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Integration of Liquid Biopsies in Clinical Management of Metastatic Prostate Cancer

  • Genitourinary Cancers (DP Petrylak and JW Kim, Section Editors)
  • Published:
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Abstract

Purpose of Review

The field of liquid biopsies is constantly evolving through novel technologies. This review outlines current data on liquid biopsies and application to clinical management of metastatic prostate cancer.

Recent Findings

To date, there are three platforms with FDA approval for use in the setting of metastatic prostate cancer and others which have been clinically validated. There is substantial evidence supporting the use of circulating tumor cell (CTC) enumeration to guide prognosis in metastatic castration-resistant prostate cancer (mCRPC). Additional evidence supports targeted sequencing of CTC and cell-free DNA (cfDNA) to guide androgren-directed therapy, identify candidates for treatment with PARP inhibitors, and monitor development of resistance.

Summary

As a real-time and minimally invasive approach, utilization of liquid biopsies has the potential to drastically impact the treatment of metastatic prostate cancer and improve overall survival. With further clinical validation, additional liquid biopsy is likely to enter standard clinical practice.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33. https://doi.org/10.3322/caac.21654.

    Article  PubMed  Google Scholar 

  2. Chowdhury S, Bjartell A, Lumen N, Maroto P, Paiss T, Gomez-Veiga F, et al. Real-world outcomes in first-line treatment of metastatic castration-resistant prostate cancer: the prostate cancer registry. Target Oncol. 2020;15(3):301–15. https://doi.org/10.1007/s11523-020-00720-2.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Basch E, Loblaw DA, Oliver TK, Carducci M, Chen RC, Frame JN, et al. Systemic therapy in men with metastatic castration-resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol. 2014;32(30):3436–48. https://doi.org/10.1200/JCO.2013.54.8404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. National Comprehensive Cancer Network. Prostate Cancer (Version 1.2022). http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. Accessed 4 Oct 2021.

  5. Teo MY, Rathkopf DE, Kantoff P. Treatment of advanced prostate cancer. Annu Rev Med. 2019;70:479–99. https://doi.org/10.1146/annurev-med-051517-011947.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3. J Clin Oncol. 2016;34(12):1402–18. https://doi.org/10.1200/JCO.2015.64.2702.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Parker C, Castro E, Fizazi K, Heidenreich A, Ost P, Procopio G, et al. Prostate cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(9):1119–34. https://doi.org/10.1016/j.annonc.2020.06.011.

    Article  CAS  PubMed  Google Scholar 

  8. Pantel K, Alix-Panabieres C. Circulating tumour cells in cancer patients: challenges and perspectives. Trends Mol Med. 2010;16(9):398–406. https://doi.org/10.1016/j.molmed.2010.07.001.

    Article  PubMed  Google Scholar 

  9. Merker JD, Oxnard GR, Compton C, Diehn M, Hurley P, Lazar AJ, et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. J Clin Oncol. 2018;36(16):1631–41. https://doi.org/10.1200/JCO.2017.76.8671.

    Article  CAS  PubMed  Google Scholar 

  10. Shaffer DR, Leversha MA, Danila DC, Lin O, Gonzalez-Espinoza R, Gu B, et al. Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer. Clin Cancer Res. 2007;13(7):2023–9. https://doi.org/10.1158/1078-0432.CCR-06-2701.

    Article  CAS  PubMed  Google Scholar 

  11. Hodara E, Morrison G, Cunha A, Zainfeld D, Xu T, Xu Y, et al. Multiparametric liquid biopsy analysis in metastatic prostate cancer. JCI Insight. 2019;4(5). https://doi.org/10.1172/jci.insight.125529.

  12. Danila DC, Heller G, Gignac GA, Gonzalez-Espinoza R, Anand A, Tanaka E, et al. Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res. 2007;13(23):7053–8. https://doi.org/10.1158/1078-0432.CCR-07-1506.

    Article  CAS  PubMed  Google Scholar 

  13. Miller MC, Doyle GV, Terstappen LW. Significance of circulating tumor cells detected by the cellsearch system in patients with metastatic breast colorectal and prostate cancer. J Oncol. 2010;2010:617421. https://doi.org/10.1155/2010/617421.

