Luteinizing Hormone-releasing Hormone Agonist Monotherapy Research Articles

Combined androgen blockade (CAB) versus luteinizing hormone-releasing hormone (LHRH) agonist monotherapy for androgen deprivation therapy

Combined androgen blockade (CAB) and luteinizing hormone-releasing hormone (LHRH) agonist monotherapy are commonly used in androgen deprivation therapy (ADT). In this randomized clinical trial, we aimed to compare the two methods of ADT in terms of quality of life (QOL). Eighty patients who underwent primary ADT for newly diagnosed prostate cancer were randomly assigned to CAB group (Group 1) and LHRH agonist monotherapy group (Group 2). Leuprolide and anti-androgen (bicalutamide 50mg) were used to minimize the confounding effects caused by medication. QOL was evaluated at baseline, 3months and 6months post-ADT using validated EORTC QLQ-C30, PR25, and depression questionnaires. A difference of > 10 points in the EORTC domain scores was defined as 'clinically significant'. In the baseline characteristics, there was no significant difference between the two groups. At 3months after ADT, Group 1 had significantly lower pain scores than Group 2 (p = 0.004), while Group 1 had significantly poorer diarrhea symptom score than Group 2, without clinical significance (p = 0.047). No significant differences were observed in the C30, PR25 domains, and the depression score at 3months. At 6months, the QOL scores of all the groups were similar. There was no difference in the patient's QOL, except that CAB group was associated with significantly better pain relief than LHRH agonist monotherapy at 3months following ADT, which was not sustained thereafter. Our results suggest that the benefit of prolonged (≥ 3months) CAB is questionable in terms of patients' QOL.

Effects of a luteinizing hormone-releasing hormone agonist on cognitive, sexual, and hormonal functions in patients with prostate cancer: relationship with testicular and adrenal androgen levels.

PurposeTo assess the cognitive and sexual/hormonal functioning of prostate cancer patients treated with a luteinizing hormone-releasing hormone (LH-RH) agonist, and the relationships thereof with adrenal and residual testicular androgen levels.Materials and methodsPreviously, we reported the effect of a luteinizing hormone-releasing hormone (LH-RH) agonist on testicular and adrenal androgen production in patients with prostate cancer. A 6-month treatment with an LH-RH agonist significantly reduced testicular androgens by 90–95% and adrenal androgens by 26–40%. This study evaluated the changes in cognitive and sexual/hormonal functions in the same cohort using the Mini-Mental State Evaluation (MMSE) and Expanded Prostate Cancer Index Composite (EPIC) questionnaire, respectively. In addition, the associations of each function with the serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), dehydroepiandrosterone-sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione (A-dione), and cortisol levels were studied.ResultsCognitive functions did not change significantly during the treatment. Sexual functions were relatively low before treatment and worsened significantly after 6 and 12 months of treatment. Interestingly, sexual bothers were improved with the treatment. The treatment significantly worsened hormonal functions and bothers. Regarding specific items in the hormonal domains, hot flashes and body weight changes were the main effects of worsened hormonal function. Low levels of T and E2 and high levels of A-dione were associated with low MMSE scores at 6 months. Regarding sexual and hormonal functions, A-dione, E2, T, cortisol, and DHEA-S were associated with poorer functioning and bother. Especially, low T levels and high E2 levels were the most significant factors associated with worse sexual and hormonal bothers.ConclusionThe LH-RH agonist monotherapy worsened sexual and hormonal functions and hormonal bothers, but not sexual bothers or cognitive functions. The changes in these functions were related to the testicular and adrenal androgens levels.

Neoadjuvant Hormone Therapy for Radical Prostate Radiotherapy: Bicalutamide Monotherapy vs. Luteinizing Hormone–Releasing Hormone Agonist Monotherapy: A Single-Institution Matched-Pair Analysis

BackgroundThe purpose of this study was to compare the prostate-specific antigen (PSA) response to either neoadjuvant bicalutamide (BC) monotherapy or neoadjuvant luteinizing hormone–releasing hormone agonist (LHRHa) monotherapy and the subsequent effect on biochemical failure–free survival (BFFS) in men receiving radical radiotherapy (RT) for localized prostate cancer. Patients and MethodsThis was a retrospective review of consecutive men treated with BC monotherapy before radical prostate RT who were individually case-matched to men treated with neoadjuvant LHRHa monotherapy. PSA kinetics and absolute pre-RT posthormone PSA (PRPH-PSA) level and subsequent BFFS were analyzed. ResultsSixty-five men treated with BC monotherapy with a median follow-up of 44 months were individually matched with 65 men treated with LHRHa with a median follow-up of 54 months. Statistically significant differences were noted between groups in the PRPH-PSA, with a mean of 2.9 ng/mL (0.1-11.2 ng/mL) for patients receiving BC treatment and 1.8 ng/mL (0.1-11.1 ng/mL) for patients receiving LHRHa treatment (P < .001). A PRPH-PSA of < 1.0 and < 0.1 ng/mL was seen in 16 (24.6%) and 2 (3%) of the patients receiving BC and 34 (52.3%) and 3 (4.6%) patients receiving LHRHa, respectively. There were no significant differences between groups in either PSA halving time or velocity. Phoenix biochemical failure occurred in 10 (15.4%) and 8 (12.3%) patients receiving BC and patients receiving LHRHa, respectively. Neither PRPH-PSA level nor PSA kinetics during the neoadjuvant period predict for subsequent BFFS at this duration of follow-up. ConclusionsAlthough neoadjuvant BC therapy did not result in equivalent PRPH-PSA suppression when compared with neoadjuvant LHRHa alone, there was no difference in biochemical failure rates between cohorts at 50 months' median follow-up. Longer follow-up is required.

