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前列腺癌冷冻治疗的远期疗效及预测因素

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目的 探讨真实世界下前列腺冷冻消融术治疗前列腺癌的疗效及其预后因素.方法 回顾性分析2021年1月至2023年12月复旦大学附属肿瘤医院收治的105例前列腺癌患者的临床资料.根据患者远处转移情况分为无转移组62例(58.7%),转移组43例(41.3%).无转移组中位年龄79(73,82)岁,初诊前列腺特异性抗原(PSA)20(10,47)ng/ml,接受新辅助内分泌治疗37例(59.7%),术前PSA8(2,14)ng/ml;国际泌尿病理协会(ISUP)分级1级4例(6.5%),2级11例(17.7%),3 级 16 例(25.8%),4 级 16 例(25.8%),5 级 15 例(24.2%);T2期49 例,T3期 6 例,T4期 7例;N0期62例(100.0%),N1期0例.转移组中位年龄68(62,74)岁,初诊PSA 64(27,200)ng/ml,接受新辅助内分泌治疗42例(97.7%),术前PSA 0(0,3)ng/ml;ISUP分级1级0例,2级5例(11.6%),3 级3 例(7.0%),4 级 19 例(44.2%),5 级 16 例(37.2%);T2 期 29 例(67.4%),T3 期8 例(18.6%),T4期 6 例(14.0%);N0 期 38 例(88.4%),N,期5 例(11.6%);M1a 期5 例(11.6%),M1b期35例(81.4%),M1c期3例(7.0%).两组比较,T分期差异无统计学意义(P=0.346),其他指标差异均有统计学意义(P<0.05).前列腺癌冷冻消融术采用全麻或局部浸润麻醉,患者取截石位,留置F20三腔导尿管持续冲洗.在经直肠超声引导下,平行探头经会阴插入冷冻针,针尖距膀胱壁的安全距离为3 mm.采用全腺体冷冻模式,从患者腹侧开始向直肠侧逐层消融.采用超声实时观察冰球位置和范围,消融过程中调整冰球范围,使其与前列腺边缘贴合,同时保护周围结构.消融结束后,拔除冷冻针,碘伏消毒穿刺点后纱布压迫止血20 s至无出血后贴敷料.术后10 d拔除导尿管.术后第1天以及术后6、12周复查PSA.将术后第1天PSA与术前PSA比值定义为PSA释放率.术后生化复发定义为PSA较术后最低值升高超过0.2 ng/ml.比较两组的无PSA进展生存时间和并发症发生情况.结果 本研究所有手术均顺利完成.无转移组和转移组的PSA释放率分别为4.2(2.2,6.4)和3.9(1.5,6.7),差异无统计学意义(P=0.8272).术后 6 周中位 PSA 为 0.23(0.01,1.22)ng/ml,术后12周中位PSA为0.02(0.01,0.49)ng/ml.无转移组术后6周和12周中位PSA分别为0.42(0.25,1.00)ng/ml 和0.03(0.01,0.57)ng/ml.转移组术后 6 周和 12 周中位 PSA 分别为 0.30(0.14,0.50)ng/ml 和 0.02(0.01,1.17)ng/ml.中位随访时间 339(128,571)d.术后均未发生 Clavien-Dindo≥2级并发症.1例(0.9%)术后1个月出现膀胱颈口尿道狭窄,行经尿道前列腺切除术后好转;2例(1.9%)术后7 d出现尿潴留,再次留置尿管2周后恢复正常.无尿失禁患者.2例(1.9%)非肿瘤性死亡,1例死于心脏病,1例死于新型冠状病毒肺炎合并症.随访期间29例(27.6%)发生PSA进展,中位无PSA进展时间为808.0 d.无转移组中位无PSA进展生存时间未达到,转移组中位无PSA进展时间为764.0 d,两组差异无统计学意义(P=0.422).单因素分析结果显示,术前 PSA(HR=1.02,95%CI 1.00~1.03,P=0.048),T3 期(HR=9.00,95%CI 2.59~31.25,P<0.01),T4 期(HR=5.83,95%CI 1.68~20.21,P=0.005)是无 PSA 进展的预后预测因素.多因素分析结果显示,T3期(HR=9.08,95%CI2.47~33.45,P<0.01)、T4 期(HR=4.50,95%CI 1.18~17.22,P=0.028)是无PSA进展的独立预后预测因素.结论 前列腺癌冷冻治疗的安全性较高.无论是否有远处转移,对于初诊时T分期<T3期的前列腺癌患者前列腺冷冻消融术的疗效更好.
Long-term prognostic predictors of prostate cancer patients who underwent cryotherapy
Objective To explore the efficient prognostic factors of cryotherapy for prostate cancer in the real-world setting.Methods The clinical data of 105 prostate cancer patients treated at the Fudan University Shanghai Cancer center from January 2021 to December 2023 were analyzed retrospectively.The patients were divided into a non-metastatic group(62 cases,58.7%)and a metastatic group(43 cases,41.3%)based on the presence or absence of distant metastasis.In the non-metastatic group,the median age was 79 years(range 73 to 82),the initial PSA was 20 ng/ml(range 10 to 47),37 cases(59.7%)received neoadjuvant endocrine therapy,and the preoperative PSA was 8 ng/ml(range 2 to 14).The ISUP grades were Grade 1 in 4 cases(6.5%),Grade 2 in 11 cases(17.7%),Grade 3 in 16 cases(25.8%),Grade 4 in 16 cases(25.8%),and Grade 5 in 15 cases(24.2%).The T-stages were T2 in 49 cases,T3 in 6 cases,and T4 in 7 cases.All cases were N0.In the metastatic group,the median age was 68 years(range 62 to 74),the initial PSA was 64 ng/ml(range 27 to 200),42 cases(97.7%)received neoadjuvant endocrine therapy,and the preoperative PSA was 0 ng/ml(range 0 to 3).The ISUP grades were Grade 1 in 0 cases,Grade 2 in 5 cases(11.6%),Grade 3 in 3 cases(7.0%),Grade 4 in 19 cases(44.2%),and Grade 5 in 16 cases(37.2%).The T-stages were T2 in 29 cases(67.4%),T3 in 8 cases(18.6%),and T4 in 6 cases(14.0%).The N-stages were N0 in 38 cases(88.4%)and N,in 5 cases(11.6%).The M-stages were M1a in 5 cases(11.6%),M1b in 35 cases(81.4%),and M1c in 3 cases(7.0%).The difference in T-stage between the two groups was not statistically significant(P=0.346),while differences in other indicators were statistically