Abstract
Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H&E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy samples to the Australian Prostate Cancer Bioresource between 2006 and 2014. The prediction of CR was the primary outcome (median time to CR 79.8 months), and BCR was assessed as a secondary outcome (median time to BCR 41.7 months). The associations of (1) H&E ISUP grade groups and (2) modified ISUP grade groups informed by the Appl1, Sortilin and Syndecan-1 immunohistochemistry (IHC) labelling were modelled with BCR and CR using Cox proportional hazard approaches. IHC-assisted grading was more predictive than H&E for BCR (C-statistic 0.63 vs. 0.59) and CR (C-statistic 0.71 vs. 0.66). On adjusted analysis, IHC-assisted ISUP grading was independently associated with both outcome measures. IHC-assisted ISUP grading using the biomarker panel was an independent predictor of individual BCR and CR. Prospective studies are needed to further validate this biomarker technology and to define BCR and CR associations in real-world cohorts.
| Original language | English |
|---|---|
| Article number | 3215 |
| Journal | Cancers |
| Volume | 15 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published or Issued - Jun 2023 |
Keywords
- biomarkers
- clinical recurrence
- diagnosis
- prognosis
- prostate cancer
ASJC Scopus subject areas
- Oncology
- Cancer Research
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}
In: Cancers, Vol. 15, No. 12, 3215, 06.2023.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Prediction of Prostate Cancer Biochemical and Clinical Recurrence Is Improved by IHC-Assisted Grading Using Appl1, Sortilin and Syndecan-1
AU - Logan, Jessica M.
AU - Hopkins, Ashley M.
AU - Martini, Carmela
AU - Sorvina, Alexandra
AU - Tewari, Prerna
AU - Prabhakaran, Sarita
AU - Huzzell, Chelsea
AU - Johnson, Ian R.D.
AU - Hickey, Shane M.
AU - Ung, Ben S.Y.
AU - Lazniewska, Joanna
AU - Brooks, Robert D.
AU - Moore, Courtney R.
AU - Caruso, Maria C.
AU - Karageorgos, Litsa
AU - Martin, Cara M.
AU - O’Toole, Sharon
AU - Bogue Edgerton, Laura
AU - Ward, Mark P.
AU - Bates, Mark
AU - Selemidis, Stavros
AU - Esterman, Adrian
AU - Heffernan, Sheena
AU - Keegan, Helen
AU - Ní Mhaolcatha, Sarah
AU - O’Connor, Roisin
AU - Malone, Victoria
AU - Carter, Marguerite
AU - Ryan, Katie
AU - Clarke, Andres
AU - Brady, Nathan
AU - Klebe, Sonja
AU - Samaratunga, Hemamali
AU - Delahunt, Brett
AU - Sorich, Michael J.
AU - Moretti, Kim
AU - Butler, Lisa M.
AU - O’Leary, John J.
AU - Brooks, Douglas A.
N1 - Funding Information: Funding for this project was provided by Envision Sciences Pty Ltd., the University of South Australia, a Cancer Council SA Beat Cancer Grant, the Movember Foundation/Prostate Cancer Foundation of Australia’s Research Program and the Australian Federal Government (NHMRC development grant GNT1092904 and MTP Connect Biomedical Translation Bridge Program grant BTBR200074). L.M.B. was supported by a Beat Cancer SA Beat Cancer Project Principal Cancer Research Fellowship (PRF1117). A.M.H is supported by an Emerging Leader Investigator Grant from the National Health and Medical Research Council, Australia (APP2008119). Funding Information: Funding for this project was provided by Envision Sciences Pty Ltd., the University of South Australia, a Cancer Council SA Beat Cancer Grant, the Movember Foundation/Prostate Cancer Foundation of Australia’s Research Program and the Australian Federal Government (NHMRC development grant GNT1092904 and MTP Connect Biomedical Translation Bridge Program grant BTBR200074). L.B. was supported by a Beat Cancer SA Beat Cancer Project Principal Cancer Research Fellowship (PRF1117). A.M.H is supported by an Emerging Leader Investigator Grant from the National Health and Medical Research Council, Australia (APP2008119). D.A.B. is from the University of South Australia, I.R.D.J. is also from the University of South Australia and L.M.B. is from the University of Adelaide and hold patent WO2014197937A1 ‘Methods for Detecting Prostate Cancer’, which involves this manuscript (Original Patent). The Original Patent holders have appointed UniSA Ventures Pty Ltd., the wholly-owned commercialisation arm of the University of South Australia, to manage the commercialisation of the Original Patent. UniSA Ventures Pty Ltd. Has entered into arm’s-length arrangements with Envision Sciences Pty Ltd., under which UniSA Ventures will receive financial benefits from the successful commercialisation of the Original Patent. Envision Sciences Pty Ltd. is a privately-owned Australian company that is commercialising its work in the field of cancer diagnostics and holds additional patents, including PCT/AU2020/050925 “Methods for Confirming Detection and Evaluating the Progression of a Prostate Cancer” involving the invention reported in this manuscript and is using this with the Original Patent under licence. Envision Sciences Pty Ltd. Has engaged the University of South Australia on arm’s-length terms to conduct research and development work, including the subject matter in this manuscript. D.A.B. is a professor and leader of the Mechanisms in Cell Biology and Disease Research Group in Clinical and Health Sciences at the University of South Australia. D.A.B. is a founding shareholder and benefits from Envision Sciences Pty Ltd.’s research funding. J.J.O. is a shareholder and benefits from Envision Sciences Pty Ltd.’s research funding. D.A.B., L.K., J.M.L.,C.M, A.E., A.S., B.S.-Y.U. and S.P. are employees of the University of South Australia, L.M.B. is an employee of Adelaide University and J.J.O. is an employee of Trinity College Dublin, and each receive benefit from the funding provided by Envision Sciences Pty Ltd., the University of South Australia and the Australian Federal Government for their research work. Funding Information: D.A.B., L.K., J.M.L., C.M., A.E., A.S., B.S.