前列腺癌局部冷冻治疗后复发的转录组学预测因素:II期试验和前瞻性队列数据的汇总分析

IF 9.4 Q1 ONCOLOGY
Kae Jack Tay , Boon Hao Hong , Enya Hui Wen Ong , Kah Min Tan , Gianella Cabuhat Pacho , Samantha Jingxuan Wong , Yu Guang Tan , Yan Mee Law , Nye Thane Ngo , Puay Hoon Tan , John S.P. Yuen , Henry S.S. Ho , Kenneth Chen , Jiping Peng , Clare Wei Tian Foo , Xin Xiu Sam , Jeffrey K.L. Tuan , Ravindran Kanesvaran , Rajan T. Gupta , Steven Rozen , Melvin Lee Kiang Chua
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引用次数: 0

摘要

目的局灶治疗(FT)是有限体积临床显著性前列腺癌(csPCa)的一种潜在治疗选择。然而,尽管经过严格的筛选,仍有大约20%的患者出现早期治疗失败。我们研究了转录组谱与ft后csPCa复发的关系。方法52名来自II期试验(NCT04138914)和前瞻性观察队列的男性接受了csPCa的局灶冷冻治疗。患者接受了多参数磁共振成像,并在ft术前和术后1年进行了靶向和全身饱和活检。复发定义为癌级组(GG)≥2在ft活检后1年。使用Decipher基因组分类器(GC)对治疗前病变进行分析。GC评分、光基础状态、肿瘤微环境和肿瘤标志通路与csPCa复发相关。结果中位PSA为7.0 ng/dl;37/52(71.1%)男性GG2、12/52 (23.1%)GG3、3/52 (5.8%)GG4癌。9/52(17.3%)男性复发。复发患者的中位GC评分较高(0.60 vs 0.38, P = 0.014),校正GG后仍与复发显著相关(校正OR: 1.37 [95% CI: 1.01-1.93], P = 0.04)。基于前列腺癌特异性亚型分类(PSC)的发光增殖性肿瘤比发光分化(LD)和基础亚型有更多的csPCa复发率(30.4% vs 0% [LD] vs 15.4%[基础神经内分泌]和14.3%[基础免疫],P = 0.027)。DNA修复通路的高表达也与复发相关(OR: 2.12 [95% CI: 1.09-4.57], P = 0.025)。结论GC评分越高,术后csPCa复发风险越大。GC低风险和PSC-LD csPCa患者可能是FT的理想亚组。需要在大队列中进行前瞻性验证。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transcriptomic predictors of prostate cancer recurrence following focal cryotherapy: a pooled analysis of phase II trial and prospective cohort data

Objective

Focal therapy (FT) is a potential treatment option for limited-volume clinically-significant prostate cancer (csPCa). However, despite rigorous selection, approximately 20% of patients experience early failure. We investigated the association of transcriptomic profiles and csPCa recurrence post-FT.

Methods

52 men from a phase II trial (NCT04138914) and a prospective observational cohort underwent focal cryotherapy for csPCa. Patients underwent multiparametric magnetic resonance imaging, and targeted and systematic-saturation biopsy before- and 1-year post-FT. Recurrence was defined as grade-group (GG) ≥2 cancer in the 1-year post-FT biopsy. Pre-treatment lesions were profiled using the Decipher genomic classifier (GC). GC scores, luminal-basal status, tumor microenvironment and cancer hallmark pathways were correlated with csPCa recurrence.

Results

Median PSA was 7.0 ng/dl; 37/52 (71.1%) men had GG2, 12/52 (23.1%) GG3, and 3/52 (5.8%) GG4 cancer. Recurrence was observed in 9/52 (17.3%) men. Median GC score was higher in patients with recurrence (0.60 vs 0.38, P = 0.014) and remained significantly associated with recurrence after adjustment for GG (adjusted OR: 1.37 [95% CI: 1.01–1.93], P = 0.04). Luminal-proliferative tumors based on the prostate cancer-specific subtyping classifier (PSC) had more csPCa recurrence compared with luminal-differentiated (LD) and basal subtypes (30.4% vs 0% [LD] vs 15.4% [basal-neuroendocrine] and 14.3% [basal-immune], P = 0.027). Higher expression of DNA repair pathway was also associated with recurrence (OR: 2.12 [95% CI: 1.09–4.57], P = 0.025).

Conclusions

Higher GC score is associated with risk of csPCa recurrence post-FT. Patients with GC low-risk and PSC-LD csPCa may represent the ideal subgroup for FT. Prospective validation in a large cohort is warranted.
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