Purpose: With stage migration induced by early diagnosis of prostate-specific antigen, the course of disease for prostate cancer (PCa) patients has changed. Increasingly, patients undergo long-term androgen ablation with consecutive risks including osteoporosis and pathologic fractures. A recent randomized trial found that the RANK ligand inhibitor denosumab was more effective preventing skeletal-related events in patients with metastatic PCa as compared to treatment with the bisphosphonate zoledronic acid. This improved efficacy was linked to an increase of side effects. Methods: The present analysis compares results reported for both substances using a number needed to treat analysis approach. Based upon these findings, risk-benefit calculations were performed. Results: The results demonstrate that for patients with bone metastatic castration-resistant PCa, decision for or against treatment with either denosumab or zoledronic acid must not only consider efficacy but needs to balance the desired effects versus potential side effects. This is of specific relevance since life expectancy is limited in this patient cohort with end-stage disease. Conclusions: Further scientific efforts are necessary to identify optimal dosing and application intervals for denosumab and zoledronic acid as well as to answer the question of optimal duration of treatment. These findings will directly impact the risk versus benefit relations for both therapeutic options.

1.
Thompson IM, Ankerst DP: Prostate-specific antigen in the early detection of prostate cancer. CMAJ 2007;176:1853-1858.
2.
Ward JF, Moul JW: Biochemical recurrence after definitive prostate cancer therapy. II. Treatment strategies for biochemical recurrence of prostate cancer. Curr Opin Urol 2005;15:187-195.
3.
Morote J, Martinez E, Trilla E, Esquena S, Abascal JM, Encabo G, Reventós J: Osteoporosis during continuous androgen deprivation: influence of the modality and length of treatment. Eur Urol 2003;44:661-665.
4.
Malcolm JB, Derweesh IH, Kincade MC, DiBlasio CJ, Lamar KD, Wake RW, Patterson AL: Osteoporosis and fractures after androgen deprivation initiation for prostate cancer. Can J Urol 2007;14:3551-3559.
5.
Daniell HW: Osteoporosis after orchiectomy for prostate cancer. J Urol 1997;157:439-444.
6.
Abrahamsen B, Nielsen MF, Eskildsen P, Andersen JT, Walter S, Brixen K: Fracture risk in Danish men with prostate cancer: a nationwide register study. BJU Int 2007;100:749-754.
7.
Saad F, Gleason DM, Murray R, Tchekmed-yian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Zheng M, Zoledronic Acid Prostate Cancer Study Group: Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004;96:879-882.
8.
Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C: Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011;377:813-822.
9.
Laupacis A, Sackett DL, Roberts RS: An assessment of clinically useful measures of the consequences of treatment. N Engl J Med 1988;318:1728-1733.
10.
Sur RL, Scales CD Jr, Preminger GM, Dahm P: Evidence-based medicine: a survey of American Urological Association members. J Urol 2006;176:1127-1134.
11.
Common Terminology Criteria for Adverse Events Classification Version 4.0: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.
12.
Breau RH, Fergusson D, Dahm P: Evidence-based urology in practice: number needed to treat. BJU Int 2009;104:6-8.
13.
Miller K, Fizazi K, Smith M, Morote JP, Klotz L, Brown J, Tammela TLJ, Shore N, Ke C, Chung K, Goessl C: Benefit of denosumab therapy in patients with bone metastases from castrate resistant prostate cancer: a number-needed-to-treat (NNT) analysis. 109th Meeting of the American Urological Association, Washington, 2011, A648.
14.
Xie J, Namjoshi M, Wu EQ, Parikh K, Diener M, Yu AP, Guo A, Culver KW: Economic evaluation of denosumab compared with zoledronic acid in hormone-refractory prostate cancer patients with bone metastases. J Manag Care Pharm 2011;17:621-643.
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.