|
|
EDITORIAL |
|
Year : 2017 | Volume
: 44
| Issue : 3 | Page : 119-120 |
|
Urinary tumor markers in prostate cancer
Shridhar C Ghagane1, Rajendra B Nerli2
1 Department of Urology, KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, Karnataka, India 2 KLES Dr. Prabhakar Kore Hospital and Medical Research Centre; Department of Urology, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India
Date of Web Publication | 14-Feb-2018 |
Correspondence Address: Rajendra B Nerli Kles Kidney Foundation, KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi - 590 010, Karnataka India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jss.JSS_1_18
How to cite this article: Ghagane SC, Nerli RB. Urinary tumor markers in prostate cancer. J Sci Soc 2017;44:119-20 |
Prostate cancer is one of the most common malignancies in men worldwide.[1] Recent studies have shown that approximately 220,800 men in the United States were diagnosed with prostate cancer, and approximately 27,540 men in the United States succumbed to prostate cancer.[2] Approximately 98% of prostate cancer cases are of glandular origin,[3] and the microscopic diagnosis of prostatic adenocarcinoma is based primarily on the appearance of the glands, their formation, and pattern. Prostatic cancer (PC) is rarely symptomatic early in its course, as the majority of malignancies arise in the peripheral portion of the gland away from the prostatic urethra. Symptomatic presentation often implies local extension or even metastatic disease.[4] As the cancer begins to involve the urethra and/or bladder neck, obstructive voiding symptoms often develop. It becomes all the more difficult to attribute these symptoms to cancer, as they are also associated with benign prostatic hyperplasia (BPH). Prostate-specific antigen (PSA) is widely used to screen for prostate cancer. PSA screening is less expensive than transrectal ultrasound (TRUS), and it can detect more prostate cancers than digital rectal examination (DRE) or TRUS, and is more likely to be organ- confined compared to those cancers discovered by DRE alone.[5],[6],[7] However, it is not recommended to use PSA alone in screening for prostate cancer as this results in missing 18%–28% cancers.[8]
Although PSA is the most popular biomarker for prostate cancer, it is one of the most controversial issues. A recent study recognized the disadvantage of PSA for the early detection of prostate cancer. It was found that multiple men must be screened, biopsied, and diagnosed to prevent one fatality.[9] False-positive and false-negative results are still common,[10] especially in the so-called “gray zone” (4–10 ng/ml), which represents a dilemma for discriminating PC from BPH, prostatitis, and urethral manipulations which often increase PSA levels.[11] Conversely, there is also a significant number of diagnosed prostate carcinomas with a PSA below 4 ng/ml (estimated at 20%–30%), resulting in undiagnosed disease.[12] Various concepts such as free to total PSA ratio, PSA velocity, PSA density, and age-specific PSA ranges have been introduced, but their clinical significance is still under investigation.[13] Therefore, there is still a great demand for new markers to improve the PC diagnosis and prevent unnecessary prostate biopsies, especially in the serum PSA “gray zone.”
Urine is readily available and can be used to detect either exfoliated cancer cells or secreted products. The major advantages of urine-based assays are their noninvasive character and ability to monitor PC with heterogeneous foci. Using differential display analysis, prostate cancer antigen 3 (PCA3) was first described by Bussemakers et al.[14] in 1999. Prostate tumors showed a 66-fold upregulation of PCA3 in more than 95% of cancer cases compared to benign prostate tissue. The addition of PCA3 to the urologist's diagnostic tools will result in increased diagnostic sensitivity, specificity, and predictive value.
