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In Reply

Department of Medicine, Divison of Hematology/Oncology, Massachusetts General Hospital, Boston, MA

We thank Drs Cai and Bartoletti for their thoughtful comments. We agree that quality of life and survivorship are of paramount importance for men receiving androgen-deprivation therapy (ADT) for nonmetastatic prostate cancer. Recent studies demonstrated that ADT not only decreases bone mineral density (BMD) and increases fracture risk, but also increases fat mass,¹ decreases insulin sensitivity,² and is associated with greater risk for incident diabetes and cardiovascular disease.³

Zoledronic acid (4 mg every 3 weeks) significantly reduces the risk of skeletal-related events, including fractures in men with hormone refractory metastatic prostate cancer.⁴ The efficacy of zoledronic acid or other drugs to prevent fractures in men with hormone-sensitive nonmetastatic prostate cancer has not yet been established. Our recently published randomized controlled trial demonstrated that annual zoledronic acid significantly increases BMD, a surrogate for fracture risk, in men receiving ADT for nonmetastatic prostate cancer.⁵ Ongoing large randomized trials will assess the impact of drug therapy on incident fractures, including pivotal studies of toremifene (a selective estrogen receptor modulator) and denosumab (a human monoclonal antibody targeting receptor activator of nuclear factor–kappaB ligand).⁶ Results of these studies will help to define standards of care. We currently recommend assessment of fracture risk by history, laboratory testing, and measurement of BMD for all men undergoing long-term ADT for nonmetastatic prostate cancer. Pending results of the pivotal fracture prevention studies, we recommend supplemental calcium and vitamin D with selective use of drug therapy for men at greatest fracture risk.

The recent increase in recognition of the adverse effects of ADT emphasizes the importance of weighing both potential benefits and harms when considering hormone therapy in individual men. We recommend similar care in considering interventions to reduce treatment-related adverse effects.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Smith MR, Finkelstein JS, McGovern FJ, et al: Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab 87:599-603, 2002[Abstract/Free Full Text]

2. Smith MR, Lee H, Nathan DM: Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab 91:1305-1308, 2006[Abstract/Free Full Text]

3. Keating NL, O'Malley AJ, Smith MR: Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 24:4448-4456, 2006[Abstract/Free Full Text]

4. Saad F, Gleason DM, Murray R, et al: A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 94:1458-1468, 2002[Abstract/Free Full Text]

5. Michaelson MD, Kaufman DS, Lee H, et al: Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist–induced bone loss in men with prostate cancer. J Clin Oncol 25:1038-1042, 2007[Abstract/Free Full Text]

6. Smith MR: Treatment-related osteoporosis in men with prostate cancer. Clin Cancer Res 12:6315s–6319s, 2006

Related Correspondence

• Patient Quality of Life Safeguarding: The Primary Aim in Nonmetastatic Prostate Cancer Patients
  Tommaso Cai and Riccardo Bartoletti
  JCO 2007 25: 3385 [Full Text]

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