significant(P<0.05).The cryotherapy for prostate cancer was performed under general or local anesthesia,with the patients in the lithotomy position and a F20 three-lumen catheter was placed for continuous irrigation.Under transrectal ultrasound guidance,the cryoprobes were inserted parallel to the probe through the perineum,with a safe distance of 3 mm from the bladder wall.A whole-gland freezing mode was adopted,starting from the ventral side and freezing layer by layer towards the rectal side.Ultrasound was used in real-time to observe the ice ball's position and extent,adjusting it during ablation to conform to the prostate's margins while protecting surrounding structures.After ablation,the cryoprobes were removed,the puncture sites were disinfected with povidone-iodine,and gauze was applied for 20 seconds to achieve hemostasis before applying dressings.The catheter was removed 10 days postoperatively.PSA levels were rechecked on the first postoperative day and at 6 and 12 weeks postoperatively.The ratio of PSA on the first postoperative day to preoperative PSA was defined as the PSA release rate.Biochemical recurrence was defined as a PSA increase of more than 0.2 ng/ml above the postoperative nadir.The PSA progression-free survival time and the incidence of complications were compared between the two groups.Results All procedures were successfully completed.The PSA release rates for the non-metastatic and metastatic groups were 4.2(2.2,6.4)and 3.9(1.5,6.7),respectively,with no statistical significant difference(P=0.8272).The median PSA at 6 weeks postoperatively was 0.23(0.01,1.22)ng/ml,and at 12 weeks it was 0.02(0.01,0.49)ng/ml.The median PSA for the non-metastatic group was 0.42(0.25,1.00)ng/ml at 6 weeks,and it was 0.03(0.01,0.57)ng/ml at 12 weeks.For the metastatic group,the median PSA was 0.30(0.14,0.50)ng/ml at 6 weeks,and it was 0.02(0.01,1.17)ng/ml at 12 weeks.The median follow-up period was 339 days(range 128 to 571).No Clavien-Dindo grade ≥ 2 complications occurred postoperatively.One case(0.9%)experienced bladder neck stricture one month postoperatively,which improved by transurethral resection of the prostate(TURP).Two cases(1.9%)experienced urinary retention seven days postoperatively,which resolved after re-catheterization for two weeks.No urinary incontinence was reported.Two non-tumor-related deaths occurred(1.9%),one due to cardiac disease and the other due to complications from COVID-19.During follow-up,29 cases(27.6%)experienced PSA progression,with a median PSA progression-free survival time of 808.0 days.The median PSA progression-free survival time was not reached in the non-metastatic group,while it was 764.0 days in the metastatic group.There was no statistical significant difference in PSA progression-free survival between the two groups(P=0.422).Univariate analysis showed that preoperative PSA(HR=1.02,95%CI 1.00-1.03,P=0.048),T3 stage(HR=9.00,95%CI 2.59-31.25,P<0.01),and T4 stage(HR=5.83,95%CI 1.68-20.21,P=0.005)were prognostic factors for PSA progression-free survival.Multivariate analysis showed that T3 stage(HR=9.08,95%CI 2.47-33.45,P<0.01)and T4 stage(HR=4.50,95%CI 1.18-17.22,P=0.028)were independent prognostic factors for PSA progression-free survival.Conclusions Cryotherapy for prostate cancer has a high safety profile.The efficacy of Cryotherapy is better in patients with T-stage<T3 at initial diagnosis,regardless of the presence of distant metastasis.

Prostate cancerCryotherapyPrognosisReal-world

万方宁、戴波、叶碧然、林国文、叶定伟

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复旦大学附属肿瘤医院泌尿外科 复旦大学上海医学院肿瘤学系上海市泌尿肿瘤研究所,上海 200032

前列腺癌 冷冻消融 预后 真实世界

2024

中华泌尿外科杂志
中华医学会

中华泌尿外科杂志

CSTPCD北大核心
影响因子:1.628
ISSN:1000-6702
年,卷(期):2024.45(6)