Baseline circulating tumor cell count as a prognostic marker of PSA response and disease progression in metastatic castrate-sensitive prostate cancer (SWOG S1216)

Amir Goldkorn; Catherine Tangen; Melissa Plets; Gareth J. Morrison; Alexander Cunha; Tong Xu; Jacek K. Pinski; Sue A. Ingles; Timothy Triche; Andrea L. Harzstark; Manish Kohli; Gary R. MacVicar; Daniel A. Vaena; Anthony W. Crispino; David J. McConkey; Primo N. Lara; Maha H.A. Hussain; David I. Quinn; Nicholas J. Vogelzang; Ian Murchie Thompson; Neeraj Agarwal

doi:10.1158/1078-0432.CCR-20-3587

Baseline circulating tumor cell count as a prognostic marker of PSA response and disease progression in metastatic castrate-sensitive prostate cancer (SWOG S1216)

Amir Goldkorn^*, Catherine Tangen, Melissa Plets, Gareth J. Morrison, Alexander Cunha, Tong Xu, Jacek K. Pinski, Sue A. Ingles, Timothy Triche, Andrea L. Harzstark, Manish Kohli, Gary R. MacVicar, Daniel A. Vaena, Anthony W. Crispino, David J. McConkey, Primo N. Lara, Maha H.A. Hussain, David I. Quinn, Nicholas J. Vogelzang, Ian Murchie ThompsonNeeraj Agarwal

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Purpose: In metastatic castrate-sensitive prostate cancer (mCSPC), combined androgen axis inhibition is a standard of care. Noninvasive biomarkers that guide initial therapy decisions are needed. We hypothesized that CellSearch circulating tumor cell (CTC) count, an FDA-cleared assay in metastatic castrate-resistant prostate cancer (mCRPC), is a relevant biomarker in mCSPC. Experimental Design: SWOG S1216 is a phase III prospective randomized trial of androgen deprivation therapy (ADT) combined with orteronel or bicalutamide for mCSPC. CellSearch CTC count was measured at registration (baseline). Prespecified CTC cut-off points of 0, 1-4, and ≥5 were correlated with baseline patient characteristics and, in a stratified subsample, were also correlated with two prespecified trial secondary endpoints: 7-month PSA ≤0.2 ng/mL versus 0.2-4.0 versus >4.0 (intermediate endpoint for overall survival); and progressionfree survival (PFS) ≤ versus >2 years. Results: A total of 523 patients submitted baseline samples, and CTCs were detected (median 3) in 33%. Adjusting for two trial stratification factors (disease burden and timing of ADT initiation), men with undetectable CTCs had nearly nine times the odds of attaining 7-month PSA ≤ 0.2 versus > 4.0 [OR 8.8, 95% confidence interval (CI), 2.7-28.6, P < 0.001, N = 264] and four times the odds of achieving > 2 years PFS (OR 4.0, 95% CI, 1.9-8.5, P < 0.001, N = 336) compared with men with baseline CTCs ≥5. Conclusions: Baseline CT Ccount in mCSPC is highly prognostic of 7-month PSA and 2-year PFS after adjusting for disease burden and discriminates men who are likely to experience poor survival outcomes.

Original language	English (US)
Pages (from-to)	1967-1973
Number of pages	7
Journal	Clinical Cancer Research
Volume	27
Issue number	7
DOIs	https://doi.org/10.1158/1078-0432.CCR-20-3587
State	Published - Apr 2021

Funding

Research support was provided byNIHR01CA172436 (to A. Goldkorn, J.K. Pinski, S.A. Ingles, T. Triche, C. Tangen, N. Agarwal, and T. Xu), U10CA180888, U10CA180819, P30 CA014089 (to A. Goldkorn, T. Triche, G.J. Morrison, and A. Cunha), and Millennium Pharmaceuticals (Takeda Oncology). A. Goldkorn reports grants from NIH during the conduct of the study and personal fees from Albany Capital outside the submitted work; in addition, A. Goldkorn has a patent for U.S. Patent # 8,551,425 B2, 2013 issued and licensed to Corestone Biosciences, Circulogix. J.K. Pinski reports grants, personal fees, and other from NCI during the conduct of the study. D.A. Vaena reports other from NCI Cooperative Group during the conduct of the study and personal fees from AstraZeneca, Bristol Myers Squibb, Exelixis, Immunomedics, Bayer, Natera, Genomic Health, Caris, EMD Serono, and Seattle Genetics outside the submitted work. D.J. McConkey reports grants from AstraZeneca and personal fees from Janssen, Rainier Pharmaceuticals, and H3 Biomedicine outside the submitted work. M.H.A. Hussain reports grants from Northwestern University during the conduct of the study. D.I. Quinn reports grants from NCI during the conduct of the study and personal fees from Astellas, Bayer, Pfizer, AstraZeneca, and Merck outside the submitted work. N. Agarwal reports personal fees and other from Astellas, Astra-Zeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics during the conduct of the study. No disclosures were reported by the other authors.

