Beyond the Abstract - Chronic prostatitis does not influence urinary PCA3 score, by Vlaminck-Guillem Virginie, MD., PhD.

BERKELEY, CA (UroToday.com) - The urinary PCA3 test is now recognized as a useful adjunct for a prostate biopsy decision in patients with suspicion of prostate cancer [1].

It could be proposed in each situation, in which serum PSA is not accurate enough [1]. Actual indication appears in patients with previous negative biopsies, even if the recent data supports indication enlargement in first-time patients submitted for prostate biopsy [2]. Another situation is a patient with familial history of prostate cancer in whom cancer detection is expected before the discovery of an increased serum PSA [3]. At last, the estimated urinary PCA3 test will be useful in clinical situations in which serum PSA is known to increase because of an underlying benign prostate pathology. Acute prostatitis is a benign prostate pathology, known to induce dramatic and prolonged increases in serum PSA [3]. It has been suggested that the PCA3 score is not affected by acute prostatitis [3,4]. To our knowledge, it has not been specifically evaluated whether chronic prostatitis has similar effects or not. However, published clinical studies assessing diagnostic performances of urinary PCA3 tests are likely to have included patients with prostatitis as part of the control, noncancerous patients. The rare studies that mentioned this fact did not give significant and precise data about this subpopulation of patients [5-7]. It has been suggested that patients with “prostate inflammation” don’t have significantly different PCA3 scores when compared to patients with a histologically normal prostate or benign prostate hyperplasia [8]. The exact nature of prostate inflammation is, nevertheless, unavailable in this study [8]. We, therefore, conducted a specific study to address the question: is PCA3 score affected in 34 patients with documented chronic prostatitis [9]? In this study, patients were classified according to the NIH classification: acute bacterial (type I), chronic bacterial (type II), chronic prostatitis/chronic pelvic pain syndrome (type III a and b), and asymptomatic (type IV) [10]. A simplified version of the Meares-Stamey, 4-glass localization test was performed [11], and urine specimens were collected for cytological analysis and culture. A post-prostatic massage urine sample was used for the urinary PCA3 test. It could then demonstrated that all 34 chronic prostatitis patients had a PCA3 score less than 28; i.e., under the cutoff of 35, which is commonly used for prostate cancer diagnosis [9]. In other words, the PCA3 test can be used to reinforce the opinion that an increase in PSA is related to prostate inflammation rather than prostate cancer if the PCA3 score is low. By contrast, if the urinary PCA3 score is high, a prostate biopsy is needed because it is unlikely that prostate inflammation is responsible for a positive PCA3 test.

As a parallel with prostate inflammation, benign prostate hyperplasia (BPH) can also induce an increase in serum PSA and, therefore, an inaccurate prostate biopsy. Whether BPH alters PCA3 score and/or diagnostic performances of the PCA3 test has been poorly explored in the published literature. Expression studies demonstrated that up to 57% of BPH tissues could express the PCA3 gene [12-15]. Nevertheless, this expression is 5 to 66 fold less than that observed in prostate cancer [6,14-19]. Similar to prostate inflammation, BPH patients are likely to be included as part of the control, non-cancer patients in clinical studies about PCA3 test performances. Only 3 studies specifically compared PCA3 scores in cancer versus BPH patients [20-22]. The median PCA3 scores were higher in cancer patients than BPH patients. PCA3 test capability to distinguish the 2 groups was good, with the area under the ROC curve estimated between 0.68 and 0.814, sensitivity between 60 and 63%, and specificity between 91 and 100%. Another indication that PCA3 score is not altered by the presence of BPH is the fact that, by contrast to serum PSA, it has never correlated with prostate volume [8,23]. Whether the treatment of BPH modifies the PCA3 score or alters its diagnostic performances has also been recently addressed. A first, the study demonstrated that green light laser vaporization for BPH does not prevent diagnostic PCA3 tests [24], while another gave significant results about the long-term use of dutasteride, an inhibitor of 5-alpha-reductase used in symptomatic BPH and in the prevention of prostate cancer [25]. A 4-year treatment with dutasteride did not modify PCA3 scores and did not alter its discriminative properties [25], suggesting that the test can be applied to patients submitted to this treatment.

In conclusion, benign prostatic pathologies can be considered as neutral clinical conditions that do not alter PCA3 scores or the capabilities of the urinary PCA3 test to predict results of the prostate biopsy. As a result, an increase in PCA3 score observed in patients with such conditions cannot be explained by this sole pathology, and requires prostate biopsy. A different conclusion must be drawn for a last “benign” condition identified by prostate biopsy: preneoplastic HGPIN and ASAP Both could be associated with an increase in PCA3 scores, which may induce difficulties for guiding repeat biopsy decisions [23,26], but further studies are needed.