    Article  PubMed  Google Scholar 

  14. Adams DL, Stefansson S, Haudenschild C, Martin SS, Charpentier M, Chumsri S, et al. Cytometric characterization of circulating tumor cells captured by microfiltration and their correlation to the Cell Search((R)) CTC test. Cytometry A. 2015;87(2):137–44. https://doi.org/10.1002/cyto.a.22613.

    Article  CAS  PubMed  Google Scholar 

  15. Markou A, Lazaridou M, Paraskevopoulos P, Chen S, Swierczewska M, Budna J, et al. Multiplex gene expression profiling of in vivo isolated circulating tumor cells in high-risk prostate cancer patients. Clin Chem. 2018;64(2):297–306. https://doi.org/10.1373/clinchem.2017.275503.

    Article  CAS  PubMed  Google Scholar 

  16. Agerbaek MO, Bang-Christensen SR, Yang MH, Clausen TM, Pereira MA, Sharma S, et al. The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner. Nat Commun. 2018;9(1):3279. https://doi.org/10.1038/s41467-018-05793-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kirby BJ, Jodari M, Loftus MS, Gakhar G, Pratt ED, Chanel-Vos C, et al. Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device. PLoS ONE. 2012;7(4):e35976. https://doi.org/10.1371/journal.pone.0035976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Xu L, Mao X, Imrali A, Syed F, Mutsvangwa K, Berney D, et al. Optimization and evaluation of a novel size based circulating tumor cell isolation system. PLoS ONE. 2015;10(9):e0138032. https://doi.org/10.1371/journal.pone.0138032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Vishnoi M, Peddibhotla S, Yin W, A TS, George GC, Hong DS, et al. The isolation and characterization of CTC subsets related to breast cancer dormancy. Sci Rep. 2015;5:17533. https://doi.org/10.1038/srep17533.

  20. Ozkumur E, Shah AM, Ciciliano JC, Emmink BL, Miyamoto DT, Brachtel E, et al. Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells. Sci Transl Med. 2013;5(179):179ra47. https://doi.org/10.1126/scitranslmed.3005616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Scher HI, Armstrong AJ, Schonhoft JD, Gill A, Zhao JL, Barnett E, et al. Development and validation of circulating tumour cell enumeration (epic sciences) as a prognostic biomarker in men with metastatic castration-resistant prostate cancer. Eur J Cancer. 2021;150:83–94. https://doi.org/10.1016/j.ejca.2021.02.042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kaldjian EP, Ramirez AB, Sun Y, Campton DE, Werbin JL, Varshavskaya P, et al. The RareCyte(R) platform for next-generation analysis of circulating tumor cells. Cytometry A. 2018;93(12):1220–5. https://doi.org/10.1002/cyto.a.23619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Werner SL, Graf RP, Landers M, Valenta DT, Schroeder M, Greene SB, et al. Analytical validation and capabilities of the epic CTC Platform: enrichment-free circulating tumour cell detection and characterization. J Circ Biomark. 2015;4:3. https://doi.org/10.5772/60725.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008;14(9):985–90. https://doi.org/10.1038/nm.1789.

    Article  CAS  PubMed  Google Scholar 

  25. Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368(13):1199–209. https://doi.org/10.1056/NEJMoa1213261.

    Article  CAS  PubMed  Google Scholar 

  26. Choudhury AD, Werner L, Francini E, Wei XX, Ha G, Freeman SS, et al. Tumor fraction in cell-free DNA as a biomarker in prostate cancer. JCI Insight. 2018;3(21). https://doi.org/10.1172/jci.insight.122109.

  27. Hindson BJ, Ness KD, Masquelier DA, Belgrader P, Heredia NJ, Makarewicz AJ, et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem. 2011;83(22):8604–10. https://doi.org/10.1021/ac202028g.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Diehl F, Li M, He Y, Kinzler KW, Vogelstein B, Dressman D. BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions. Nat Methods. 2006;3(7):551–9. https://doi.org/10.1038/nmeth898.