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General Medicine

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10.1158/1078-0432.CCR-20-3587

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Goldkorn, A., Tangen, C., Plets, M., Morrison, G. J., Cunha, A., Xu, T., Pinski, J. K., Ingles, S. A., Triche, T., Harzstark, A. L., Kohli, M., MacVicar, G. R., Vaena, D. A., Crispino, A. W., McConkey, D. J., Lara, P. N., Hussain, M. H. A., Quinn, D. I., Vogelzang, N. J., ... Agarwal, N. (2021). Baseline circulating tumor cell count as a prognostic marker of PSA response and disease progression in metastatic castrate-sensitive prostate cancer (SWOG S1216). Clinical Cancer Research, 27(7), 1967-1973. https://doi.org/10.1158/1078-0432.CCR-20-3587

@article{3edeba7f26a44c61a4a60b6cf4878977,

title = "Baseline circulating tumor cell count as a prognostic marker of PSA response and disease progression in metastatic castrate-sensitive prostate cancer (SWOG S1216)",

abstract = "Purpose: In metastatic castrate-sensitive prostate cancer (mCSPC), combined androgen axis inhibition is a standard of care. Noninvasive biomarkers that guide initial therapy decisions are needed. We hypothesized that CellSearch circulating tumor cell (CTC) count, an FDA-cleared assay in metastatic castrate-resistant prostate cancer (mCRPC), is a relevant biomarker in mCSPC. Experimental Design: SWOG S1216 is a phase III prospective randomized trial of androgen deprivation therapy (ADT) combined with orteronel or bicalutamide for mCSPC. CellSearch CTC count was measured at registration (baseline). Prespecified CTC cut-off points of 0, 1-4, and ≥5 were correlated with baseline patient characteristics and, in a stratified subsample, were also correlated with two prespecified trial secondary endpoints: 7-month PSA ≤0.2 ng/mL versus 0.2-4.0 versus >4.0 (intermediate endpoint for overall survival); and progressionfree survival (PFS) ≤ versus >2 years. Results: A total of 523 patients submitted baseline samples, and CTCs were detected (median 3) in 33%. Adjusting for two trial stratification factors (disease burden and timing of ADT initiation), men with undetectable CTCs had nearly nine times the odds of attaining 7-month PSA ≤ 0.2 versus > 4.0 [OR 8.8, 95% confidence interval (CI), 2.7-28.6, P < 0.001, N = 264] and four times the odds of achieving > 2 years PFS (OR 4.0, 95% CI, 1.9-8.5, P < 0.001, N = 336) compared with men with baseline CTCs ≥5. Conclusions: Baseline CT Ccount in mCSPC is highly prognostic of 7-month PSA and 2-year PFS after adjusting for disease burden and discriminates men who are likely to experience poor survival outcomes.",

author = "Amir Goldkorn and Catherine Tangen and Melissa Plets and Morrison, {Gareth J.} and Alexander Cunha and Tong Xu and Pinski, {Jacek K.} and Ingles, {Sue A.} and Timothy Triche and Harzstark, {Andrea L.} and Manish Kohli and MacVicar, {Gary R.} and Vaena, {Daniel A.} and Crispino, {Anthony W.} and McConkey, {David J.} and Lara, {Primo N.} and Hussain, {Maha H.A.} and Quinn, {David I.} and Vogelzang, {Nicholas J.} and Thompson, {Ian Murchie} and Neeraj Agarwal",

note = "Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research.",

year = "2021",

month = apr,

doi = "10.1158/1078-0432.CCR-20-3587",

language = "English (US)",

volume = "27",

pages = "1967--1973",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "7",

}

Goldkorn, A, Tangen, C, Plets, M, Morrison, GJ, Cunha, A, Xu, T, Pinski, JK, Ingles, SA, Triche, T, Harzstark, AL, Kohli, M, MacVicar, GR, Vaena, DA, Crispino, AW, McConkey, DJ, Lara, PN, Hussain, MHA, Quinn, DI, Vogelzang, NJ, Thompson, IM & Agarwal, N 2021, 'Baseline circulating tumor cell count as a prognostic marker of PSA response and disease progression in metastatic castrate-sensitive prostate cancer (SWOG S1216)', Clinical Cancer Research, vol. 27, no. 7, pp. 1967-1973. https://doi.org/10.1158/1078-0432.CCR-20-3587

TY - JOUR

T1 - Baseline circulating tumor cell count as a prognostic marker of PSA response and disease progression in metastatic castrate-sensitive prostate cancer (SWOG S1216)

AU - Goldkorn, Amir

AU - Tangen, Catherine

AU - Plets, Melissa

AU - Morrison, Gareth J.