References:

  1. Auprich M, Bjartell A, Chun FK, de la Taille A, Freedland SJ, Haese A, et al. Contemporary role of prostate cancer antigen 3 in the management of prostate cancer. Eur Urol. 201;60:1045-1054.
  2. de la Taille A, Irani J, Graefen M, Chun F, de Reijke T, Kil P, et al. Clinical evaluation of the PCA3 assay in guiding initial biopsy decisions. J Urol. 2011;185:2119-2125.
  3. Marks LS, Bostwick DG. Prostate Cancer Specificity of PCA3 Gene Testing: Examples from Clinical Practice. Rev Urol. 2008;10:175-181.
  4. Marks L, Weber A, Rittenhouse H, Macairan ML, Yee S, Bostwick D. Effects of prostatitis on serum PSA and urinary PCA3 gene score. J Urol. 2010;183:314.a
  5. Groskopf J, Aubin SM, Deras IL, Blase A, Bodrug S, Clark C, et al. APTIMA PCA3 molecular urine test: development of a method to aid in the diagnosis of prostate cancer. Clin Chem. 2006;52:1089-1095.
  6. Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, van Balken B, et al. DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur Urol. 2003;44:8-15.
  7. Tinzl M, Marberger M, Horvath S, Chypre C. DD3PCA3 RNA analysis in urine—a new perspective for detecting prostate cancer. Eur Urol. 2004;46:182-186.
  8. Deras IL, Aubin SM, Blase A, Day JR, Koo S, Partin AW, et al. PCA3: a molecular urine assay for predicting prostate biopsy outcome. J Urol. 2008;179:1587-1592.
  9. Vlaeminck-Guillem V, Bandel M, Cottancin M, Rodriguez-Lafrasse C, Bohbot JM, Sednaoui P. Chronic prostatitis does not influence urinary PCA3 score. Prostate. Published 2011. Accessed 2011.
  10. Habermacher GM, Chason JT, Schaeffer AJ. Prostatitis/chronic pelvic pain syndrome. Annu Rev Med. 2006;57:195-206.
  11. Meares EM, Stamey TA. Bacteriologic localization patterns in bacterial prostatitis and urethritis. Invest Urol. 1968;5:492-518.
  12. Bialkowska-Hobrzanska H, Driman DK, Fletcher R, Harry V, Razvi H. Expression of human telomerase reverse transcriptase, Survivin, DD3 and PCGEM1 messenger RNA in archival prostate carcinoma tissue. Can J Urol. 2006;13:2967-2974.
  13. Clarke RA, Zhao Z, Guo AY, Roper K, Teng L, Fang ZM, et al. New genomic structure for prostate cancer specific gene PCA3 within BMCC1: implications for prostate cancer detection and progression. PLoS One. 2009;4:4995.
  14. Neves AF, Araujo TG, Biase WK, Meola J, Alcantara TM, Freitas DG, Goulart LR. Combined analysis of multiple mRNA markers by RT-PCR assay for prostate cancer diagnosis. Clin Biochem. 2008;41:1191-1198.
  15. Tao Z, Shen M, Zheng Y, Mao X, Chen Z, Yin Y, et al. PCA3 gene expression in prostate cancer tissue in a Chinese population: quantification by real-time FQ-RT-PCR based on exon 3 of PCA3. Exp Mol Pathol. 2010;89:58-62.
  16. de Kok JB, Verhaegh GW, Roelofs RW, Hessels D, Kiemeney LA, Aalders TW, et al. DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res. 2002;62:2695-2698.
  17. Floriano-Sanchez E, Cardenas-Rodriguez N, Castro-Marin M, Alvarez-Grave P, Lara-Padilla E. DD3(PCA3) gene expression in cancer and prostatic hyperplasia. Clin Invest Med. 2009;32:258.
  18. Klecka J, Holubec L, Pesta M, Topolcan O, Hora M, Eret V, et al. Differential display code 3 (DD3/PCA3) in prostate cancer diagnosis. Anticancer Res. 2010;30:665-670.
  19. Landers KA, Burger MJ, Tebay MA, Purdie DM, Scells B, Samaratunga H, et al. Use of multiple biomarkers for a molecular diagnosis of prostate cancer. Int J Cancer. 2005;114:950-956.
  20. Mearini E, Antognelli C, Del Buono C, Cochetti G, Giannantoni A, Nardelli E, et al. The combination of urine DD3(PCA3) mRNA and PSA mRNA as molecular markers of prostate cancer. Biomarkers. 2009;14:235-243.
  21. Shen M, Chen W, Yu K, Chen Z, Zhou W, Lin X, et al. The diagnostic value of PCA3 gene-based analysis of urine sediments after digital rectal examination for prostate cancer in a Chinese population. Exp Mol Pathol. 2011;90:97-100.
  22. Talesa VN, Antognelli C, Del Buono C, Stracci F, Serva MR, Cottini E, et al. Diagnostic potential in prostate cancer of a panel of urinary molecular tumor markers. Cancer Biomark. 2009;5:241-51.
  23. Haese A, de la Taille A, van Poppel H, Marberger M, Stenzl A, Mulders PF, et al. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur Urol. 2008;54:1081-1088.
  24. Henderson J, Ghani KR, Cook J, Fahey M, Schalken J, Thilagarajah R. The role of PCA3 testing in patients with a raised prostate-specific antigen level after Greenlight photoselective vaporization of the prostate. J Endourol. 2010;24:1821-1824.
  25. Aubin SM, Reid J, Sarno MJ, Blase A, Aussie J, Rittenhouse H, et al. Prostate Cancer Gene 3 Score Predicts Prostate Biopsy Outcome in Men Receiving Dutasteride for Prevention of Prostate Cancer: Results From the REDUCE Trial. Urology. 2011;78:380-385.
  26. Morote J, Rigau M, Garcia M, Mir C, Ballesteros C, Planas J, et al. Behavior of the PCA3 gene in the urine of men with high grade prostatic intraepithelial neoplasia. World J Urol. 2010;28:677-80.

Written by:
Vlaminck-Guillem Virginie, MD., PhD.,1 as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

1Service de Biochimie Biologie Moléculaire Sud, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Chemin du Grand Revoyet, 69495, Pierre Bénite cedex, France ().

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