在描述接受常规分割或适度低分割前列腺放疗的患者中，急性和晚期泌尿生殖系统及胃肠道毒性之间的关系。
这是一项个体患者数据荟萃分析，在前列腺癌随机试验荟萃分析（MARCAP）联盟中，识别出常规分割或适度低分割前列腺放疗的随机3期试验，这些试验有个体水平的急性和晚期毒性数据，且在2023年12月1日前可获取。没有个体患者数据的试验被排除。研究调查人员将数据提供给MARCAP。使用调整后的广义线性混合模型（根据年龄、雄激素剥夺治疗状态、放疗类型、辐射剂量和放疗方案进行调整），评估放疗后≤3个月的急性和放疗后>3个月的2级或更高级别的泌尿生殖系统和胃肠道毒性之间的关联。在收集了扩展前列腺癌指数综合生活质量（QOL）评估的试验子集中，还评估了急性泌尿生殖系统和胃肠道毒性与泌尿和肠道QOL至少下降两倍最小临床重要差异（MCID）之间的关联。
26项可用试验中的6项符合所有纳入标准。纳入6593例患者（常规分割：n = 4248；适度低分割：n = 2345）。中位随访时间为72个月（IQR 61 - 94）。急性2级或更高级别的泌尿生殖系统毒性与晚期2级或更高级别的泌尿生殖系统毒性相关（优势比2.20 [95% CI 1.88 - 2.57]，p < 0.0001），且与泌尿QOL至少下降两倍MCID相关（1.41 [1.17 - 1.68]，p = 0.0002）。急性2级或更高级别的胃肠道毒性与晚期2级或更高级别的胃肠道毒性相关（2.53 [2.07 - 3.08]，p < 0.0001），且与肠道QOL至少下降两倍MCID相关（1.52 [1.26 - 1.83]，p < 0.0001）。
前列腺放疗后的急性毒性与晚期毒性以及患者报告的QOL指标下降在统计学上显著相关。这些数据支持评估降低急性毒性的干预措施是否最终能降低晚期毒性风险的努力。
美国国立卫生研究院和美国国防部。