    Article  CAS  PubMed  Google Scholar 

  29. Newman AM, Lovejoy AF, Klass DM, Kurtz DM, Chabon JJ, Scherer F, et al. Integrated digital error suppression for improved detection of circulating tumor DNA. Nat Biotechnol. 2016;34(5):547–55. https://doi.org/10.1038/nbt.3520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Taavitsainen S, Annala M, Ledet E, Beja K, Miller PJ, Moses M, et al. Evaluation of commercial circulating tumor DNA test in metastatic prostate cancer. JCO Precis Oncol. 2019;3. https://doi.org/10.1200/PO.19.00014.

  31. Chen E, Cario CL, Leong L, Lopez K, Marquez CP, Li PS, et al. Cell-free DNA detection of tumor mutations in heterogeneous, localized prostate cancer via targeted, multiregion sequencing. JCO Precis Oncol. 2021;5. https://doi.org/10.1200/PO.20.00428.

  32. Wyatt AW, Annala M, Aggarwal R, Beja K, Feng F, Youngren J, et al. Concordance of circulating tumor dna and matched metastatic tissue biopsy in prostate cancer. J Natl Cancer Inst. 2017;109(12). https://doi.org/10.1093/jnci/djx118.

  33. Vandekerkhove G, Struss WJ, Annala M, Kallio HML, Khalaf D, Warner EW, et al. Circulating tumor DNA abundance and potential utility in de novo metastatic prostate cancer. Eur Urol. 2019;75(4):667–75. https://doi.org/10.1016/j.eururo.2018.12.042.

    Article  CAS  PubMed  Google Scholar 

  34. Chae YK, Davis AA, Carneiro BA, Chandra S, Mohindra N, Kalyan A, et al. Concordance between genomic alterations assessed by next-generation sequencing in tumor tissue or circulating cell-free DNA. Oncotarget. 2016;7(40):65364–73. https://doi.org/10.18632/oncotarget.11692.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gundem G, Van Loo P, Kremeyer B, Alexandrov LB, Tubio JMC, Papaemmanuil E, et al. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520(7547):353–7. https://doi.org/10.1038/nature14347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lu YT, Delijani K, Mecum A, Goldkorn A. Current status of liquid biopsies for the detection and management of prostate cancer. Cancer Manag Res. 2019;11:5271–91. https://doi.org/10.2147/CMAR.S170380.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Food and Drug Administration. FDA approves first liquid biopsy next-generation sequencing companion diagnostic test. August 7, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-liquid-biopsy-next-generation-sequencing-companion-diagnostic-test; Accessed 9/27/21.

  38. Food and Drug Administration. FDA approves liquid biopsy NGS companion diagnostic test for multiple cancers and biomarkers. November 9, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-liquid-biopsy-ngs-companion-diagnostic-test-multiple-cancers-and-biomarkers, Accessed 9/27/21.

  39. Soekmadji C, Corcoran NM, Oleinikova I, Jovanovic L, Australian Prostate Cancer Collaboration B, Ramm GA, et al. Extracellular vesicles for personalized therapy decision support in advanced metastatic cancers and its potential impact for prostate cancer. Prostate. 2017;77(14):1416–23. https://doi.org/10.1002/pros.23403.

  40. Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in exosome isolation techniques. Theranostics. 2017;7(3):789–804. https://doi.org/10.7150/thno.18133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Vagner T, Spinelli C, Minciacchi VR, Balaj L, Zandian M, Conley A, et al. Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma. J Extracell Vesicles. 2018;7(1):1505403. https://doi.org/10.1080/20013078.2018.1505403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351(8):781–91. https://doi.org/10.1056/NEJMoa040766.

    Article  CAS  PubMed  Google Scholar 

  43. de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008;14(19):6302–9. https://doi.org/10.1158/1078-0432.CCR-08-0872. First trial to show that CTC count could distinguish between favorable and unfavorable prognoses in men with mPC using a cut point of <5 vs. >= 5 CTCs per 7.5 mL blood.

