美国迈阿密大学米勒医学院和希尔维斯特癌症中心Alan Pollack团队研究了挽救性前列腺床放疗加雄激素剥夺治疗和盆腔淋巴结治疗前列腺癌术后患者对其预后的影响。相关论文于2022年5月14日发表在《柳叶刀》杂志上。

在前列腺癌前列腺切除术后可检测到前列腺特异性抗原（PSA）水平的男性中，挽救性前列腺床放疗（PBRT）可导致约70%的患者在5年后无进展。一项三组随机试验旨在确定是否可通过在PBRT中添加4-6个月的短期雄激素剥夺疗法（ADT）或在PBRT中同时添加短期ADT和盆腔淋巴结放疗（PLNRT）来改善患者预后。

研究组在美国、加拿大和以色列的283个放射肿瘤癌症治疗中心进行了一项国际性、多中心、随机、对照的SPPORT试验。符合条件的成人（≥18岁）患者中，前列腺癌切除术后PSA持续可检测或最初不可检测，且PSA升高在0.1-2.0 ng/mL之间。若没有淋巴结受累的临床或病理证据，则进行和未进行淋巴结切除术（N0/Nx）的患者符合条件。其他资格标准还包括pT2或pT3疾病，前列腺切除术Gleason评分为9分或以下，Zubrod表现状态为0-1。

将符合条件的患者随机分配，分别接受PBRT（第1组），PBRT加短期ADT（第2组），或PLNRT加上PBRT+短期ADT（第3组）。主要终点是无进展，根据菲尼克斯定义（PSA），进展被定义为生化失败（PSA≥2 ng/mL），临床失败（局部、区域或远处），或全因死亡。研究组计划对1191例患者进行中期分析，最短潜在随访时间为5年，比较治疗组之间5年无进展率。试验的主要目标已完成，但长期随访仍在继续。

2008年3月31日至2015年3月30日，1792名符合条件的患者被登记并随机分配到三个治疗组，其中第1组592名、第2组602名、第3组598名。76名后续发现不合格的患者被排除在分析之外；因此，可评估患者群体包括1716名患者。在中期分析中（1191名患者；数据截止日期2018年5月23日），当第1组与第3组进行比较时，超过了5年无进展的Haybittle-Peto边缘（差异17.9%，SE 2.9%；p<0.0001）。

第2组和第3组之间的差异没有超过边缘值。在中期分析（最终计划分析；数据截止日期2021年5月26日）之外的额外随访中，即中位8.2年的随访中，所有1716名合格患者的5年无进展率在第1组为70.9%，第2组为81.3%，第3组为87.4%。根据方案标准，第3组的无进展率优于第1组和第2组。

第3组中急性（≤放疗后3个月）2级及以上不良事件的发生率（563例患者中246例[44%]）明显高于第2组（563例患者中201例[36%]），而第2组的发生率也显著高于第1组（547例患者中98例[18%]）。3级及以上不良事件也有类似的发现。然而，除第2组中由于添加PLNRT而导致的晚期2级及以上的血液或骨髓事件外，第3组与第2组间的晚期毒性（放疗后>3个月）没有显著差异。

这项随机试验的结果证实了在PBRT中加入短期ADT预防前列腺癌进展的益处。这些发现首次表明，在前列腺癌患者前列腺切除术后，延长补救性放疗治疗盆腔淋巴结，并结合短期ADT，可显著减少进展。

附：英文原文

Title: The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial

Author: Alan Pollack, Theodore G Karrison, Alexander G Balogh, Leonard G Gomella, Daniel A Low, Deborah W Bruner, Jeffrey S Wefel, Andre-Guy Martin, Jeff M Michalski, Steve J Angyalfi, Himanshu Lukka, Sergio L Faria, George B Rodrigues, Marie-Claude Beauchemin, R Jeffrey Lee, Samantha A Seaward, Aaron M Allen, Drew C Monitto, Wendy Seiferheld, Oliver Sartor, Felix Feng, Howard M Sandler

Issue&Volume: 2022/05/14

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.

DOI: 10.1016/S0140-6736(21)01790-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01790-6/fulltext