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dc.contributor.authorRamotar, M.
dc.contributor.authorChua, M. L. K.
dc.contributor.authorTruong, H.
dc.contributor.authorHosni, A.
dc.contributor.authorPintilie, M.
dc.contributor.authorDavicioni, E.
dc.contributor.authorFleshner, N. E.
dc.contributor.authorDicker, A. P.
dc.contributor.authorBristow, Robert G
dc.contributor.authorHe, H. H.
dc.contributor.authorvan der Kwast, T.
dc.contributor.authorDen, R. B.
dc.contributor.authorBerlin, A.
dc.date.accessioned2021-09-30T11:56:15Z
dc.date.available2021-09-30T11:56:15Z
dc.date.issued2021en
dc.identifier.citationRamotar M, Chua MLK, Truong H, Hosni A, Pintilie M, Davicioni E, et al. Subpathologies and genomic classifier for treatment individualization of post-prostatectomy radiotherapy. Urologic Oncology: Seminars and Original Investigations. 2021 Sep.en
dc.identifier.pmid34538726en
dc.identifier.doi10.1016/j.urolonc.2021.08.013en
dc.identifier.urihttp://hdl.handle.net/10541/624650
dc.description.abstractPurpose/objective: Risk-stratification for post-prostatectomy radiotherapy (PORT) using conventional clinicopathologic indexes leads to substantial over- and under-treatment. Better patient selection could spare unnecessary toxicities and improve outcomes. We investigated the prognostic utility of unfavorable subpathologies intraductal carcinoma and cribriform architecture (IDC/CA), and a 22-gene Decipher genomic classifier (GC) in prostate cancer (PCa) patients receiving PORT. Material/methods: A cohort of 302 men who received PORT at 2 academic institutions was pooled. PORT was predominately delivered as salvage (62% of cases); 20% received HT+PORT. Specimens were centrally reviewed for IDC/CA presence. In 104 cases, GC scores were determined. Endpoints were biochemical relapse-free (bRFR) and metastasis-free (mFR) rates. Results: After a median follow-up of 6.49-years, 135 (45%) and 40 (13%) men experienced biochemical relapse and metastasis, respectively. IDC/CA were identified in 160 (53%) of cases. Men harboring IDC/CA experienced inferior bRFR (HR 2.6, 95%CI 1.8-3.2, P<0.001) and mFR (HR 3.1, 95%CI 1.5-6.4, P = 0.0014). Patients with GC scores, 22 (21%) were stratified low-, 30 (29%) intermediate-, and 52 (50%) high-risk. GC low-risk was associated with superior bRFR (HR 0.25, 95%CI 0.1-0.5, P<0.001) and mFR (HR 0.15, 95%CI 0.03-0.8, P = 0.025). On multivariable analyses, IDC/CA and GC independently predicted for bRFR, corresponding to improved discrimination (C-index = 0.737 (95%CI 0.662-0.813)). Conclusions: IDC/CA subpathologies and GC predict for biochemical relapse and metastasis beyond conventional clinicopathologic indexes in the PORT setting. Patients harboring IDC/CA are at higher risk of relapse after maximal local therapies, thus warranting consideration for treatment intensification strategies. Conversely, for men with absence of IDC/CA and low GC scores, de-intensification strategies could be explored.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1016/j.urolonc.2021.08.013en
dc.titleSubpathologies and genomic classifier for treatment individualization of post-prostatectomy radiotherapyen
dc.typeArticleen
dc.contributor.departmentDepartment of Radiation Oncology, University of Toronto; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canadaen
dc.identifier.journalUrologic Oncologyen
dc.description.noteen]


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