The Role of the Latest Biomarkers, the Gleason Tertiary Index, and Comorbid Status in Improving the Detection of High-risk Hormone-untreated Non-metastatic Prostate Cancer

С. В. Головко


The objective of the study was to confirm additional criteria that do not include indicators of the standard classification of Tumor-Node-Metastasis (TNM), prostate-specific antigen (PSA) and standard Gleason indicators to improve the stratification of high-risk non-metastatic prostate cancer (RP). A detailed analysis of the literature was performed using PubMed data, which provided additional approaches to the standard classification. Treatment of prostate cancer should be based on the stratification of risk factors, which will ensure that the therapy corresponds to the degree of aggressiveness of the disease.

The study made the following conclusions:

1. Identification of the latest biomarkers contributes to a more thorough study of the characteristics of RP. These indicators provide greater potential both in diagnostic and prognostic terms.

2. treatment Options for men at high risk of prostate-cancer-specific death (i.e. patients with a Charleson index >3) should take into account the high level of competing lethality.

3. Within the high-risk cohort, patients with multiple risk factors represent the group with the worst prognosis for prostate-specific mortality.

4. Modern approaches to the definition of high-risk non-metastatic breast cancer contribute to a more accurate prediction of cancer-specific survival (CSR).


prostate cancer; high-risk prostate cancer; risk stratification


Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.

D’Amico AV, Whittington R, Malcowicz SB et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998;280:969–74.

Bill-Axelson A, Holmberg L, Filen F et al. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst 2008;100:1144–54.

Thompson IM, Targen CM, Paradelo J et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 2009;181:956–62.

Taverna G, Benecchi L, Grizzi F et al. Can a Gleason 6 or less microfocus of prostate cancer in one biopsy and prostate-specific antigen level <10ng/mL be defined as the archetype of low-risk prostate disease? J Oncol 2012;2012:6451.

Roach M III, Waldman F, Pollack A. Predictive models in external beam radiotherapy for clinically localized prostate cancer. Cancer 2009;115(13 Suppl):3112–20.

Beauval JB, Ploussard G, Soulie M et al. Pathologic findings in radical prostatectomy specimens from patients eligible for active surveillance with highly selective criteria: a multicenter study. Urology 2012;80:656–60.

Bastian PJ, Boorjian SA, Bossi A et al. High-risk prostate cancer: from definition to contemporary management. Eur Urol 2012;61:1096–106.

Rosental SA, Sandler HM. Treatment strategies for high-risk locally advanced prostate cancer. Nat Rev Urol 2010;7:31–8.

M.Mossannen, K.G.Nepple, R.L.Grubb 3rd et al. Heterogenety in definitions of high-risk prostate cancer and varying on mortality rates after radical prostatectomy. Eur Urol Oncol 2018; 122:143–148.

Durand X, Xylinas E, Radulascu C et al. The value of urinary prostate cancer gene (PCA 3) scores in predicting pathological features at radical prostatectomy. BJU Int 2012;110:43–49.

Van Poppel H, Haese A, Graefen M et al. The relationship between Prostate Cancer gene 3 (PCA 3) and prostate cancer significance. BJU Int 2012;109:360–6.

Hessels D, van Gils MP, van Hooij O et al. Predictive value of PCA 3 in urinary sediments in determining clinicopathological characteristics of prostate cancer. Prostate 2010;70:10–16.

Van Gils MP, Hessels D, Hulsbergen-Van de Kaa CA et al. Detailed analysis of histopathological parameters in radical prostatectomy speciments and PCA 3 urinary test results. Prostate 2008;68:1215–22.

Koksal IT, Dirice E, Yasar D et al. The assessment of PTEN tumor suppressor gene in combination with Gleason scoring and serum PSA to evaluate progression of prostate carcinoma. Urol Oncol 2004;22:307–12.

Lotan TL, Gurel B, Sutcliffe S et al. PTEN protein loss by immunostaining: validation and prognostic indicator for a high risk surgical cohort of prostate cancer patients. Clin Cancer Res 2001;17:6563–73.

Guzick J, Swanson GP, Fisher G et al. Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. Lancet Oncology 2011;12:245–55.

Guzick J, Berney DM, Fisher G et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer 2012;106:1095–9.

Hoogland AM, Jenster G, van Weerden WM et al. ERG immunochemistry is not predictive for PSA recurrence, local recurrence or overall survival after radical prostatectomy for prostate cancer. Mod Pathol 2012;25:471–9.

Sreenath TL, Dobi A, Petrovich G, Srivastava S. Oncologic activation of ERG: a predominant mechanism in prostate cancer. J Carcinog 2012;11:37. Available at: http:/ Accessed October 2013.

Nam RK, Sugar L, Yang W et al. Expression of the TMPRSS2: ERG fusion gene predicts cancer recurrence after surgery for localized prostate cancer. Br J Cancer 2007;97:1690–5.

Demichelis F, Fall K, Perner S et al. TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort. Oncogene 2007;26:4596–9.

