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
{"title":"Transcriptomic predictors of prostate cancer recurrence following focal cryotherapy: a pooled analysis of phase II trial and prospective cohort data","authors":"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","doi":"10.1016/j.jncc.2025.04.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 <em>vs</em> 0.38, <em>P</em> = 0.014) and remained significantly associated with recurrence after adjustment for GG (adjusted <em>OR</em>: 1.37 [95% CI: 1.01–1.93], <em>P</em> = 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% <em>vs</em> 0% [LD] <em>vs</em> 15.4% [basal-neuroendocrine] and 14.3% [basal-immune], <em>P</em> = 0.027). Higher expression of DNA repair pathway was also associated with recurrence (<em>OR</em>: 2.12 [95% CI: 1.09–4.57], <em>P</em> = 0.025).</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 5","pages":"Pages 515-523"},"PeriodicalIF":9.4000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the National Cancer Center","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667005425000444","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.