Purpose: The study aims to investigate the potential associations between preoperative plasma levels of total testosterone (TT) and biopsy Gleason score (bGS) upgrading in prostate cancer (PCA) patients undergoing radical prostatectomy (RP). Materials and Methods: Exclusion criteria were treatment with 5α-reductase inhibitors, LH-releasing hormone analogues or testosterone replacement. Criteria of bGS upgrading were as follows: (i) bGS 6 to pathological Gleason score (pGS) >6, (ii) bGS 7 with pattern 3 + 4 to pGS 7 with pattern 4 + 3 or to pGS >7, (iii) bGS 7 with pattern 4 + 3 to pGS >7. Patients who showed bGS >7 were excluded from the cohort. Results: The study included 209 patients. Tumor upgrading was assessed in 76 (36.4%) cases of the entire cohort, in 51 out of 130 cases (39.2%) of the bGS 6 group and 25 out of 79 patients (31.6%) in the bGS 7 cluster. Logistic regression models showed that independent clinical covariates predicting the risk of bGS upgrading included TT (OR 1.058; p = 0.027) and prostate-specific antigen (PSA) density (OR 23.3; p = 0.008) as well as TT (OR 1.057; p = 0.029) with PSA (OR 1.061; p = 0.023). The model suggests that 1 unit increase in TT plasma levels increases the odds of bGS upgrading by 5.8 or 5.7%. Conclusions: In summary, we have determined that high TT preoperative plasma levels independently predict bGS upgrading in men with PCA undergoing RP. Preoperative plasma levels of TT might be included as a potential marker for assessing the risk bGS upgrading.

1.
Huggins C, Hodges CV: Studies on prostate cancer. I: the effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941;1:293-297.
2.
Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E: Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987;317:909-916.
3.
Armbruster DA: Prostate-specific antigen: biochemistry, analytical methods, and clinical application. Clin Chem 1993;39:181-195.
4.
Miller LR, Partin AW, Chan DW, Bruzek DJ, Dobs AS, Epstein JI, Walsh PC: Influence of radical prostatectomy on serum hormone levels. J Urol 1998;160:449-453.
5.
Olsson M, Ekström L, Schulze J, Kjellman A, Akre O, Rane A, Gustafsson O: Radical prostatectomy: influence on serum and urinary androgen levels. Prostate 2010;70:200-205.
6.
Harper ME, Pierrepoint CG, Griffiths K: Carcinoma of the prostate: relationship of pretreatment hormone levels to survival. Eur J Cancer Clin Oncol 1984;20:477-482.
7.
Chen SS, Chen KK, Lin AT, Chang YH, Wu HH, Chang LS: The correlation between pretreatment serum hormone levels and treatment outcome for patients with prostatic cancer and bony metastasis. BJU Int 2002;89:710-713.
8.
Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC: Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999;281:1591-1597.
9.
Hull GW, Rabbani F, Abbas F, Wheeler TM, Kattan MW, Scardino PT: Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urol 2002;167(2 pt 1):528-534.
10.
Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, Partin AW: Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA 2005;294:433-439.
11.
Cuzick J, Fisher G, Kattan MW, Berney D, Oliver T, Foster CS, Møller H, Reuter V, Fearn P, Eastham J, Scardino P; Transatlantic Prostate Group: Long-term outcome among men with conservatively treated localised prostate cancer. Br J Cancer 2006;95:1186-1194.
12.
Tilki D, Schlenker B, John M, et al: Clinical and pathologic predictors of Gleason sum upgrading in patients after radical prostatectomy: result from a single institution series. Urol Oncol 2011;29:508-514.
13.
Isariyawongse BK, Sun L, Bañez LL, et al: Significant discrepancies between diagnostic and pathologic Gleason sums in prostate cancer: the predictive role of age and prostate-specific antigen. Urology 2008;72:882-886.
14.
Chun FK, Briganti A, Shariat SF, et al: Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation. BJU Int 2006;98:329-334.
15.
Kulkarni GS, Lockwood G, Evans A, et al: Clinical predictors of Gleason score upgrading: implications for patients considering watchful waiting, active surveillance, or brachytherapy. Cancer 2007;109:2432-2438.
16.
Klap J, Schmid M, Loughlin KR: The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy. J Urol 2015;193:403-413.
17.
Porcaro AB, Petrozziello A, Ghimenton C, Migliorini F, Sava T, Caruso B, Cocco C, Romano M, Cavalleri S, Artibani W: Serum total testosterone is a significant preoperative variable independently contributing to separating the prostate cancer population into prostatectomy Gleason score groups. Urol Int 2013;91:55-61.
18.
Porcaro AB, Petrozziello A, Ghimenton C, Migliorini F, Sava T, Caruso B, Romano M, Cavalleri S, Artibani W: Associations of pretreatment serum total testosterone measurements with pathology-detected Gleason score cancer. Urol Int 2014;93:269-278.
19.
Corcoran NM, Casey RG, Hong MK, Pedersen J, Connolly S, Peters J, Harewood L, Gleave ME, Costello AJ, Hovens CM, Goldenberg SL: The ability of prostate-specific antigen (PSA) density to predict an upgrade in Gleason score between initial prostate biopsy and prostatectomy diminishes with increasing tumour grade due to reduced PSA secretion per unit tumour volume. BJU Int 2011;110:36-42.
20.
Schiffmann J, Wenzel P, Salomon G, et al: Heterogeneity in D'Amico classification-based low-risk prostate cancer: differences in upgrading and upstaging according to active surveillance eligibility. Urol Oncol 2015;33:329.e13-e19.
21.
El Hajj A, Ploussard G, de la Taille A, et al: Analysis of outcomes after radical prostatectomy in patients eligible for active surveillance (PRIAS). BJU Int 2013;111:53-59.
22.
Berglund RK, Masterson TA, Vora KC, et al: Pathological upgrading and up staging with immediate repeat biopsy in patients eligible for active surveillance. J Urol 2008;180:1964-1968.
23.
San Francisco IF, Rojas PA, DeWolf WC, et al: Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance. BJU Int 2014;114:229-235.
24.
Hyde Z, Flicker L, McCaul KA, et al: Associations between testosterone levels and incident prostate, lung, and colorectal cancer. A population-based study. Cancer Epidemiol Biomarkers Prev 2012;21:1319-1329.
25.
Albisinni S, De Nunzio C, Tubaro A, et al: Greater percent-free testosterone is associated with high-grade prostate cancer in men undergoing prostate biopsy. Urology 2012;80:162-168.
26.
Pierorazio PM, Ferrucci L, Kettermann A, et al: Serum testosterone is associated with aggressive prostate cancer in older men: results from the Baltimore longitudinal study of aging. BJU Int 2010;105:824-829.
27.
McNeal JE, Bostwick DG, Kindrachuk RA, Redwine EA, Freiha FS, Stamey TA: Patterns of progression in prostate cancer. Lancet 1986;1:60-63.
28.
Nelson PS: Molecular states underlying androgen receptor activation: a framework for therapeutics targeting androgen signaling in prostate cancer. J Clin Oncol 2012;30:644-646.
29.
Epstein JI, Egevad L, et al: The 2014 international society of urological pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol 2016;40:244-252.
30.
Park J, Cho SY, Jeong SH, et al: Low testosterone level is an independent risk factor for high-grade prostate cancer detection at biopsy. BJU Int 2015, Epub ahead of print.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.