    Article  CAS  PubMed  Google Scholar 

  44. Scher HI, Jia X, de Bono JS, Fleisher M, Pienta KJ, Raghavan D, et al. Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol. 2009;10(3):233–9. https://doi.org/10.1016/S1470-2045(08)70340-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Goldkorn A, Ely B, Quinn DI, Tangen CM, Fink LM, Xu T, et al. Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. J Clin Oncol. 2014;32(11):1136–42. https://doi.org/10.1200/JCO.2013.51.7417. First North American cooperative group trial to validate the cutpoint of < 5 CTCs per 7.5 mL for determining prognosis in mPC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Scher HI, Heller G, Molina A, Attard G, Danila DC, Jia X, et al. Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer. J Clin Oncol. 2015;33(12):1348–55. https://doi.org/10.1200/JCO.2014.55.3487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lozano R, Lorente D, Aragon IM, Romero-Laorden N, Nombela P, Mateo J, et al. Value of early circulating tumor cells dynamics to estimate docetaxel benefit in metastatic castration-resistant prostate cancer (mCRPC) patients. Cancers (Basel). 2021;13(10). https://doi.org/10.3390/cancers13102334. Clinical trial supporting decrease in CTC counts as biomarker of treatment response

  48. Chang K, Kong YY, Dai B, Ye DW, Qu YY, Wang Y, et al. Combination of circulating tumor cell enumeration and tumor marker detection in predicting prognosis and treatment effect in metastatic castration-resistant prostate cancer. Oncotarget. 2015;6(39):41825–36. https://doi.org/10.18632/oncotarget.6167.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Scher HI, Heller G, Molina A, Kheoh T, Attard G, Moreira J, et al. Evaluation of circulating tumor cell (CTC) enumeration as an efficacy response biomarker of overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC): planned final analysis (FA) of COU-AA-301, a randomized, double-blind, placebo-controlled, phase III study of abiraterone acetate (AA) plus low-dose prednisone (P) post docetaxel. J Clin Oncol. 2011;29:293s (suppl; abstr LBA4517).

  50. Lorente D, Olmos D, Mateo J, Bianchini D, Seed G, Fleisher M, et al. Decline in circulating tumor cell count and treatment outcome in advanced prostate cancer. Eur Urol. 2016;70(6):985–92. https://doi.org/10.1016/j.eururo.2016.05.023.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Heller G, Fizazi K, McCormack R, Molina A, MacLean D, Webb IJ, et al. The added value of circulating tumor cell enumeration to standard markers in assessing prognosis in a metastatic castration-resistant prostate cancer population. Clin Cancer Res. 2017;23(8):1967–73. https://doi.org/10.1158/1078-0432.CCR-16-1224.

    Article  CAS  PubMed  Google Scholar 

  52. Heller G, McCormack R, Kheoh T, Molina A, Smith MR, Dreicer R, et al. Circulating tumor cell number as a response measure of prolonged survival for metastatic castration-resistant prostate cancer: a comparison with prostate-specific antigen across five randomized phase iii clinical trials. J Clin Oncol. 2018;36(6):572–80. https://doi.org/10.1200/JCO.2017.75.2998. Pooled analysis of 5 trials comparing different cut off points for evaluating treatment response using CTC counts

    Article  CAS  PubMed  Google Scholar 

  53. Lorente D, Olmos D, Mateo J, Dolling D, Bianchini D, Seed G, et al. Circulating tumour cell increase as a biomarker of disease progression in metastatic castration-resistant prostate cancer patients with low baseline CTC counts. Ann Oncol. 2018;29(7):1554–60. https://doi.org/10.1093/annonc/mdy172. Clinical trial showing that any increase in CTC count after baseline is associated with worse survival outcomes

    Article  CAS  PubMed  Google Scholar 

  54. Goldkorn A, Tangen C, Plets M, Morrison GJ, Cunha A, Xu T, et al. Baseline circulating tumor cell count as a prognostic marker of PSA response and disease progression in metastatic castrate-sensitive prostate cancer (SWOG S1216). Clin Cancer Res. 2021;27(7):1967–73. https://doi.org/10.1158/1078-0432.CCR-20-3587. Clinical study validating CTC count as biomarker in mHSPC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Goodman OB Jr, Symanowski JT, Loudyi A, Fink LM, Ward DC, Vogelzang NJ. Circulating tumor cells as a predictive biomarker in patients with hormone-sensitive prostate cancer. Clin Genitourin Cancer. 2011;9(1):31–8. https://doi.org/10.1016/j.clgc.2011.04.001.

