中国人群前列腺癌根治术后切缘阳性危险因素的Meta分析

doi:10.12114/j.issn.1007-9572.2022.0568

摘要/Abstract

摘要： 背景前列腺癌是危害我国老年男性生命健康常见的恶性肿瘤之一，前列腺癌根治术是局限性前列腺癌治疗最主要的手段。然而，部分患者存在术后病理标本切缘阳性，而切缘阳性是术后生化复发的高风险指标，是预后不良的高风险因素。目前有关中国人群前列腺癌根治术后切缘阳性的危险因素尚无统一意见。目的探讨中国人群前列腺癌根治术后切缘阳性的危险因素，为防控工作提供参考。方法计算机检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据知识服务平台、中国生物医学文献数据库和维普网，搜集有关中国人群前列腺癌根治术后切缘阳性危险因素的相关文献，检索时限均从建库至2022-03-01，使用纽卡斯尔-渥太华量表（NOS）评价队列研究质量。采用Stata 16.0统计学软件对纳入研究的数据进行Meta分析。结果最终纳入21篇病例对照研究，包括6 782例患者，其中切缘阳性患者2 028例。Meta分析结果显示，术前高前列腺特异抗原（PSA）〔OR=1.77，95%CI（1.18，2.65）〕、穿刺神经周围侵犯〔OR=5.83，95%CI（2.05，16.59）〕、术前高级别临床T分期〔OR=2.17，95%CI（1.06，4.42）〕、术后高级别病理T分期〔OR=4.30，95%CI（2.43，7.63）〕、高穿刺阳性针数百分比〔OR=1.83，95%CI（1.35，2.47）〕、高穿刺格里森（Gleason）评分〔OR=2.14，95%CI（1.67，2.74）〕、术后高Gleason评分〔OR= 2.33，95%CI（1.80，3.01）〕是我国人群前列腺癌根治术后切缘阳性的危险因素（P<0.05）。不同的手术方式的亚组分析显示，术前高级别临床T分期〔OR=4.57，95%CI（2.57，8.12）〕、术后高级别病理T分期〔OR=4.80，95%CI（2.20，10.48）〕，术后高Gleason评分〔OR=2.46，95%CI（1.57，3.86）〕是行腹腔镜下根治性前列腺切除术的前列腺癌患者切缘阳性的危险因素（P<0.05）；术前高PSA〔OR=2.17，95%CI（1.60，2.94）〕是行机器人辅助腹腔镜根治性前列腺切除术的前列腺癌患者切缘阳性的危险因素（P<0.05）。敏感性分析结果显示，危险因素的一致性均较好，结果具有稳定性；术前PSA、术后病理T分期和术后Gleason评分的漏斗图分布不对称，存在发表偏倚；术前临床T分期漏斗图分布对称，不存在发表偏倚。结论 PSA、穿刺神经周围侵犯、术前高级别临床T分期、术后高级别病理T分期、高穿刺阳性针数百分比、高穿刺Gleason评分、术后高Gleason评分是我国人群前列腺癌根治术后切缘阳性的危险因素，在临床工作中应尽早识别，并采取干预措施来预防肿瘤复发和进展。

关键词: 前列腺肿瘤, 前列腺癌根治术, 切缘阳性, 术后并发症, 危险因素, Meta分析

Abstract:

Background

Prostate cancer is one of the most prevalent cancers that endangers the live and health of elderly Chinese men. Currently, radical prostatectomy (RP) is the predominant treatment for localized prostate cancer, but postoperative positive surgical margins (PSMs) have been detected pathologically in some cases. Studies have shown that PSMs indicate high probability of biochemical recurrence and poor prognosis after RP. There is no consensus of risk factors for PSMs after RP in Chinese men.

Objective

To perform a meta-analysis of risk factors for PSMs after RP in Chinese men, providing evidence for the containment of PSMs.

Methods

Databases of PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Wanfang Data, CBM and VIP were searched to collect literature on risk factors for PSMs after RP in Chinese men from the time of database creation to March 1, 2022. The Newcastle-Ottawa scale was adopted to assess the quality of included cohort studies. Stata 16.0 was used to perform meta-analysis.

