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,The Lancet

当前位置： X-MOL 学术 › Lancet › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

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
The Lancet ( IF 168.9 ) Pub Date : 2022-05-12 , DOI: 10.1016/s0140-6736(21)01790-6
Alan Pollack ₁ , Theodore G Karrison ₂ , Alexander G Balogh ₃ , Leonard G Gomella ₄ , Daniel A Low ₅ , Deborah W Bruner ₆ , Jeffrey S Wefel ₇ , Andre-Guy Martin ₈ , Jeff M Michalski ₉ , Steve J Angyalfi ₃ , Himanshu Lukka ₁₀ , Sergio L Faria ₁₁ , George B Rodrigues ₁₂ , Marie-Claude Beauchemin ₁₃ , R Jeffrey Lee ₁₄ , Samantha A Seaward ₁₅ , Aaron M Allen ₁₆ , Drew C Monitto ₁₇ , Wendy Seiferheld ₁₈ , Oliver Sartor ₁₉ , Felix Feng ₂₀ , Howard M Sandler ₂₁

Affiliation

Department of Radiation Oncology, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA.
Department of Public Health Sciences, University of Chicago, Chicago, IL, USA; NRG Oncology, Philadelphia, PA, USA.
Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada.
Sidney Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA, USA.
Department of Radiation Oncology, University of California at Los Angeles, Los Angeles, CA, USA.
Nell Hodgson Woodruff School of Nursing, and Winship Cancer Institute at Emory University, Atlanta, GA, USA.
Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
CHU de Quebec-Université Laval (L'Hotel-Dieu de Quebec), Quebec, QC, Canada.
Department of Radiation Oncology, Washington University School of Medicine, St Louis, MO, USA.
Department of Oncology, McMaster University, Hamilton, ON, Canada.
McGill University Health Centre, Montreal, QC, Canada.
Department of Oncology, London Regional Cancer Program, Western University, London, ON, Canada.
Department of Radiation Oncology, CHUM-Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
Intermountain Medical Center, Salt Lake City, UT, USA.
Kaiser Permanente-Vallejo, Vallejo, CA, USA.
Davidoff Center, Rabin Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Spartanburg Regional Medical Center, Spartanburg, SC, USA.
NRG Oncology, Philadelphia, PA, USA.
Department of Medicine, Tulane University, New Orleans, LA, USA.
Department of Radiation Oncology, University of California at San Francisco, San Francisco, CA , USA.
Cedars Sinai Medical Center, Los Angeles, CA, USA.

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.

Funding

National Cancer Institute.

中文翻译：

将雄激素剥夺疗法和盆腔淋巴结治疗加入前列腺床补救放疗 (NRG Oncology/RTOG 0534 SPPORT)：国际、多中心、随机 3 期试验

背景

在因前列腺癌进行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) 可使约 70% 的患者在 5 年时无进展。一项三组随机试验旨在确定是否可以通过在 PBRT 中加入 4-6 个月的短期雄激素剥夺疗法 (ADT) 或短期 ADT 和盆腔淋巴结放疗来增加患者预后(PLNRT) 到 PBRT。

方法

这项国际性、多中心、随机、对照的 SPPORT 试验在美国、加拿大和以色列的 283 个放射肿瘤治疗中心进行。符合条件的患者（年龄≥18 岁）是因前列腺癌进行前列腺切除术后 PSA 持续可检测或最初不可检测且升高的 PSA 在 0·1 和 2·0 ng/mL 之间的患者。如果没有淋巴结受累的临床或病理证据，则接受和不接受淋巴结切除术 (N0/Nx) 的患者均符合条件。其他资格标准包括 pT2 或 pT3 疾病、前列腺切除术 Gleason 评分为 9 或更低，以及 Zubrod 体能状态为 0-1。符合条件的患者被随机分配接受单独 PBRT，剂量为 64·8–70·2 Gy，每日每次 1·8 Gy（第 1 组），PBRT 加短期 ADT（第 2 组），或 PLNRT（45 Gy每次分次 1·8 Gy，然后对剩余的 19·8–25·2 Gy) 加 PBRT 加短期 ADT（第 3 组）的计划目标体积进行减容。主要终点是无进展，其中进展被定义为根据 Phoenix 定义的生化失败（PSA ≥ 2 ng/mL 超过最低 PSA）、临床失败（局部、区域或远处）或任何原因死亡. 计划对 1191 名患者进行中期分析，最短潜在随访时间为 5 年，应用 p<0·001（单侧）的 Haybittle-Peto 边界来比较治疗组之间的 5 年无进展率。该试验已在 ClinicalTrials.gov 注册，NCT00567580。试验的主要目标已经完成，但长期随访仍在继续。

发现

2008 年 3 月 31 日至 2015 年 3 月 30 日期间，1792 名符合条件的患者被纳入并随机分配到三个治疗组（592 名分配至第 1 组 [仅 PBRT]，602 名分配至第 2 组 [PBRT 加短期 ADT]，598 名第 3 组 [PLNRT 加 PBRT 加短期 ADT]）。随后发现 76 名不合格的患者被排除在分析之外；因此，可评估的患者群体包括 1716 名患者。在中期分析中（n=1191 名患者；数据截止日期为 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 边界（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界限 (p=0·0063)。在中期分析（最终计划分析；数据截止 2021 年 5 月 26 日）之外进行额外的后续行动，在 8·2 年（IQR 6·6–9·4）幸存者的中位随访中，所有 1716 名符合条件的患者的 5 年无进展率为 70·9%（95% CI 67·0–第 1 组 74·9)，第 2 组 81·3% (78·0–84·6)，第 3 组 87·4% (84·7–90·2)。根据方案标准，无进展第 3 组优于第 1 组和第 2 组。第 3 组（563 名患者中的 246 [44%]）的急性（放疗后≤3 个月）2 级或更严重的不良事件明显多于第 2 组（201 [36 %] 的 563 人；p=0·0034），这又比第 1 组更常见（547 人的 98 [18%]；p<0·0001）。对于 3 级或更严重的不良事件也观察到了类似的发现。然而，晚期毒性（放疗后 > 3 个月）在各组之间没有显着差异，