    Article  PubMed  Google Scholar 

  56. Resel Folkersma L, San Jose Manso L, Galante Romo I, Moreno Sierra J, Olivier Gomez C. Prognostic significance of circulating tumor cell count in patients with metastatic hormone-sensitive prostate cancer. Urology. 2012;80(6):1328–32. https://doi.org/10.1016/j.urology.2012.09.001.

  57. Yu EY, Li H, Higano CS, Agarwal N, Pal SK, Alva A, et al. SWOG S0925: a randomized phase II study of androgen deprivation combined with cixutumumab versus androgen deprivation alone in patients with new metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2015;33(14):1601–8. https://doi.org/10.1200/JCO.2014.59.4127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161(5):1215–28. https://doi.org/10.1016/j.cell.2015.05.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Azad AA, Volik SV, Wyatt AW, Haegert A, Le Bihan S, Bell RH, et al. Androgen receptor gene aberrations in circulating cell-free DNA: biomarkers of therapeutic resistance in castration-resistant prostate cancer. Clin Cancer Res. 2015;21(10):2315–24. https://doi.org/10.1158/1078-0432.CCR-14-2666.

    Article  CAS  PubMed  Google Scholar 

  60. Conteduca V, Wetterskog D, Sharabiani MTA, Grande E, Fernandez-Perez MP, Jayaram A, et al. Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study. Ann Oncol. 2017;28(7):1508–16. https://doi.org/10.1093/annonc/mdx155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Annala M, Vandekerkhove G, Khalaf D, Taavitsainen S, Beja K, Warner EW, et al. Circulating tumor DNA genomics correlate with resistance to abiraterone and enzalutamide in prostate cancer. Cancer Discov. 2018;8(4):444–57. https://doi.org/10.1158/2159-8290.CD-17-0937.

    Article  CAS  PubMed  Google Scholar 

  62. Cancer Genome Atlas Research Network. The molecular taxonomy of primary prostate cancer. Cell. 2015;163(4):1011–25. https://doi.org/10.1016/j.cell.2015.10.025.

    Article  CAS  Google Scholar 

  63. Watson PA, Arora VK, Sawyers CL. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer. 2015;15(12):701–11. https://doi.org/10.1038/nrc4016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lu D, Krupa R, Harvey M, Graf RP, Schreiber N, Barnett E, et al. Development of an immunofluorescent AR-V7 circulating tumor cell assay - a blood-based test for men with metastatic prostate cancer. J Circ Biomark. 2020;9:13–9. https://doi.org/10.33393/jcb.2020.2163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lokhandwala PM, Riel SL, Haley L, Lu C, Chen Y, Silberstein J, et al. Analytical validation of androgen receptor splice variant 7 detection in a clinical laboratory improvement amendments (CLIA) laboratory setting. J Mol Diagn. 2017;19(1):115–25. https://doi.org/10.1016/j.jmoldx.2016.08.003.

    Article  CAS  PubMed  Google Scholar 

  66. Scher HI, Lu D, Schreiber NA, Louw J, Graf RP, Vargas HA, et al. Association of AR-V7 on circulating tumor cells as a treatment-specific biomarker with outcomes and survival in castration-resistant prostate cancer. JAMA Oncol. 2016;2(11):1441–9. https://doi.org/10.1001/jamaoncol.2016.1828.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Scher HI, Graf RP, Schreiber NA, Jayaram A, Winquist E, McLaughlin B, et al. Assessment of the validity of nuclear-localized androgen receptor splice variant 7 in Circulating tumor cells as a predictive biomarker for castration-resistant prostate cancer. JAMA Oncol. 2018;4(9):1179–86. https://doi.org/10.1001/jamaoncol.2018.1621. Clinical trial validating use of AR-V7 for selection of ARPIs vs. taxanes as first line treatment

