随着诊断手段的进步,越来越多的老年男性发现患有早期前列腺癌。由于一部分前列腺癌的发展类似于“乌龟”,因此随访观察也成为了早期前列腺癌的可选治疗方式。然而,目前判断惰性前列腺癌的标准主要依赖于穿刺报告的病理分析,均存在纳入侵袭性前列腺癌的风险。所以接受随访观察的患者,往往迫切地希望知道肿瘤恶化的风险。
随着诊断手段的进步,越来越多的老年男性发现患有早期前列腺癌。由于一部分前列腺癌的发展类似于“乌龟”,因此随访观察也成为了早期前列腺癌的可选治疗方式。然而,目前判断惰性前列腺癌的标准主要依赖于穿刺报告的病理分析,均存在纳入侵袭性前列腺癌的风险。所以接受随访观察的患者,往往迫切地希望知道肿瘤恶化的风险。
来自瑞士的研究组分析了171例接受随访观察的前列腺癌患者,中位随访时间为5年。结果显示28%的患者出现了疾病进展,进展的时间往往发生在确诊后28个月左右。分析疾病进展的原因可以看到:29%的患者是肿瘤体积增加,Gleason评分仍为6分;27%的患者出现主要Gleason评分4分以上的病变,其中17%进展为高危前列腺癌(Gleason评分至少为8分)。对于48例进展的患者,有3例在局部治疗后疾病仍然进一步恶化,需要进行内分泌治疗。整组病例的无病生存率为93%。
这项研究有两方面的重要意义:
首先,研究剖析了早期前列腺癌随访观察后的进展风险。5年之内有28%的随访观察患者出现疾病进展,大部分是因为Gleason评分的升高,并且有27%的患者出现4分以上的肿瘤,这种病变意味着前列腺癌从非致死性肿瘤转换为致死性肿瘤。因此,对于早期前列腺癌的患者,选择随访观察时,需要明确的告诉患者这两个数字——随访观察可能只是推迟了治疗的时间,也有可能错过治疗的最佳窗口。
其次,这项研究也揭示了随访观察需要改进的方向。随访观察的成功依赖于两项要素,首先是准确地判断患者为惰性前列腺癌,其次是推迟前列腺癌的治疗并不影响患者的长期生存率。
目前判断惰性前列腺癌的标准仍然依赖于病理特征,而同样入组标准的患者存在显著的预后差异——有的疾病停滞,有的手术后仍然复发进展。这种差异提示我们仍然缺乏描述前列腺癌生物学行为的准确指标,因此针对前列腺癌分子分型的研究对于选择随访观察的病例非常重要。
而推迟治疗和早期治疗的生存差异有多大,需要经过长期的随访才能得出。目前,局限性高危前列腺癌经过手术或放疗后的平均生存期超过8年。因此针对随访观察组的生存分析需要10年以上的长期数据才能得出。本项研究中整组病例的无病生存率为93%,并不能反映出等待观察治疗的全部信息。
朱耀 教授
肿瘤外科学博士,复旦大学附属肿瘤医院泌尿外科副主任医师,主攻前列腺癌的微创根治术和综合治疗,熟练开展保留性神经和尿控的前列腺癌根治术。入选2016年上海市青年科技启明星计划、第七届复旦大学十大医务青年和第三批复旦大学卓学人才计划,获得2015第一三共制药奖教金。近年来在国际一流学术刊物上以第一作者和通讯作者发表论文40余篇,其中15篇发表于美国泌尿外科学会官方杂志Journal of Urology和英国泌尿外科学会的官方杂志BJU International,研究成果被纳入欧美泌尿外科诊治指南和经典教科书。作为课题负责人承担国家自然科学基金两项,获批实用新型专利1项。曾受邀在美国MD Anderson癌症中心和日本金泽大学做专题学术报告,多次在欧美泌尿外科年会做会场发言交流。2012年作为项目第二完成人获得上海市科技进步奖一等奖、上海市医学科技奖一等奖和教育部高等学校科技进步奖二等奖。
研究摘要
953 Reclassified in active surveillance for prostate cancer: Was it worthwhile taking the risk?
Hefermehl L., Lehmann K.( Kantonsspital Baden, Dept. of Urology, Baden, Switzerland)
Introduction & Objectives: During Follow-Up (FU) a relevant number of patients under Active Surveillance (AS) will need definitive treatment due to reclassification. Was it worth while taking the risk of delayed intervention?
Material & Methods: We analyzed all consecutive patients, which were enrolled in our prospective AS program at our institution from 1999 to 2014. Inclusion criteria and FU schedule had to be adapted over time but met general recommendations. Reclassification was defined either as Gleason Score (GS) > 6 and/or increased tumor volume in the biopsy (>2 cores; >50% of core; bilateral), and lead to definitive treatment.
ResultsWe included 171 men with a median age of 66 years (61-69). Documented FU was a median of 60 months (range 36-90). Reclassification rate was 28% (48 men) and took place after a median FU of 28 months with a wide range of 21-61 months. For reclassified men disease free survival including AS as well as post-treatment time was 81 (49-109) months. Biopsy GS leading to reclassification were ≤6, 7 (3+4), 7 (4+3), 8, 9 and 10 in 14 (29%), 21 (44%), 5 (10.5%), 2 (4%), 5 (10.5%) and 1 (2%) men respectively. Hence, reclassification with dominant aggressive Gleason pattern (≥ 4+3) was found in 27% and high-risk cancer (GS ≥8) was found in 17% (8/48).
Definitive treatment was Radical Prostatectomy (RP), external beam radio therapy (RT) or primary Androgen Deprivation Therapy (ADT) in 32, 14, 1 and one patient has not yet decided. Out of this group three men had progressive disease and underwent ADT, one primarily after 26 months, two secondary after RT (41 & 116 months after inclusion and 104 & 24 months after RT). Men under AS only had uneventful FU for a median of 56 months (36-79). This stands in discrepancy to the anticipated median of 79 (57-121) months due to insufficient data, because many men do not keep to the FU plan. Kaplan Meier analysis revealed disease free survival for the total AS cohort of 93%.
Conclusions: Our 15 years experience in AS shows excellent long-term oncologic outcome despite a considerable reclassification rate of 28%. However, patients need to be informed that reclassification can take place even after many years of uneventful FU and that one sixth of reclassified men will show high-risk cancer.