輔助放療不能改善局部晚期前列腺癌患者的無事件生存率
作者：
小柯機器人發布時間：2020/9/30 15:26:26
英國倫敦大學學院醫院Claire L Vale團隊對局部晚期前列腺癌輔助放療或早期搶救性放療進行了一項前瞻性計劃系統評價和薈萃分析。2020年9月28日，該研究發表在《柳葉刀》雜誌上。
目前尚不清楚根治性前列腺切除術後輔助或早期搶救性放療是否更適合於患有局部或局部晚期前列腺癌的男性。為了對這些放療方案的隨機對照試驗進行前瞻性計劃系統評價，研究組對符合資格的試驗進行了適應性薈萃分析。
研究組檢索了截止到2020年7月8日的註冊試驗或會議記錄，篩選出比較中危或高危，局部或局部晚期前列腺癌男性（≥18歲）進行根治性前列腺切除術後，接受即時輔助放療或早期搶救性放療的隨機臨床試驗。
研究組使用無事件生存期的統一定義，即從隨機化到任何一種生化進展、放射學進展、開始非試驗治療、因前列腺癌死亡、或隨機分組後任意時間PSA水平至少為2.0 ng/mL的時間。
研究組最終確定了3項合格試驗，且可獲得2007年11月至2016年12月招募的2153例患者無事件生存的最新結果。中位隨訪時間從60個月至78個月不等，最長隨訪時間為132個月。1075例患者被隨機分配接受輔助放療，1078例接受早期搶救性放療，其中421例（39.1％）在分析時已開始治療，各組患者的臨床特徵保持平衡。
三項試驗中，參與者的中位年齡為64歲或65歲，大多數患者的格裡森評分為7分。所有試驗的偏倚風險均較低。基於270個事件，薈萃分析沒有證據表明輔助放療比早期搶救性放療能夠改善無事件生存率，風險比為0.95，而5年無事件生存率只有1個百分點變化（89％對88％）。各試驗結果一致。
研究結果表明，輔助放療不能改善局部或局部晚期前列腺癌男性的無事件生存率。
附：英文原文
Title: Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data
Author: Claire L Vale, David Fisher, Andrew Kneebone, Christopher Parker, Maria Pearse, Pierre Richaud, Paul Sargos, Matthew R Sydes, Christopher Brawley, Meryem Brihoum, Chris Brown, Sylvie Chabaud, Adrian Cook, Silvia Forcat, Carol Fraser-Browne, Igor Latorzeff, Mahesh K B Parmar, Jayne F Tierney
Issue&Volume: 2020-09-28
Abstract:
Background
It is unclear whether adjuvant or early salvage radiotherapy following radical prostatectomy is more appropriate for men who present with localised or locally advanced prostate cancer. We aimed to prospectively plan a systematic review of randomised controlled trials (RCTs) comparing these radiotherapy approaches.
Methods
We used a prospective framework for adaptive meta-analysis (FAME), starting the review process while eligible trials were ongoing. RCTs were eligible if they aimed to compare immediate adjuvant radiotherapy versus early salvage radiotherapy, following radical prostatectomy in men (age ≥18 years) with intermediate-risk or high-risk, localised or locally advanced prostate cancer. We searched trial registers and conference proceedings until July 8, 2020, to identify eligible RCTs. By establishing the ARTISTIC collaboration with relevant trialists, we were able to anticipate when eligible trial results would emerge, and we developed and registered a protocol with PROSPERO before knowledge of the trial results (CRD42019132669). We used a harmonised definition of event-free survival, as the time from randomisation until the first evidence of either biochemical progression (prostate-specific antigen [PSA] ≥0·4 ng/mL and rising after completion of any postoperative radiotherapy), clinical or radiological progression, initiation of a non-trial treatment, death from prostate cancer, or a PSA level of at least 2·0 ng/mL at any time after randomisation. We predicted when we would have sufficient power to assess whether adjuvant radiotherapy was superior to early salvage radiotherapy. Investigators supplied results for event-free survival, both overall and within predefined patient subgroups. Hazard ratios (HRs) for the effects of radiotherapy timing on event-free survival and subgroup interactions were combined using fixed-effect meta-analysis.
Findings
We identified three eligible trials and were able to obtain updated results for event-free survival for 2153 patients recruited between November, 2007, and December, 2016. Median follow-up ranged from 60 months to 78 months, with a maximum follow-up of 132 months. 1075 patients were randomly assigned to receive adjuvant radiotherapy and 1078 to a policy of early salvage radiotherapy, of whom 421 (39·1%) had commenced treatment at the time of analysis. Patient characteristics were balanced within trials and overall. Median age was similar between trials at 64 or 65 years (with IQRs ranging from 59 to 68 years) across the three trials and most patients (1671 [77·6%]) had a Gleason score of 7. All trials were assessed as having low risk of bias. Based on 270 events, the meta-analysis showed no evidence that event-free survival was improved with adjuvant radiotherapy compared with early salvage radiotherapy (HR 0·95, 95% CI 0·75–1·21; p=0·70), with only a 1 percentage point (95% CI 2 to 3) change in 5-year event-free survival (89% vs 88%). Results were consistent across trials (heterogeneity p=0·18; I 2=42%).
Interpretation
This collaborative and prospectively designed systematic review and meta-analysis suggests that adjuvant radiotherapy does not improve event-free survival in men with localised or locally advanced prostate cancer. Until data on long-term outcomes are available, early salvage treatment would seem the preferable treatment policy as it offers the opportunity to spare many men radiotherapy and its associated side-effects.
DOI: 10.1016/S0140-6736(20)31952-8
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31952-8/fulltext