Determining the impact of spatial heterogeneity on genomic prognostic biomarkers for localized prostate cancer
AuthorsBrastianos, H. C.
Chua, M. L. K.
Fleshner, N. E.
van der Kwast, T.
Bristow, Robert G
Boutros, P. C.
AffiliationRadiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
MetadataShow full item record
AbstractLocalized prostate tumors show remarkably diverse clinical courses, with some being cured by local therapy alone, while others rapidly relapse and have a lethal course despite precision surgery or radiotherapy. Many genomic biomarkers have been developed to predict this clinical behavior, but these are confounded by the extreme spatial heterogeneity of prostate tumors: most are multifocal and harbor multiple subclonal populations. To quantify the influence of spatial heterogeneity on genomic prognostic biomarkers, we developed a case-control high-risk cohort (n = 42) using a prospective registry, risk matched by clinicopathologic prognostic indices. Half of the cohort had early biochemical recurrence (BCR; ie, ?18 mo), while half remained without evidence of disease for at least 48 mo after radical prostatectomy. We then genomically profiled multiple tumor foci per patient, analyzing 119 total specimens. These data allowed us to validate three published genomic prognostic biomarkers and quantify their sensitivity to tumor spatial heterogeneity. Remarkably, all three biomarkers robustly predicted early BCR, and all three were robust to spatiogenomic variability. These data suggest that DNA-based genomic biomarkers can overcome intratumoral heterogeneity: single biopsies may be sufficient to estimate the risk of early BCR after radical treatment in patients with high-risk disease. PATIENT SUMMARY: We investigated whether heterogeneity between tumor regions within the prostate affects the accuracy of DNA-based biomarkers predicting early relapse after prostatectomy. We observed persistent accuracy in predicting disease relapse, suggesting that spatial heterogeneity may not hinder biomarker performance. Keywords: Biomarkers; Genomics; Heterogeneity; Prognostication; Prostate cancer.
CitationBrastianos HC, Murgic J, Salcedo A, Chua MLK, Meng A, Fraser M, et al. Determining the Impact of Spatial Heterogeneity on Genomic Prognostic Biomarkers for Localized Prostate Cancer. Eur Urol Oncol. 2020.
JournalEuropean Urology Oncology
- Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study.
- Authors: Lalonde E, Ishkanian AS, Sykes J, Fraser M, Ross-Adams H, Erho N, Dunning MJ, Halim S, Lamb AD, Moon NC, Zafarana G, Warren AY, Meng X, Thoms J, Grzadkowski MR, Berlin A, Have CL, Ramnarine VR, Yao CQ, Malloff CA, Lam LL, Xie H, Harding NJ, Mak DYF, Chu KC, Chong LC, Sendorek DH, P'ng C, Collins CC, Squire JA, Jurisica I, Cooper C, Eeles R, Pintilie M, Dal Pra A, Davicioni E, Lam WL, Milosevic M, Neal DE, van der Kwast T, Boutros PC, Bristow RG
- Issue date: 2014 Dec
- Translating a Prognostic DNA Genomic Classifier into the Clinic: Retrospective Validation in 563 Localized Prostate Tumors.
- Authors: Lalonde E, Alkallas R, Chua MLK, Fraser M, Haider S, Meng A, Zheng J, Yao CQ, Picard V, Orain M, Hovington H, Murgic J, Berlin A, Lacombe L, Bergeron A, Fradet Y, Têtu B, Lindberg J, Egevad L, Grönberg H, Ross-Adams H, Lamb AD, Halim S, Dunning MJ, Neal DE, Pintilie M, van der Kwast T, Bristow RG, Boutros PC
- Issue date: 2017 Jul
- A Biopsy-based 17-gene Genomic Prostate Score Predicts Recurrence After Radical Prostatectomy and Adverse Surgical Pathology in a Racially Diverse Population of Men with Clinically Low- and Intermediate-risk Prostate Cancer.
- Authors: Cullen J, Rosner IL, Brand TC, Zhang N, Tsiatis AC, Moncur J, Ali A, Chen Y, Knezevic D, Maddala T, Lawrence HJ, Febbo PG, Srivastava S, Sesterhenn IA, McLeod DG
- Issue date: 2015 Jul
- Intratumoral and Intertumoral Genomic Heterogeneity of Multifocal Localized Prostate Cancer Impacts Molecular Classifications and Genomic Prognosticators.
- Authors: Wei L, Wang J, Lampert E, Schlanger S, DePriest AD, Hu Q, Gomez EC, Murakam M, Glenn ST, Conroy J, Morrison C, Azabdaftari G, Mohler JL, Liu S, Heemers HV
- Issue date: 2017 Feb
- Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy.
- Authors: Spratt DE, Dai DLY, Den RB, Troncoso P, Yousefi K, Ross AE, Schaeffer EM, Haddad Z, Davicioni E, Mehra R, Morgan TM, Rayford W, Abdollah F, Trabulsi E, Achim M, Tapia ELN, Guerrero M, Karnes RJ, Dicker AP, Hurwitz MA, Nguyen PL, Feng FFY, Freedland SJ, Davis JW
- Issue date: 2018 Jul