Potential clinical application of the cancer antigen CA‑62 for differential diagnosis of prostate cancer and benign prostatic hyperplasia at the elevated prostate‑specific antigen

Purpose of the study. Evaluation of the diagnostic characteristics of the CA‑62 marker for epithelial carcinomas for detecting early‑stage prostate cancer in a double‑blind clinical study. This study is also focused on the possibility of using the CA‑62 antigen as an auxiliary tool for decision‑making in prostate cancer diagnosis.

Patients and methods. A blinded clinical study was conducted on 325 clinically verified blood serum samples. This includes 144 prostate cancer samples, 79 generally healthy volunteers‑men and 102 samples from patients with benign prostatic hyperplasia (BPH). Quantitative determination of the total and free prostate specific antigen (PSA) levels, as well as the CA‑62 marker of serum samples was performed using the electrochemiluminescent immunoassay ECLIA Elecsys Total and Free PSA (COBAS, Roche Diagnostics GmbH, Germany, EU) and the chemiluminescent immunoassay CLIA‑CA‑62 (JVS Diagnostics LLC, Moscow, RF).

Results. A comparison of the CA‑62 level with the results for total and free PSA, as well as other diagnostic methods (PCA3, PHI) for the analysis of the BPH and prostate cancer groups was performed. The results show that the CA‑62 marker has the highest PPV (94.4 %) and NPV (93.1 %). This may increase the reliability of the decision related to the presence of PC and be used by doctors as an argument as an argument for a prostate biopsy referral. It has been demonstrated that using the novel cancer marker CA‑62 makes it possible to detect up to 90 % of the early‑stage prostate cancer with 97.2 % specificity (AUC = 0.969).

Conclusion. Using the CA‑62 marker as an auxiliary diagnostic method within the PSA “grey zone” (from 2.5 to 10 ng/ml) made it possible to significantly increase the accuracy of detecting the PC early stages at biopsy up to 93.1 %. It will help the doctors to effectively differentiate between prostate cancer and benign prostatic hyperplasia.

1. International Agency for Research on Cancer. GLOBOCAN 2020: Cancer incidence and mortality worldwide in 2020. Available at: https://gco.iarc.fr/today/fact-sheets-cancers. Accessed: 10.02.2023.

2. Malignant neoplasms in Russia in 2020 (morbidity and mortality). Edited by Kaprin AD, Starinsky VV, Shakhzadova AO. Мoscow: P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Radiology Research Centre of the Ministry of Health of the Russian Federation, 2021, 252 p. (In Russ.). Available at: https://glavonco.ru/cancer_register/Забол_2020_Электр.pdf. Accessed: 10.02.2023.

3. Каприн А. Д. Алексеев Б. Я., Матвеев В. Б., Пушкарь Д. Ю., Говоров А. В., Горбань Н. А., и др. Рак предстательной железы. Клинические рекомендации. Современная онкология. 2021;23(2):211–247. https://doi.org/10.26442/18151434.2021.2.200959

4. Guide to cancer early diagnosis. World Health Organization, 2018, ISBN 978‑92‑4‑451194‑7. Available at: https://apps.who.int/iris/bitstream/handle/10665/272264/9789244511947-rus.pdf. Accessed 10.02.2023.

5. Lundgren PO, Kjellman A, Norming U, Gustafsson O. Long‑Term Outcome of a Single Intervention Population Based Prostate Cancer Screening Study. J Urol. 2018 Jul;200(1):82–88. https://doi.org/10.1016/j.juro.2018.01.080

6. Misra‑Hebert AD, Hu B, Klein EA, Stephenson A, Taksler GB, Kattan MW, Rothberg MB. Prostate cancer screening practices in a large, integrated health system: 2007‑2014. BJU Int. 2017 Aug;120(2):257–264. https://doi.org/10.1111/bju.13793

7. Vickers AJ. Prostate Cancer Screening: Time to Question How to Optimize the Ratio of Benefits and Harms. Ann Intern Med. 2017 Oct 3;167(7):509–510. https://doi.org/10.7326/m17‑2012

8. Jahn JL, Giovannucci EL, Stampfer MJ. The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology and treatment of prostate cancer in the Prostate‑specific Antigen‑era. Int J Cancer. 2015 Dec 15;137(12):2795–2802. https://doi.org/10.1002/ijc.29408

9. Sergeeva NS, Skachkova TE, Marshutina NV, Alekseev BYa, Kaprin AD. Clinical significance of psa‑associated tests in the diagnosis and staging of prostate cancer. P.A. Herzen Journal of Oncology. 2018;7(1):55–67. (In Russ.). https://doi.org/10.17116/onkolog20187155‑67

10. Verbeek JFM, Bangma CH, Kweldam CF, van der Kwast TH, Kümmerlin IP, van Leenders GJLH, Roobol MJ. Reducing unnecessary biopsies while detecting clinically significant prostate cancer including cribriform growth with the ERSPC Rotterdam risk calculator and 4Kscore. Urol Oncol. 2019 Feb;37(2):138–144. https://doi.org/10.1016/j.urolonc.2018.11.021

11. Detsky JS, Ghiam AF, Mamedov A, Commisso K, Commisso A, Zhang L, et al. Impact of Biopsy Compliance on Outcomes for Patients on Active Surveillance for Prostate Cancer. J Urol. 2020 Nov;204(5):934–940. https://doi.org/10.1097/ju.0000000000001091

