Prospective determination of the hormonal response after cessation of luteinizing hormone-releasing hormone agonist treatment in patients with prostate cancer

Objectives. To determine the hormonal (luteinizing hormone [LH] and testost erone) and biochemical (serum prostate-specific antigen [PSA]) response to withdrawal of luteinizing hormone-releasing hormone (LHRH) agonists in pati ents who received more than 2 years of LHRH therapy for advanced prostate c ancer. Methods. Fourteen patients with clinical Stage T3 or higher prostate cancer and no evidence of clinical or biochemical progression, who had received 2 years or more of LHRH therapy, were enrolled at the time of their schedule d 3-month depot injection. Patients underwent history, physical examination , and measurement of serum PSA, LH, and testosterone at baseline, monthly f or 3 months, and then every 3 months for year following LHRH withdrawal. Results. The mean age of patients was 70.3 years (range 56 to 84). Patients previously received LHRH agonist for a mean of 38.6 months (range 25 to 82 ). All patients had castrate levels of testosterone (median 10.0 ng/dL) and suppressed LH levels (median 0.1 mIU/mL) at baseline. Median baseline PSA was 0.15 ng/mL. On multiple groupwise comparison, there was no significant change (compared with baseline) in LH or testosterone until 6 months after withdrawal and no change in PSA throughout the duration of the study (media n PSA at 12 months 0.30 ng/mL). Despite significant increases in LH and tes tosterone when compared with baseline beginning at 6 months, both LH and te stosterone remained markedly suppressed, with median testosterone remaining in the castrate range at both 6 and 9 months and significantly below the l ower limit of normal at 12 months (median 111.0 ng/dL). Despite no statisti cally significant change for the entire cohort in serum PSA, a rising PSA w as noted in 4 patients between 3 and 9 months, and LHRH therapy was reiniti ated. The remaining patients continued to have suppressed LH and testostero ne, with 4 patients remaining in the castrate range at 12 months. Conclusions. The recovery of function of the hypothalamic-pituitary-testicu lar axis after prolonged LHRH administration is variable. Castrate levels o f testosterone and suppressed LH may persist even up to 1 year after discon tinuing LHRH. These results have significant implications regarding the int erpretation of clinical trials incorporating neoadjuvant and adjuvant hormo nal therapy. Further studies are needed to expand on these preliminary obse rvations and should also address the feasibility of incorporating LHRH with drawal into clinical practice. UROLOGY 53: 898-903, 1999. (C) 1999, Elsevie r Science Inc. All rights reserved.