Shah RB, Daignault S, Kunju LP, Wood JDP, Wej JT. Significance of tertiary pattern 5 in prostate needle biopsies with Gleason score of 3+4 or 4+3 prostate cancer: pathologic correlation following radical prostatectomy. Mod Pathol 2009;22 (Suppl.1):193A (Abstract #873).

Nanda A, Chen MH, Renshaw AA, D-Amico AV. Gleason Pattern 5 prostate cancer: further stratification of patients with high-risk disease and implications for future randomized trials. Int J Radiat Oncol Biol Phys 2009;74:1419–23.

Nguyen PL, Chen MH, Catalona WJ, Moul JW, Sun L, DꞌAmico AV. Predicting prostate cancer mortality among men with intermediate to high-risk disease and multiple unfavorable risk factors. Int J Radiat Oncol Biol Phys 2009;73:659–64.

Loeb S, Schaeffer EM, Trock BJ, Epstein JI, Humphreys EB, Walsh PC. What are the outcomes of radical prostatectomy for high-risk prostate cancer? Urology 2010;76:710–4.

Tendulkar RD, Reddy CA, Stephans KL et al. Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. Int J Radiat Oncol Biol Phys 2012;82:1397–404.

Daskivich TJ, Chamie K, Kwan L et al. Comorbidity and competing risks for mortality in men with prostate cancer. Cancer 2011;117:4642–50.

Yossepowitch O, Eggener SE, Serio AM et al. Secondary therapy, metastatic progression, and cancerspecific mortality in men with clinically high-risk prostate cancer treated with radical prostatectomy. Eur Urol 2008;53:950–9.

Muglia VF, Westphalen AC, Wang ZJ, Kurhanewicz J, Carrol PR, Coakley FV. Endorectal MRI of prostate cancer: incremental prognostic importance of gross locally advanced disease. AJR Am J Roentgenol 2011;197:1369–74.

Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostate Carcinoma. Am J Surg Pathol 2005;29:1228–42.

Pierorazio PM, Ross AE, Lin BM et al. Preoperative characteristics of high-Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy. BJU Int 2012;110:1122–8.

Charlson ME, Pompei P, Alex KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373–83.

Nguyen PL, Chen MH, Beard CJ et al. Comorbidity, body mass index, and age and the risk of nonprostate-cancerspecific mortality after a postradiation prostate-specific antigen recurrence. Cancer 2010;116:610–5.

Kutikov A, Cooperberg MR, Paciorek AT, Uzzo RG, Carroll PR, Boorjian SA. Evaluating prostate cancer mortality and competing risks of death in patients with localized prostate cancer using a comprehensive nomogram. Prostate Cancer Prostatic Dis 2012;15:374–9.

Daskivich TJ, Fan KH, Koyama T et al. Effect of age, tumor risk, and comorbidity on competing risks for survival in a u.s. Population-based cohort of men with prostate cancer. Ann Intern Med 2013;158:709–17.

Vickers A, Benette C, Steineck G et al. Individualized estimation of the benefit of radical prostatectomy from the Scandinavian Prostate Cancer Group randomized trial. Eur Urol 2012;62:204–9.

Hamstra DA, Bae K, Pilepich MV et al. Older age predicts decreased metastasis and prostate cancer-specific death for men treated with radiation therapy: metaanalysis of radiation therapy oncology group trials. Int J Radiat Oncol Biol Phys 2011;81:1293–301.

Widmark A, Klepp O, Solberg A et al. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer ( SPCG-7/SFUO-3): an open randomized phase III trial. Lancet 2009;373:301–8.

Warde P, Mason M, Ding K et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomized, phase 3 trial. Lancet 2011;378:2104–11.

Bechis SK, Carroll PR, Cooperberg MR. Impact of age at diagnosis on prostate cancer treatment and survival. J Clin Oncol 2011;29:235–41.

Huang J, Vicini FA, Williams SG et al. Percentage of positive biopsy cores: a better risk stratification model for prostate cancer? Int J Radiat Oncol Biol Phys 2012;83:1141–8.

Yokomizo A, Murai M, Baba S et al. Percentage of positive biopsy cores, preoperative prostate-specific antigen (PSA) lewel , pT and Gleason score as prediction of PSA recurrence after radical prostatectomy: a multi-institutional outcome study in Japan. BJU Int 2006;98:549–53.

Hayashi N, Urashima M, Kuruma H et al. The maximum tumour length in biopsy cores as a predictor of outcome after radical prostatectomy. BJU Int 2008;101:175–80.

D’Amico AV, Whittington R, Malkowicz SB et al. A multivariable analysis of clinical factors predicting for pathological features associated with local failure after radical prostatectomy for prostate cancer. Int J Radiat Oncol Biol Phys 1994;30:293–302.

Roethke MC, Lichy MP, Kniess M et al. Accuracy of preoperative endorectal MRI in predicting extracapsular extension and influence on neurovascular bundle sparing in radical prostatectomy. World J Urol 2013;31:1111–6.

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