12. Collins GN, Lloyd SN, Hehir M, McKelvie GB. Multiple transrectal ultrasound‑guided prostatic biopsies‑‑true morbidity and patient acceptance. Br J Urol. 1993 Apr;71(4):460–463. https://doi.org/10.1111/j.1464‑410x.1993.tb15993.x

13. Демин А. А., Говоров А. В., Васильев А. О. и др. Современный взгляд на биопсию предстательной железы. Consilium Medicum. 2018;20(7):11–14. https://doi.org/10.26442/2075‑1753_2018.7.11‑14

14. Tcherkassova J, Prostyakova A, Tsurkan S, Ragoulin V, Boroda A, Sekacheva M. Diagnostic efficacy of the new prospective biomarker’s combination CA 15‑3 and CA‑62 for early‑stage breast cancer detection: Results of the blind prospective‑retrospective clinical study. Cancer Biomark. 2022;35(1):57–69. https://doi.org/10.3233/cbm‑210533

15. Cherkasova JR, Tsurkan SA, Kondratiev VB, Moro‑Vidal R. Cancer antigen for early cancer detection. Patent RU2020114411A, WO2021215955A1 (2021). Available at: https://patents.google.com/patent/WO2021215955A1/en?oq=WO2021215955A1

16. RF patent RU2735918C2 A set of reagents for the detection of a marker of epithelial carcinomas. 2018. (In Russ.).

17. Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017.

18. Cohen J. A coefficient of agreement for nominal scales. Educational and Psychological Measurement. 1960;20:37–46.

19. Fleiss JL, Levin B, Paik MC. Statistical Methods for Rates and Proportions. 3rd ed. New York: Wiley; 2003.

20. Gilchrist JM. Weighted 2 x 2 kappa coefficients: recommended indices of diagnostic accuracy for evidence‑based practice. J Clin Epidemiol. 2009 Oct;62(10):1045–1053. https://doi.org/10.1016/j.jclinepi.2008.11.012

21. Thomsen FB, Westerberg M, Garmo H, Robinson D, Holmberg L, Ulmert HD, Stattin P. Prediction of metastatic prostate cancer by prostate‑specific antigen in combination with T stage and Gleason Grade: Nationwide, population‑based register study. PLoS One. 2020 Jan 29;15(1):e0228447. https://doi.org/10.1371/journal.pone.0228447

22. Roddam AW, Rimmer J, Nickerson C, Ward AM; NHS Prostate Cancer Risk Management Programme. Prostate‑specific antigen: bias and molarity of commercial assays for PSA in use in England. Ann Clin Biochem. 2006 Jan;43(Pt 1):35–48. https://doi.org/10.1258/000456306775141731

23. Scott RJ, Mehta A, Macedo GS, Borisov PS, Kanesvaran R, El Metnawy W. Genetic testing for homologous recombination repair (HRR) in metastatic castration‑resistant prostate cancer (mCRPC): challenges and solutions. Oncotarget. 2021 Aug 3;12(16):1600–1614. https://doi.org/10.18632/oncotarget.28015

24. Musaelyan AA, Nazarov VD, Lapin SV, Boriskin AG, Reva SA, Lebedev DG, et al. Diagnostic value of PCA3, TMPRSS2:ERG and prostatic specific antigen derivatives in the detection of prostate cancer. Cancer Urology. 2020;16(2):65–73. (In Russ.). https://doi.org/10.17650/1726‑9776‑2020‑16‑2‑65‑73

25. Balk SP, Ko YJ, Bubley GJ. Biology of prostate‑specific antigen. J Clin Oncol. 2003 Jan 15;21(2):383–391. https://doi.org/10.1200/jco.2003.02.083

26. Kimura T, Sato S, Takahashi H, Egawa S. Global Trends of Latent Prostate Cancer in Autopsy Studies. Cancers (Basel). 2021 Jan 19;13(2):359. https://doi.org/10.3390/cancers13020359

27. Ha H, Chung JW, Ha YS, Choi SH, Lee JN, Kim BS, et al. Clinical significance of the De Ritis ratio for detecting prostate cancer in a repeat prostate biopsy. Investig Clin Urol. 2019 Nov;60(6):447–453. https://doi.org/10.4111/icu.2019.60.6.447

28. Govorov AV, Vasilev AO, Shiryaev AA, Brodetskii BM, Sadchenko AV, Kovylina MV, et al. Comparative analysis of the results of prostate biopsy under the control of TRUS, the HistoscanningTM system and MRI: the choice of optimal tactics for the detection of prostate cancer. Proceedings of the 12th International Congress of the Russian Society of Oncourologists. Мoscow, 2017, pp. 20–21. (In Russ.). Available at: https://www.calameo.com/books/0045207367ad73a665cd2. Accessed: 10.02.2023

29. Detsky J, Ghiam AF, Mamedov A, Commisso K, Commisso A, Klotz L, et al. Impact of compliance on outcomes for patients on active surveillance for prostate cancer. Journal of Clinical Oncology. 2019;37(7):36–36. DOI: 10.1200/JCO.2019.37.7_suppl.36

30. Apolikhin OI, Sivkov AV, Shishkin SV, Sheyman IM, Son IM, Katibov MI, et al. Medical and economic aspects of a comprehensive program of staged standardized diagnostics and treatment of benign prostatic hyperplsia. Experimental and Clinical Urology. 2014;3:4‑8. (In Russ.).