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 i...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.展开更多
Dear editor,Prostate cancer(PCa)remains a major healthcare burden in men globally[1].Most patients present with localized disease,and treatment is recommended based on risk classification systems like the National Com...Dear editor,Prostate cancer(PCa)remains a major healthcare burden in men globally[1].Most patients present with localized disease,and treatment is recommended based on risk classification systems like the National Comprehensive Cancer Network(NCCN)[2].However,these methods are imprecise for estimating metastasis-free survival and prostate cancer-specific mortality and thus biomarkers that can predict tumor aggression are needed[3–5].Several studies have since characterized the molecular landscape of localized PCa in White[4,5]and Black/African-American men[6],but data is lacking in Asian men.The Chinese Prostate Cancer Genome and Epigenome Atlas(CPGEA)reported on the genomic and epigenomic landscape of 208 PCa of men from China[7].Comparative analyses between the CPGEA cohort and data from The Cancer Genome Atlas(TCGA)revealed higher frequencies of Forkhead box A1(FOXA1)and chromodomain-helicase DNA-binding 1(CHD1)mutations,and lower frequencies of phosphatase and tensin homolog(PTEN)mutations and transmembrane protease serine 2-E26 transformationspecific related gene(TMPRSS2-ERG)fusion in Chinese compared with White men[7].These preliminary findings highlight the presence of race-specific differences in molecular phenotypes of PCa.展开更多
基金supported by National Medical Research Council Sin‐gapore,National Medical Research Council Singapore(grant numbers:TA20nov-0011,NMRC/CSA‐INV/0027/2018,CSAINV20nov‐0021)Duke‐NUS Oncology Academic Program+2 种基金Goh Foundation Proton Research ProgramNCCS Cancer FundKua Hong Pak Head and Neck Cancer Research Program.
文摘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.
基金National Medical Research Council Singapore Clinician Scientist Award Duke-NUS Oncology Academic Program Goh Foundation Proton Research Programme NCCS Cancer Fund Kua Hong Pak Head and Neck Cancer Research Programme。
文摘Dear editor,Prostate cancer(PCa)remains a major healthcare burden in men globally[1].Most patients present with localized disease,and treatment is recommended based on risk classification systems like the National Comprehensive Cancer Network(NCCN)[2].However,these methods are imprecise for estimating metastasis-free survival and prostate cancer-specific mortality and thus biomarkers that can predict tumor aggression are needed[3–5].Several studies have since characterized the molecular landscape of localized PCa in White[4,5]and Black/African-American men[6],but data is lacking in Asian men.The Chinese Prostate Cancer Genome and Epigenome Atlas(CPGEA)reported on the genomic and epigenomic landscape of 208 PCa of men from China[7].Comparative analyses between the CPGEA cohort and data from The Cancer Genome Atlas(TCGA)revealed higher frequencies of Forkhead box A1(FOXA1)and chromodomain-helicase DNA-binding 1(CHD1)mutations,and lower frequencies of phosphatase and tensin homolog(PTEN)mutations and transmembrane protease serine 2-E26 transformationspecific related gene(TMPRSS2-ERG)fusion in Chinese compared with White men[7].These preliminary findings highlight the presence of race-specific differences in molecular phenotypes of PCa.