    Article  PubMed  PubMed Central  Google Scholar 

  68. Armstrong AJ, Halabi S, Luo J, Nanus DM, Giannakakou P, Szmulewitz RZ, et al. Prospective multicenter validation of androgen receptor splice variant 7 and hormone therapy resistance in high-risk castration-resistant prostate cancer: the PROPHECY study. J Clin Oncol. 2019;37(13):1120–9. https://doi.org/10.1200/JCO.18.01731. Clinical trial demonstrating worse survival outcomes in patients with AR-V7 treated with ARPIs

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Armstrong AJ, Luo J, Nanus DM, Giannakakou P, Szmulewitz RZ, Danila DC, et al. Prospective multicenter study of circulating tumor cell AR-V7 and taxane versus hormonal treatment outcomes in metastatic castration-resistant prostate cancer. JCO Precis Oncol. 2020;4. https://doi.org/10.1200/PO.20.00200. Clinical trial showing no difference in survival outcomes by AR-V7 status in patients receiving taxane therapy after progression on ARPIs

  70. Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014;371(11):1028–38. https://doi.org/10.1056/NEJMoa1315815. First trial to show association between AR-V7 status (using AdnaTest) and treatment response in mPC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Brown LC, Lu C, Antonarakis ES, Luo J, Armstrong AJ. Androgen receptor variant-driven prostate cancer II: advances in clinical investigation. Prostate Cancer Prostatic Dis. 2020;23(3):367–80. https://doi.org/10.1038/s41391-020-0215-5.

    Article  CAS  PubMed  Google Scholar 

  72. Graf RP, Hullings M, Barnett ES, Carbone E, Dittamore R, Scher HI. Clinical utility of the nuclear-localized AR-V7 biomarker in circulating tumor cells in improving physician treatment choice in castration-resistant prostate cancer. Eur Urol. 2020;77(2):170–7. https://doi.org/10.1016/j.eururo.2019.08.020.

    Article  CAS  PubMed  Google Scholar 

  73. de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wulfing C, et al. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med. 2019;381(26):2506–18. https://doi.org/10.1056/NEJMoa1911206.

    Article  PubMed  Google Scholar 

  74. Castro E, Romero-Laorden N, Del Pozo A, Lozano R, Medina A, Puente J, et al. PROREPAIR-B: a prospective cohort study of the impact of germline DNA repair mutations on the outcomes of patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(6):490–503. https://doi.org/10.1200/JCO.18.00358. Clinical study demonstrating that patients with BRCA2 mutations have worse CSS when treated with taxanes as first-line treatment, but not when treated with ARPIs first

    Article  CAS  PubMed  Google Scholar 

  75. Lord CJ, Ashworth A. PARP inhibitors: SYNTHETIC lethality in the clinic. Science. 2017;355(6330):1152–8. https://doi.org/10.1126/science.aam7344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;373(18):1697–708. https://doi.org/10.1056/NEJMoa1506859. First trial to show that HRD mutations could identify patients with mPC most likely to respond to PARPi treatment.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Goodall J, Mateo J, Yuan W, Mossop H, Porta N, Miranda S, et al. Circulating cell-free DNA to guide prostate cancer treatment with PARP inhibition. Cancer Discov. 2017;7(9):1006–17. https://doi.org/10.1158/2159-8290.CD-17-0261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020;382(22):2091–102. https://doi.org/10.1056/NEJMoa1911440. Clinical trial showing benefit of PARPi olaparib in patients with HRR deficiency mutations

    Article  PubMed  Google Scholar 

  79. Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med. 2020;383(24):2345–57. https://doi.org/10.1056/NEJMoa2022485. Final analysis of PROfound study showing improved survival in patients with BRCA1, BRCA2, or ATM mutations who received the PARPi olaparib