Results

Twenty-one case-control studies were enrolled, including 6 782 patients, among whom 2 028 had PSMs. Meta-analysis indicated that high pre-RP prostate specific antigen (PSA) 〔OR=1.77, 95%CI (1.18, 2.65) 〕, perineural invasion at puncture time〔OR=5.83, 95%CI (2.05, 16.59) 〕, pre-RP clinical stage T3 or T4〔OR=2.17, 95%CI (1.06, 4.42) 〕, post-RP pathological stage T3 or T4 〔OR=4.30, 95%CI (2.43, 7.63) 〕, high percentage of positive puncture stitches〔OR=1.83, 95%CI (1.35, 2.47) 〕, high Gleason score at the time of puncture〔OR=2.14, 95%CI (1.67, 2.74) 〕, and high Gleason score after RP〔OR=2.33, 95%CI (1.80, 3.01) 〕were risk factors for PSMs after RP (P<0.05) . Subgroup analysis of different surgical approaches in RP showed that pre-RP clinical stage T3 or T4 〔OR=4.57, 95%CI (2.57, 8.12) 〕, post-RP pathological stage T3 or T4 〔OR=4.80, 95%CI (2.20, 10.48) 〕, and high Gleason score after RP〔OR=2.46, 95%CI (1.57, 3.86) 〕were risk factors for PSMs treated with laparoscopic RP (P<0.05) . But in robot-assisted RP, the risk factor was high pre-RP PSA 〔OR=2.17, 95%CI (1.60, 2.94) 〕 (P<0.05) . Sensitivity analysis demonstrated that there was high-level agreement on risks for PSMs in these studies, and the results of meta-analysis was robust. Asymmetric funnel plots showed potential publication bias for the meta-analysis of the impact of pre-RP PSA, post-RP pathological T stage and Gleason score on PSMs, while symmetric funnel plot showed no potential publication bias for the meta-analysis of the impact of pre-RP clinical T stage on PSMs.

Conclusion

PSA, perineural invasion at puncture time, pre-RP clinical stage T3 or T4, post-RP pathological stage T3 or T4, high percentage of positive puncture stitches, high Gleason score at the time of puncture, and high Gleason score after RP were risk factors for PSMs after RP, which should be early recognized and addressed to halt tumor growth and recurrence.

Key words: Prostatic neoplasms, Radical prostatectomy, Positive surgical margin, Postoperative complications, Risk factors, Meta-analysis

靳通通,吴王剑,付豪,等. 中国人群前列腺癌根治术后切缘阳性危险因素的Meta分析[J]. 中国全科医学, 2023, 26(17): 2147-2154. DOI: 10.12114/j.issn.1007-9572.2022.0568.
JIN Tongtong,WU Wangjian,FU Hao, et al. Risk Factors for Positive Surgical Margins after Radical Prostatectomy in Chinese Men: a Meta-analysis[J]. Chinese General Practice, 2023, 26(17): 2147-2154. DOI: 10.12114/j.issn.1007-9572.2022.0568.

图/表 18

参考文献 36

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步骤	检索词
#1	（ "Prostatectomy" [Title/Abstract] OR "Prostatectomies" [Title/Abstract] OR "suprapubic prostatectomies" [Title/Abstract] OR "suprapubic prostatectomy " [Title/Abstract] OR "retropubic prostatectomies" [Title/Abstract] OR "retropubic prostatectomy" [Title/Abstract] OR "radical prostatectomy" [Title/Abstract] OR（（ "radical" [All Fields] OR "radical's" [All Fields] OR "radicals" [All Fields]） AND（ "resect" [All Fields] OR "resectability" [All Fields] OR "resectable" [All Fields] OR "resectates" [All Fields] OR "resected" [All Fields] OR "resecting" [All Fields] OR "Resection" [All Fields] OR "resectional" [All Fields] OR "resectioned" [All Fields] OR "resectioning" [All Fields] OR "resections" [All Fields] OR "resective" [All Fields] OR "resects" [All Fields]） AND " prostate cancer" [Title/Abstract]））
#2	（ "positive margin" [Title/Abstract] OR "positive excision margins" [Title/Abstract] OR "margins of excision" [Title/Abstract] OR "excision margin" [Title/Abstract]　OR "excision margins" [Title/Abstract] OR "resection margin" [Title/Abstract] OR "resection margins" [Title/Abstract] OR "surgical margins" [Title/Abstract] OR "surgical margin" [Title/Abstract] OR "positive surgical margins" [Title/Abstract] OR "positive surgical margin" [Title/Abstract] OR "negative surgical margins" [Title/Abstract] OR "negative surgical margin" [Title/Abstract] OR "tumor free margins" [Title/Abstract] OR "tumor free margins" [Title/Abstract] OR "tumor free margin" [Title/Abstract]）
#3	（ "Risk factors" [Title/Abstract] OR "social risk factors" [Title/Abstract] OR "social risk factor" [Title/Abstract] OR "health correlates" [Title/Abstract] OR "population at risk" [Title/Abstract] OR "populations at risk" [Title/Abstract] OR "risk scores" [Title/Abstract] OR "risk score" [Title/Abstract] OR "risk factor scores" [Title/Abstract] OR "risk factor score" [Title/Abstract] OR "dangerous factor" [Title/Abstract] OR "hazardous factors" [Title/Abstract] OR "risky factors" [Title/Abstract] OR "risks factors" [Title/Abstract] OR "Risk-factors" [Title/Abstract] OR "danger factors" [Title/Abstract] OR "danger factor" [Title/Abstract] OR "hazard factors" [Title/Abstract] OR "Factor" [Title/Abstract] OR "Factors" [Title/Abstract] OR " elements" [Title/Abstract] OR "element" [Title/Abstract]）
#4	#1 AND #2 AND #3