-Y.U. and S.P. are employees of the University of South Australia, L.M.B. is an employee of Adelaide University and J.J.O. is an employee of Trinity College Dublin, and each receive benefit from the funding provided by Envision Sciences Pty Ltd., the University of South Australia and the Australian Federal Government for their research work. Funding Information: Funding for this project was provided by Envision Sciences Pty Ltd., the University of South Australia, a Cancer Council SA Beat Cancer Grant, the Movember Foundation/Prostate Cancer Foundation of Australia’s Research Program and the Australian Federal Government (NHMRC development grant GNT1092904 and MTP Connect Biomedical Translation Bridge Program grant BTBR200074). L.B. was supported by a Beat Cancer SA Beat Cancer Project Principal Cancer Research Fellowship (PRF1117). A.M.H is supported by an Emerging Leader Investigator Grant from the National Health and Medical Research Council, Australia (APP2008119). D.A.B. is from the University of South Australia, I.R.D.J. is also from the University of South Australia and L.M.B. is from the University of Adelaide and hold patent WO2014197937A1 ‘Methods for Detecting Prostate Cancer’, which involves this manuscript (Original Patent). The Original Patent holders have appointed UniSA Ventures Pty Ltd., the wholly-owned commercialisation arm of the University of South Australia, to manage the commercialisation of the Original Patent. UniSA Ventures Pty Ltd. has entered into arm’s-length arrangements with Envision Sciences Pty Ltd., under which UniSA Ventures will receive financial benefits from the successful commercialisation of the Original Patent. Envision Sciences Pty Ltd. is a privately-owned Australian company that is commercialising its work in the field of cancer diagnostics and holds additional patents, including PCT/AU2020/050925 “Methods for Confirming Detection and Evaluating the Progression of a Prostate Cancer” involving the invention reported in this manuscript and is using this with the Original Patent under licence. Envision Sciences Pty Ltd. has engaged the University of South Australia on arm’s-length terms to conduct research and development work, including the subject matter in this manuscript. D.A.B. is a professor and leader of the Mechanisms in Cell Biology and Disease Research Group in Clinical and Health Sciences at the University of South Australia. D.A.B. is a founding shareholder and benefits from Envision Sciences Pty Ltd.’s research funding. J.J.O. is a shareholder and benefits from Envision Sciences Pty Ltd.’s research funding. D.A.B., L.K., J.M.L., C.M., A.E., A.S., B.S.-Y.U. and S.P. are employees of the University of South Australia, L.M.B. is an employee of Adelaide University and J.J.O. is an employee of Trinity College Dublin, and each receive benefit from the funding provided by Envision Sciences Pty Ltd., the University of South Australia and the Australian Federal Government for their research work. Publisher Copyright: © 2023 by the authors.
PY - 2023/6
Y1 - 2023/6
N2 - Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H&E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy samples to the Australian Prostate Cancer Bioresource between 2006 and 2014. The prediction of CR was the primary outcome (median time to CR 79.8 months), and BCR was assessed as a secondary outcome (median time to BCR 41.7 months). The associations of (1) H&E ISUP grade groups and (2) modified ISUP grade groups informed by the Appl1, Sortilin and Syndecan-1 immunohistochemistry (IHC) labelling were modelled with BCR and CR using Cox proportional hazard approaches. IHC-assisted grading was more predictive than H&E for BCR (C-statistic 0.63 vs. 0.59) and CR (C-statistic 0.71 vs. 0.66). On adjusted analysis, IHC-assisted ISUP grading was independently associated with both outcome measures. IHC-assisted ISUP grading using the biomarker panel was an independent predictor of individual BCR and CR. Prospective studies are needed to further validate this biomarker technology and to define BCR and CR associations in real-world cohorts.
AB - Gleason scoring is used within a five-tier risk stratification system to guide therapeutic decisions for patients with prostate cancer. This study aimed to compare the predictive performance of routine H&E or biomarker-assisted ISUP (International Society of Urological Pathology) grade grouping for assessing the risk of biochemical recurrence (BCR) and clinical recurrence (CR) in patients with prostate cancer. This retrospective study was an assessment of 114 men with prostate cancer who provided radical prostatectomy samples to the Australian Prostate Cancer Bioresource between 2006 and 2014. The prediction of CR was the primary outcome (median time to CR 79.8 months), and BCR was assessed as a secondary outcome (median time to BCR 41.7 months). The associations of (1) H&E ISUP grade groups and (2) modified ISUP grade groups informed by the Appl1, Sortilin and Syndecan-1 immunohistochemistry (IHC) labelling were modelled with BCR and CR using Cox proportional hazard approaches. IHC-assisted grading was more predictive than H&E for BCR (C-statistic 0.63 vs. 0.59) and CR (C-statistic 0.71 vs. 0.66). On adjusted analysis, IHC-assisted ISUP grading was independently associated with both outcome measures. IHC-assisted ISUP grading using the biomarker panel was an independent predictor of individual BCR and CR. Prospective studies are needed to further validate this biomarker technology and to define BCR and CR associations in real-world cohorts.
KW - biomarkers
KW - clinical recurrence
KW - diagnosis
KW - prognosis
KW - prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=85163809871&partnerID=8YFLogxK
U2 - 10.3390/cancers15123215
DO - 10.3390/cancers15123215
M3 - Article
AN - SCOPUS:85163809871
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 12
M1 - 3215
ER -