ImportanceNo prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy.ObjectiveTo determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years.Design, Setting, and ParticipantsIn this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed.InterventionPatients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT).Main Outcomes and MeasuresThe coprimary end points were the 2-year change in score from baseline for the bowel and urinary domains of the Expanded Prostate Cancer Composite Index questionnaire. Secondary objectives were to compare between arms freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer–specific survival, overall survival, and adverse events.ResultsOf the 296 patients randomized (median [range] age, 65 [44-81] years; 100% male), 144 received HYPORT and 152 received COPORT. At the end of RT, the mean GU change scores among those in the HYPORT and COPORT arms were neither clinically significant nor different in statistical significance and remained so at 6 and 12 months. The mean (SD) GI change scores for HYPORT and COPORT were both clinically significant and different in statistical significance at the end of RT (−15.52 [18.43] and −7.06 [12.78], respectively; P < .001). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months. The 24-month differences in mean GU and GI change scores for HYPORT were noninferior to COPORT using noninferiority margins of −5 and −6, respectively, rejecting the null hypothesis of inferiority (mean [SD] GU score: HYPORT, −5.01 [15.10] and COPORT, −4.07 [14.67]; P = .005; mean [SD] GI score: HYPORT, −4.17 [10.97] and COPORT, −1.41 [8.32]; P = .02). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure, defined as a PSA of 0.4 ng/mL or higher and rising (2-year rate, 12% vs 8%; P = .28).Conclusions and RelevanceIn this randomized clinical trial, HYPORT was associated with greater patient-reported GI toxic effects compared with COPORT at the completion of RT, but both groups recovered to baseline levels within 6 months. At 2 years, HYPORT was noninferior to COPORT in terms of patient-reported GU or GI toxic effects. HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy.Trial RegistrationClinicalTrials.gov Identifier: NCT03274687

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大分割与传统前列腺切除术后放疗治疗泌尿生殖和胃肠道症状的非劣效性

重要性之前没有试验在主要接受前列腺切除术治疗的患者中比较大分割前列腺切除术后放疗 (HYPORT) 与传统分割前列腺切除术后 (COPORT)。 目的确定对于患者报告的 2 年泌尿生殖 (GU) 和胃肠道 (GI) 症状，HYPORT 是否不劣于 COPORT设计、设置和参与者在这项 3 期随机临床试验中，患有 pT2/3pNX/0 疾病的前列腺切除术后可检测到前列腺特异性抗原（PSA；≥0.1 ng/mL）或未检测到 PSA（<0.1 ng/mL）的患者/mL) 的 pT3 疾病或 pT2 疾病且手术切缘呈阳性的患者是从美国和加拿大的 93 个学术、社区和三级医疗机构招募的。2017年6月至2018年7月期间，共有296名患者被随机分组​​。数据于 2020 年 12 月进行分析，之后根据需要进行额外分析。干预患者被随机分配接受 62.5 Gy 25 次剂量 (HYPORT) 或 66.6 Gy 37 次剂量 (COPORT)。主要结果和措施共同主要终点是 2 年扩展前列腺癌综合指数调查问卷的肠道和泌尿领域评分相对于基线的变化。次要目标是比较各组之间的生化失败率、进展时间、局部失败、区域失败、抢救治疗、远处转移、前列腺癌特异性生存率、总体生存率和不良事件。 结果 296 名随机患者（中位数[范围] ] 年龄，65 [44-81] 岁；100% 男性），144 人接受了 HYPORT，152 人接受了 COPORT。RT 结束时，HYPORT 组和 COPORT 组的平均 GU 变化评分既没有临床意义，也没有统计显着性差异，并且在 6 个月和 12 个月时仍然如此。HYPORT 和 COPORT 的平均 (SD) GI 变化评分均具有临床显着性，并且在 RT 结束时具有不同的统计显着性（分别为 -15.52 [18.43] 和 -7.06 [12.78]；磷< .001）。然而，HYPORT 和 COPORT 平均 GI 变化评分的临床和统计学显着差异在 6 个月和 12 个月时得到解决。HYPORT 的平均 GU 和 GI 变化评分的 24 个月差异不劣于 COPORT，非劣效界限分别为 -5 和 -6，拒绝了劣效的零假设（平均 [SD] GU 评分：HYPORT，-5.01 [15.10 ] 和 COPORT，-4.07 [14.67]；磷= .005；平均 [SD] GI 评分：HYPORT，-4.17 [10.97] 和 COPORT，-1.41 [8.32]；磷= .02)。对审查患者的中位随访时间为 2.1 年，HYPORT 与 COPORT 之间的生化失败（定义为 PSA 为 0.4 ng/mL 或更高并且不断上升）之间没有差异（2 年率，12% vs 8%；磷= .28)。结论和相关性在这项随机临床试验中，与 COPORT 相比，在 RT 完成时，HYPORT 与患者报告的更大的胃肠道毒性作用相关，但两组均在 6 个月内恢复到基线水平。2 年时，就患者报告的 GU 或 GI 毒性作用而言，HYPORT 不劣于 COPORT。HYPORT 是接受前列腺切除术后放疗的患者可接受的新实践标准。试验注册ClinicalTrials.gov 标识符：NCT03274687