步骤	检索词
#1	（ "Prostatectomy" [Title/Abstract] OR "Prostatectomies" [Title/Abstract] OR "suprapubic prostatectomies" [Title/Abstract] OR "suprapubic prostatectomy " [Title/Abstract] OR "retropubic prostatectomies" [Title/Abstract] OR "retropubic prostatectomy" [Title/Abstract] OR "radical prostatectomy" [Title/Abstract] OR（（ "radical" [All Fields] OR "radical's" [All Fields] OR "radicals" [All Fields]） AND（ "resect" [All Fields] OR "resectability" [All Fields] OR "resectable" [All Fields] OR "resectates" [All Fields] OR "resected" [All Fields] OR "resecting" [All Fields] OR "Resection" [All Fields] OR "resectional" [All Fields] OR "resectioned" [All Fields] OR "resectioning" [All Fields] OR "resections" [All Fields] OR "resective" [All Fields] OR "resects" [All Fields]） AND " prostate cancer" [Title/Abstract]））
#2	（ "positive margin" [Title/Abstract] OR "positive excision margins" [Title/Abstract] OR "margins of excision" [Title/Abstract] OR "excision margin" [Title/Abstract]　OR "excision margins" [Title/Abstract] OR "resection margin" [Title/Abstract] OR "resection margins" [Title/Abstract] OR "surgical margins" [Title/Abstract] OR "surgical margin" [Title/Abstract] OR "positive surgical margins" [Title/Abstract] OR "positive surgical margin" [Title/Abstract] OR "negative surgical margins" [Title/Abstract] OR "negative surgical margin" [Title/Abstract] OR "tumor free margins" [Title/Abstract] OR "tumor free margins" [Title/Abstract] OR "tumor free margin" [Title/Abstract]）
#3	（ "Risk factors" [Title/Abstract] OR "social risk factors" [Title/Abstract] OR "social risk factor" [Title/Abstract] OR "health correlates" [Title/Abstract] OR "population at risk" [Title/Abstract] OR "populations at risk" [Title/Abstract] OR "risk scores" [Title/Abstract] OR "risk score" [Title/Abstract] OR "risk factor scores" [Title/Abstract] OR "risk factor score" [Title/Abstract] OR "dangerous factor" [Title/Abstract] OR "hazardous factors" [Title/Abstract] OR "risky factors" [Title/Abstract] OR "risks factors" [Title/Abstract] OR "Risk-factors" [Title/Abstract] OR "danger factors" [Title/Abstract] OR "danger factor" [Title/Abstract] OR "hazard factors" [Title/Abstract] OR "Factor" [Title/Abstract] OR "Factors" [Title/Abstract] OR " elements" [Title/Abstract] OR "element" [Title/Abstract]）
#4	#1 AND #2 AND #3