    Article  CAS  PubMed  Google Scholar 

  80. Abida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, et al. Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration. J Clin Oncol. 2020;38(32):3763–72. https://doi.org/10.1200/JCO.20.01035. Clinical study evaluating efficacy of rucaparib showed high ORR in patients with BRCA1 or BRCA2 mutations who had previously progressed on ARPIs or taxanes

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Quigley D, Alumkal JJ, Wyatt AW, Kothari V, Foye A, Lloyd P, et al. Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors. Cancer Discov. 2017;7(9):999–1005. https://doi.org/10.1158/2159-8290.CD-17-0146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Gerdtsson E, Pore M, Thiele JA, Gerdtsson AS, Malihi PD, Nevarez R, et al. Multiplex protein detection on circulating tumor cells from liquid biopsies using imaging mass cytometry. Converg Sci Phys Oncol. 2018;4(1). https://doi.org/10.1088/2057-1739/aaa013.

  83. Miyamoto DT, Lee RJ, Kalinich M, LiCausi JA, Zheng Y, Chen T, et al. An RNA-based digital circulating tumor cell signature is predictive of drug response and early dissemination in prostate cancer. Cancer Discov. 2018;8(3):288–303. https://doi.org/10.1158/2159-8290.CD-16-1406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Herberts C, Murtha AJ, Fu S, Wang G, Schonlau E, Xue H, et al. Activating AKT1 and PIK3CA mutations in metastatic castration-resistant prostate cancer. Eur Urol. 2020;78(6):834–44. https://doi.org/10.1016/j.eururo.2020.04.058.

    Article  CAS  PubMed  Google Scholar 

  85. Zviran A, Schulman RC, Shah M, Hill STK, Deochand S, Khamnei CC, et al. Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring. Nat Med. 2020;26(7):1114–24. https://doi.org/10.1038/s41591-020-0915-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Faugeroux V, Lefebvre C, Pailler E, Pierron V, Marcaillou C, Tourlet S, et al. An accessible and unique insight into metastasis mutational content through whole-exome sequencing of circulating tumor cells in metastatic prostate cancer. Eur Urol Oncol. 2020;3(4):498–508. https://doi.org/10.1016/j.euo.2018.12.005.

    Article  PubMed  Google Scholar 

  87. Silva R, Moran B, Baird AM, O’Rourke CJ, Finn SP, McDermott R, et al. Longitudinal analysis of individual cfDNA methylome patterns in metastatic prostate cancer. Clin Epigenetics. 2021;13(1):168. https://doi.org/10.1186/s13148-021-01155-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Zhao SG, Chen WS, Li H, Foye A, Zhang M, Sjostrom M, et al. The DNA methylation landscape of advanced prostate cancer. Nat Genet. 2020;52(8):778–89. https://doi.org/10.1038/s41588-020-0648-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Wu A, Cremaschi P, Wetterskog D, Conteduca V, Franceschini GM, Kleftogiannis D, et al. Genome-wide plasma DNA methylation features of metastatic prostate cancer. J Clin Invest. 2020;130(4):1991–2000. https://doi.org/10.1172/JCI130887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This work was funded in part by P30CA014089 to the Norris Comprehensive Cancer Center.

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Authors and Affiliations

  1. Division of Medical Oncology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Varsha Tulpule, Gareth J. Morrison, David I. Quinn & Amir Goldkorn

  2. Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Mary Falcone, David I. Quinn & Amir Goldkorn

  3. Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Amir Goldkorn

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  1. Varsha Tulpule
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  2. Gareth J. Morrison
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  4. David I. Quinn
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Correspondence to Amir Goldkorn.

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Dr. Quinn reports personal fees from Bayer, Astellas, Pfizer, Dendreon, Merck, Genentech/Roche, Clinigen, Aveo, Exelixis, Seagen, BMS, EMD Serono, Eisai, and Novartis. Dr. Falcone reports grants from National Cancer Institute during the conduct of the study.

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Tulpule, V., Morrison, G.J., Falcone, M. et al. Integration of Liquid Biopsies in Clinical Management of Metastatic Prostate Cancer. Curr Oncol Rep 24, 1287–1298 (2022). https://doi.org/10.1007/s11912-022-01278-0

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