AU - Cunha, Alexander

AU - Xu, Tong

AU - Pinski, Jacek K.

AU - Ingles, Sue A.

AU - Triche, Timothy

AU - Harzstark, Andrea L.

AU - Kohli, Manish

AU - MacVicar, Gary R.

AU - Vaena, Daniel A.

AU - Crispino, Anthony W.

AU - McConkey, David J.

AU - Lara, Primo N.

AU - Hussain, Maha H.A.

AU - Quinn, David I.

AU - Vogelzang, Nicholas J.

AU - Thompson, Ian Murchie

AU - Agarwal, Neeraj

PY - 2021/4

Y1 - 2021/4

N2 - Purpose: In metastatic castrate-sensitive prostate cancer (mCSPC), combined androgen axis inhibition is a standard of care. Noninvasive biomarkers that guide initial therapy decisions are needed. We hypothesized that CellSearch circulating tumor cell (CTC) count, an FDA-cleared assay in metastatic castrate-resistant prostate cancer (mCRPC), is a relevant biomarker in mCSPC. Experimental Design: SWOG S1216 is a phase III prospective randomized trial of androgen deprivation therapy (ADT) combined with orteronel or bicalutamide for mCSPC. CellSearch CTC count was measured at registration (baseline). Prespecified CTC cut-off points of 0, 1-4, and ≥5 were correlated with baseline patient characteristics and, in a stratified subsample, were also correlated with two prespecified trial secondary endpoints: 7-month PSA ≤0.2 ng/mL versus 0.2-4.0 versus >4.0 (intermediate endpoint for overall survival); and progressionfree survival (PFS) ≤ versus >2 years. Results: A total of 523 patients submitted baseline samples, and CTCs were detected (median 3) in 33%. Adjusting for two trial stratification factors (disease burden and timing of ADT initiation), men with undetectable CTCs had nearly nine times the odds of attaining 7-month PSA ≤ 0.2 versus > 4.0 [OR 8.8, 95% confidence interval (CI), 2.7-28.6, P < 0.001, N = 264] and four times the odds of achieving > 2 years PFS (OR 4.0, 95% CI, 1.9-8.5, P < 0.001, N = 336) compared with men with baseline CTCs ≥5. Conclusions: Baseline CT Ccount in mCSPC is highly prognostic of 7-month PSA and 2-year PFS after adjusting for disease burden and discriminates men who are likely to experience poor survival outcomes.

AB - Purpose: In metastatic castrate-sensitive prostate cancer (mCSPC), combined androgen axis inhibition is a standard of care. Noninvasive biomarkers that guide initial therapy decisions are needed. We hypothesized that CellSearch circulating tumor cell (CTC) count, an FDA-cleared assay in metastatic castrate-resistant prostate cancer (mCRPC), is a relevant biomarker in mCSPC. Experimental Design: SWOG S1216 is a phase III prospective randomized trial of androgen deprivation therapy (ADT) combined with orteronel or bicalutamide for mCSPC. CellSearch CTC count was measured at registration (baseline). Prespecified CTC cut-off points of 0, 1-4, and ≥5 were correlated with baseline patient characteristics and, in a stratified subsample, were also correlated with two prespecified trial secondary endpoints: 7-month PSA ≤0.2 ng/mL versus 0.2-4.0 versus >4.0 (intermediate endpoint for overall survival); and progressionfree survival (PFS) ≤ versus >2 years. Results: A total of 523 patients submitted baseline samples, and CTCs were detected (median 3) in 33%. Adjusting for two trial stratification factors (disease burden and timing of ADT initiation), men with undetectable CTCs had nearly nine times the odds of attaining 7-month PSA ≤ 0.2 versus > 4.0 [OR 8.8, 95% confidence interval (CI), 2.7-28.6, P < 0.001, N = 264] and four times the odds of achieving > 2 years PFS (OR 4.0, 95% CI, 1.9-8.5, P < 0.001, N = 336) compared with men with baseline CTCs ≥5. Conclusions: Baseline CT Ccount in mCSPC is highly prognostic of 7-month PSA and 2-year PFS after adjusting for disease burden and discriminates men who are likely to experience poor survival outcomes.

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UR - http://www.scopus.com/inward/citedby.url?scp=85104847408&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-20-3587

DO - 10.1158/1078-0432.CCR-20-3587

M3 - Article

C2 - 33500355

AN - SCOPUS:85104847408

SN - 1078-0432

VL - 27

SP - 1967

EP - 1973

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 7

ER -

Baseline circulating tumor cell count as a prognostic marker of PSA response and disease progression in metastatic castrate-sensitive prostate cancer (SWOG S1216)

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