第一作者	发表年份（年）	研究地区	样本量（例）		手术方式	结局指标	NOS评分（分）
第一作者	发表年份（年）	研究地区	病例组	对照组	手术方式	结局指标	NOS评分（分）
张靖博^[5]	2021	河南	64	188	LRP	①②⑦⑧	8
张平新^[6]	2020	新疆	26	73	LRP	⑧	6
阎乙夫^[7]	2011	北京	76	112	LRP	⑦⑧	8
陈星^[8]	2021	福建	36	86	LRP	①③④⑦⑧	7
张争^[9]	2019	北京	57	120	LRP	⑧	7
吴丹^[10]	2020	江苏	34	82	LRP	⑧	6
缪志俊^[11]	2021	江苏	79	420	LRP	①③⑤	7
王硕^[12]	2021	北京	97	83	—	⑦⑧	8
侯惠民^[13]	2018	北京	94	226	—	②	7
范效铮^[14]	2021	陕西	158	360	RARP	①⑤	8
屈武功^[15]	2021	河南	106	204	RARP	②	7
张春雷^[16]	2018	上海	47	143	RARP	①⑧	7
沈诞^[17]	2012	上海	258	1 390	RARP	⑤	7
瞿旻^[18]	2017	上海	151	249	RARP	①⑤	8
韩涛^[19]	2013	江苏	98	162	LRP	④⑥	6
张铁龙^[20]	2015	上海	61	184	ORP	①⑦	6
丁攀^[21]	2019	江西	118	114	—	①②④⑥	7
洪锴^[22]	2008	北京	9	24	LRP	⑤⑦	7
YANG^[23]	2017	江苏	86	210	LRP	③④⑥	7
WANG^[24]	2021	北京	106	94	—	④⑤	8
ZHOU^[25]	2021	天津	267	230	—	①⑦	8

第一作者	发表年份（年）	研究地区	样本量（例）		手术方式	结局指标	NOS评分（分）
第一作者	发表年份（年）	研究地区	病例组	对照组	手术方式	结局指标	NOS评分（分）
张靖博^[5]	2021	河南	64	188	LRP	①②⑦⑧	8
张平新^[6]	2020	新疆	26	73	LRP	⑧	6
阎乙夫^[7]	2011	北京	76	112	LRP	⑦⑧	8
陈星^[8]	2021	福建	36	86	LRP	①③④⑦⑧	7
张争^[9]	2019	北京	57	120	LRP	⑧	7
吴丹^[10]	2020	江苏	34	82	LRP	⑧	6
缪志俊^[11]	2021	江苏	79	420	LRP	①③⑤	7
王硕^[12]	2021	北京	97	83	—	⑦⑧	8
侯惠民^[13]	2018	北京	94	226	—	②	7
范效铮^[14]	2021	陕西	158	360	RARP	①⑤	8
屈武功^[15]	2021	河南	106	204	RARP	②	7
张春雷^[16]	2018	上海	47	143	RARP	①⑧	7
沈诞^[17]	2012	上海	258	1 390	RARP	⑤	7
瞿旻^[18]	2017	上海	151	249	RARP	①⑤	8
韩涛^[19]	2013	江苏	98	162	LRP	④⑥	6
张铁龙^[20]	2015	上海	61	184	ORP	①⑦	6
丁攀^[21]	2019	江西	118	114	—	①②④⑥	7
洪锴^[22]	2008	北京	9	24	LRP	⑤⑦	7
YANG^[23]	2017	江苏	86	210	LRP	③④⑥	7
WANG^[24]	2021	北京	106	94	—	④⑤	8
ZHOU^[25]	2021	天津	267	230	—	①⑦	8

危险因素	纳入研究数（篇）	异质性分析结果		效应模型	Meta分析结果
危险因素	纳入研究数（篇）	I²值（%）	P值	效应模型	OR（95%CI）	P值
LRP
术前PSA	3^[5,8,11]	87.7	<0.001	随机效应模型	1.47（0.42，5.09）	0.548
穿刺阳性针数	3^[8,11,23]	84.3	0.002	随机效应模型	2.17（0.98，4.80）	0.057
术前临床T分期	2^[11,22]	43.9	0.182	固定效应模型	4.57（2.57，8.12）	<0.001
术后病理T分期	6^{[5,6,7,8,9,10]}	79.2	<0.001	随机效应模型	4.80（2.20，10.48）	<0.001
术后Gleason评分	3^[5,7,8]	0	0.739	固定效应模型	2.46（1.57，3.86）	<0.001
RARP
术前PSA	3^[14,16,18]	22.4	0.275	固定效应模型	2.17（1.60，2.94）	<0.001
术前临床T分期	3^[14,17,18]	81.6	0.004	随机效应模型	1.19（0.52，2.74）	0.678