英国伦敦大学学院Matthew R Sydes团队探讨了根治性前列腺切除术后放疗的时机。2020年9月28日，该研究发表在《柳叶刀》杂志上。
前列腺癌根治性前列腺切除术后放疗的最佳时机尚不确定。
为了比较辅助放疗与挽救性放疗的观察策略对前列腺特异性抗原（PSA）生化进展的疗效和安全性，2007年11月22日至2016年12月30日，研究组在加拿大、丹麦、爱尔兰和英国的试验中心进行了一项随机对照试验，招募了1396名至少有一项根治性前列腺切除术后生化进展危险因素的患者，即病理性T分期3或4，格里森评分为7-10，阳性切缘或术前PSA≥10ng/mL。
这些患者的平均年龄为65岁，将其按1：1随机分组，其中697例接受辅助放疗，699例接受挽救性放疗的观察策略，以评估PSA生化进展，即PSA≥0.1 ng/mL或连续三次升高。两组的一般临床特征均匹配。主要结局为无远端转移。
中位随访4.9年后，辅助放疗组中有649名（93％）患者在6个月内接受了放疗；挽救性放疗组中有228名（33％）在随机分组后的8年内接受了放疗。伴随着169次事件，辅助放疗组的5年无生化进展生存率为85%，挽救性放疗组为88%，无显著差异。
辅助放疗组5年内无非常规激素治疗率为93%，而挽救性放疗组为92%。辅助放疗组1年内自我报告的尿失禁情况比挽救性放疗组更为严重（平均评分为4.8分和4.0分），差异显著。辅助放疗组中有6％的参与者在2年内发生3-4级尿道狭窄，显著高于挽救性放疗组（4％）。
研究结果不支持根治性前列腺切除术后采用常规辅助放疗。辅助放疗会增加泌尿系统疾病的风险。
附：英文原文
Title: Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial
Author: Christopher C Parker, Noel W Clarke, Adrian D Cook, Howard G Kynaston, Peter Meidahl Petersen, Charles Catton, William Cross, John Logue, Wendy Parulekar, Heather Payne, Rajendra Persad, Holly Pickering, Fred Saad, Juliette Anderson, Amit Bahl, David Bottomley, Klaus Brasso, Rohit Chahal, Peter W Cooke, Ben Eddy, Stephanie Gibbs, Chee Goh, Sandeep Gujral, Catherine Heath, Alastair Henderson, Ramasamy Jaganathan, Henrik Jakobsen, Nicholas D James, Subramanian Kanaga Sundaram, Kathryn Lees, Jason Lester, Henriette Lindberg, Julian Money-Kyrle, Stephen Morris, Joe OSullivan, Peter Ostler, Lisa Owen, Prashant Patel, Alvan Pope, Richard Popert, Rakesh Raman, Martin Andreas Rder, Ian Sayers, Matthew Simms, Jim Wilson, Anjali Zarkar, Mahesh K B Parmar, Matthew R Sydes
Issue&Volume: 2020-09-28
Abstract:
Background
The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression.
Methods
We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7–10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047.
Findings
Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60–68). Median follow-up was 4·9 years (IQR 3·0–6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81–1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58–1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3–4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020).
Interpretation
These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy.
DOI: 10.1016/S0140-6736(20)31553-1
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31553-1/fulltext
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