The first prostate gene fusions, untranslated region of TMPRSS2 fused to ERG or ETV1 transcription factors, were discovered by Tomlins et al. in 2005.[15] TMPRSS2 is a type II transmembrane serine protease (21q22.3) expressed in normal prostate epithelium and involved in many physiological and pathological processes, but its exact biological function is still unknown. The urine-based assays can monitor prostate cancer with heterogeneous foci and provide a noninvasive alternative to multiple biopsies. Even if urine assays cannot detect cancers which do not shed tumor cells into urine, it still deserves considerable attention. The combination of multiple urine biomarkers could be of special value in men who have persistently elevated serum PSA and a history of negative biopsies. The emerging biomarkers (ANXA3, sarcosine, gene fusions, PCA3 and others) should help in both early diagnosis of PC and identifying aggressive tumors for radical treatment.[16]
References | |  |
1. | Ghagane SC, Nerli RB, Hiremath MB, Wagh AT, Magdum PV. Incidence of prostate cancer at a single tertiary care center in North Karnataka. Indian J Cancer 2016;53:429-31.  [ PUBMED] [Full text] |
2. | Smith RA, Manassaram-Baptiste D, Brooks D, Doroshenk M, Fedewa S, Saslow D, et al. Cancer screening in the United States, 2015: A review of current American cancer society guidelines and current issues in cancer screening. CA Cancer J Clin 2015;65:30-54. |
3. | Greenberg R. Does prostate cancer represent more than one cancer? In: Mydlo JH, Godec CJ, editors. Prostate Cancer: Science and Clinical Practice. San Diego, CA: Academic Press; 2003. p. 29-34. |
4. | Brawer MK, Chetner MP, Beatie J, Buchner DM, Vessella RL, Lange PH, et al. Screening for prostatic carcinoma with prostate specific antigen. J Urol 1992;147:841-5. |
5. | Ghagane SC, Nerli RB, Hiremath MB, Kaliwal BB. Docetaxel based treatment for metastatic castration-resistant prostate cancer-our early experience. Transl Biomed 2016;2:1-6. |
6. | Crawford ED, DeAntoni EP, Etzioni R, Schaefer VC, Olson RM, Ross CA, et al. Serum prostate-specific antigen and digital rectal examination for early detection of prostate cancer in a national community-based program. The Prostate Cancer Education Council. Urology 1996;47:863-9. |
7. | Mettlin C, Murphy GP, Lee F, Littrup PJ, Chesley A, Babaian R, et al. Characteristics of prostate cancers detected in a multimodality early detection program. The Investigators of the American Cancer Society-National Prostate Cancer Detection Project. Cancer 1993;72:1701-8. |
8. | Babaian RJ, Camps JL. The role of prostate-specific antigen as part of the diagnostic triad and as a guide when to perform a biopsy. Cancer 1991;68:2060-3. |
9. | Stattin P, Vickers AJ, Sjoberg DD, Johansson R, Granfors T, Johansson M, et al. Improving the specificity of screening for lethal prostate cancer using prostate-specific antigen and a panel of kallikrein markers: A Nested case-control study. Eur Urol 2015;68:207-13. |
10. | Freedland SJ, Partin AW. Prostate-specific antigen: Update 2006. Urology 2006;67:458-60. |
11. | Thompson IM, Ankerst DP, Chi C, Lucia MS, Goodman PJ, Crowley JJ, et al. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA 2005;294:66-70. |
12. | Schröder FH, van der Cruijsen-Koeter I, de Koning HJ, Vis AN, Hoedemaeker RF, Kranse R, et al. Prostate cancer detection at low prostate specific antigen. J Urol 2000;163:806-12. |
13. | Shariat SF, Karam JA, Margulis V, Karakiewicz PI. New blood-based biomarkers for the diagnosis, staging and prognosis of prostate cancer. BJU Int 2008;101:675-83. |
14. | Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA, et al. DD3: A new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 1999;59:5975-9. |
15. | Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005;310:644-8. |
16. | Jamaspishvili T, Kral M, Khomeriki I, Student V, Kolar Z, Bouchal J, et al. Urine markers in monitoring for prostate cancer. Prostate Cancer Prostatic Dis 2010;13:12-9. |
|