在前列腺癌前列腺切除术后检测到前列腺特异性抗原(PSA)水平的男性中，挽救性前列腺床放射治疗(PBRT)在5年内使约70%的患者无进展。

这项国际、多中心、随机、对照的SPPORT试验在美国、加拿大和以色列的283个放射肿瘤癌症治疗中心进行。设计了一项三组随机试验，以确定在PBRT中加入4-6个月的短期雄激素剥夺疗法(ADT)，或在PBRT中同时加入短期ADT和盆腔淋巴结放疗(PLNRT)，是否能增加患者的预后。

在2008年3月31日至2015年3月30日期间，1792例符合条件的患者被随机分配到三个治疗组(第1组592例[单独PBRT]，第2组602例[PBRT +短期ADT]，第3组598例[PLNRT + PBRT +短期ADT])。76名随后被发现不符合条件的患者被排除在分析之外;因此，可评价患者群体包括1716例患者。在中期分析中(n=1191例患者;数据截止2018年5月23日)，当组1与组3比较时，超过了5年无进展的Haybittle-Peto边界(差异17.9%，误差2.9%;术;0·0001)。2组与3组的差异均未超过界限(p=0·0063)。除中期分析(最终计划的分析;在存活者8·2年的中位随访中(IQR为6·6-9·4)，所有1716名符合条件的患者的5年无进展率在第1组为70.9% (95% CI为67·0- 74.9)，第2组为81.3%(78·0- 84.6)，第3组为84.4%(87.7 -90·2)。根据协议标准，组3的进展自由优于组1和组2。急性(放疗后3个月)2级或更严重不良事件在第3组(563例患者中有246例[44%])明显比第2组(563例患者中有201例[36%];P =0·0034)，这比第1组更常见(547例中有98例[18%];术;0·0001)。在3级或更严重的不良事件中观察到类似的结果。然而，晚期毒性(放疗后3个月)在两组之间没有显著差异，除3组比2组更多的晚期2级或更糟的血液或骨髓事件(单侧p=0·0060)，这是由于该组中添加了PLNRT。

Abstract

Background: In men with a detectable prostate-specific antigen (PSA) level after prostatectomy for prostate cancer, salvage prostate bed radiotherapy (PBRT) results in about 70% of patients being free of progression at 5 years. A three-group randomised trial was designed to determine whether incremental gains in patient outcomes can be achieved by adding either 4-6 months of short-term androgen deprivation therapy (ADT) to PBRT, or both short-term ADT and pelvic lymph node radiotherapy (PLNRT) to PBRT.

Methods: The international, multicentre, randomised, controlled SPPORT trial was done at 283 radiation oncology cancer treatment centres in the USA, Canada, and Israel. Eligible patients (aged ≥18 years) were those who after prostatectomy for adenocarcinoma of the prostate had a persistently detectable or an initially undetectable and rising PSA of between 0·1 and 2·0 ng/mL. Patients with and without lymphadenectomy (N0/Nx) were eligible if there was no clinical or pathological evidence of lymph node involvement. Other eligibility criteria included pT2 or pT3 disease, prostatectomy Gleason score of 9 or less, and a Zubrod performance status of 0-1. Eligible patients were randomly assigned to receive PBRT alone at a dose of 64·8-70·2 Gy at 1·8 Gy per fraction daily (group 1), PBRT plus short-term ADT (group 2), or PLNRT (45 Gy at 1·8 Gy per fraction, and then a volume reduction made to the planning target volume for the remaining 19·8-25 ·2 Gy) plus PBRT plus short-term ADT (group 3). The primary endpoint was freedom from progression, in which progression was defined as biochemical failure according to the Phoenix definition (PSA ≥2 ng/mL over the nadir PSA), clinical failure (local, regional, or distant), or death from any cause. A planned interim analysis of 1191 patents with minimum potential follow-up time of 5 years applied a Haybittle-Peto boundary of p<0·001 (one sided) for comparison of 5-year freedom from progression rates between the treatment groups. This trial is registered with ClinicalTrials.gov, NCT00567580. The primary objectives of the trial have been completed, although long-term follow-up is continuing.

Findings: Between March 31, 2008, and March 30, 2015, 1792 eligible patients were enrolled and randomly assigned to the three treatment groups (592 to group 1 [PBRT alone], 602 to group 2 [PBRT plus short-term ADT], and 598 to group 3 [PLNRT plus PBRT plus short-term ADT]). 76 patients subsequently found to be ineligible were excluded from the analyses; thus, the evaluable patient population comprised 1716 patients. At the interim analysis (n=1191 patients; data cutoff May 23, 2018), the Haybittle-Peto boundary for 5-year freedom from progression was exceeded when group 1 was compared with group 3 (difference 17·9%, SE 2·9%; p<0·0001). The difference between groups 2 and 3 did not exceed the boundary (p=0·0063). With additional follow-up beyond the interim analysis (the final planned analysis; data cutoff May 26, 2021), at a median follow-up among survivors of 8·2 years (IQR 6·6-9·4), the 5-year freedom from progression rates in all 1716 eligible patients were 70·9% (95% CI 67·0-74·9) in group 1, 81·3% (78·0-84·6) in group 2, and 87·4% (84·7-90·2) in group 3. Per protocol criteria, freedom from progression in group 3 was superior to groups 1 and 2. Acute (≤3 months after radiotherapy) grade 2 or worse adverse events were significantly more common in group 3 (246 [44%] of 563 patients) than in group 2 (201 [36%] of 563; p=0·0034), which, in turn, were more common than in group 1 (98 [18%] of 547; p<0·0001). Similar findings were observed for grade 3 or worse adverse events. However, late toxicity (>3 months after radiotherapy) did not differ significantly between the groups, apart from more late grade 2 or worse blood or bone marrow events in group 3 versus group 2 (one-sided p=0·0060) attributable to the addition of PLNRT in this group.

Interpretation: The results of this randomised trial establish the benefit of adding short-term ADT to PBRT to prevent progression in prostate cancer. To our knowledge, these are the first such findings to show that extending salvage radiotherapy to treat the pelvic lymph nodes when combined with short-term ADT results in meaningful reductions in progression after prostatectomy in patients with prostate cancer.

原文链接

pubmed.ncbi.nlm.nih.gov/35320644/

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