The Long-term Results with Delayed-combined Androgen Blockade Therapy in Local or Locally Advanced Prostate Cancer

To evaluate long-term clinical outcomes in cT1c-T3a prostate cancer patients following delayed-combined androgen blockade therapy. From January 2001 to December 2004, 92 cT1c-T3a prostate cancer cases were enrolled. Medical castration and anti-androgen treatment were used sequentially as delayed-combined androgen blockade therapy. Time to prostate-specific antigen biochemical failure was estimated, and risk factors for prostate-specific antigen biochemical failure were evaluated. The average patient age was 76.4 years (range, 59-91 years), the median observation period was 52.8 months (range, 26-106.6 months) and the median pre-treatment prostate-specific antigen level was 14 ng/ml (range, 3.68-492 ng/ml). The TNM classification distribution was as follows: T1c, n= 27; T2a, n = 39; T2b, n = 20; and T3a, n = 6. In the multivariate analysis, Gleason's score ≥8 (P < 0.05; hazard ratio, 3.02), prostate-specific antigen nadir >1.4 ng/ml (P = 0.001; hazard ratio, 8.76) and a half-life of the prostate-specific antigen level >1.2 months (P < 0.005; hazard ratio, 6.3) during the initial 6 months of luteinizing hormone-releasing hormone agonist monotherapy were significant independent risk factors for prostate-specific antigen biochemical failure with luteinizing hormone-releasing hormone agonist monotherapy. The high-risk group, which had at least one of these three risk factors, had a shorter time to prostate-specific antigen biochemical failure than the low-risk group, during luteinizing hormone-releasing hormone agonist monotherapy (P < 0.0001). For the total delayed-combined androgen blockade therapy observation period, the free-prostate-specific antigen biochemical failure rate was 88.3% at 5 years. Only a maintenance period following luteinizing hormone-releasing hormone agonist monotherapy (P < 0.005; hazard ratio, 16.8) was revealed to be a significant independent risk factor for prostate-specific antigen biochemical failure with total delayed-combined androgen blockade. The free-prostate-specific antigen biochemical failure rate of delayed-combined androgen blockade therapy in our study was as valuable as those in other androgen deprivation therapy of previous reports.

Guidelines for the management of castrate-resistant prostate cancer.

Secondary hormonal manipulations In patients who develop CRPC and who are relatively asymptomatic, secondary hormonal treatments may be attempted. Level 2 Evidence, Grade C recommendation To date, no study of secondary hormone treatment has demonstrated benefits in terms of survival, but most trials have been smaller and heavily confounded by the future treatments used. In patients treated with luteinizing-hormonereleasing hormone agonist monotherapy or who have had an orchidectomy, total androgen blockade (TAB) with testosterone antagonists, such as bicalutamide, can offer PSA responses in 30% to 35% of patients. For patients who progress on ADT without evidence of distant metastases, it is suggested to screen them for bone metastases and to monitor them for visceral metastases/progression with abdomen and chest imaging. Exact timing of imaging may be modulated using PSA doubling time. Imaging techniques most commonly used include nuclear bone scans and abdominal computed tomography and chest X-ray. The role of magnetic resonance imaging and positron emission tomography is still unclear. For patients who have undergone TAB, the antiandrogen could be discontinued to exclude an antiandrogen withdrawal response (AAWD). The introduction or changes of an AA or the use of ketoconazole has been reported to have transient PSA reductions in about 30% of patients. 3 Level

Combined androgen blockade with bicalutamide for advanced prostate cancer

A previously reported, double-blind, randomized, multicenter phase 3 trial in 205 patients with stage C/D prostate cancer compared combined androgen blockade (CAB) with luteinizing hormone-releasing hormone agonist (LHRH-A) plus bicalutamide 80 mg versus LHRH-A plus bicalutamide-matching placebo (LHRH-A monotherapy). The analysis at a median follow-up of 2.4 years indicated that CAB significantly (P<.001) prolonged the time to progression and the time to treatment failure. In the current report, survival data from a long-term follow-up (median, 5.2 years) were analyzed. All deaths irrespective of cause and all prostate cancer-specific deaths were recorded. The data were analyzed using Cox regression analysis and the log-rank test. At a median follow-up of 5.2 years, a significant overall survival advantage was observed in favor of CAB over LHRH-A monotherapy (Cox regression analysis: hazard ratio, 0.78; 95% confidence interval, 0.60-0.99; P=.0498; log-rank test: P=.0425). The difference in cause-specific survival between the 2 groups was not significant. The achievement of a prostate-specific antigen (PSA) nadir concentration<or=1 ng/mL was a prognostic factor for improved survival. More patients attained PSA nadir concentrations<or=1 ng/mL with CAB compared with patients who received LHRH-A monotherapy (81.4% vs 33.7%; P<.001). CAB with bicalutamide 80 mg offered a significant overall survival benefit compared with LHRH-A monotherapy without reducing tolerability in patients with locally advanced or metastatic prostate cancer.

Extended analyses: Combined androgen blockade (CAB) therapy with bicalutamide vs. luteinizing hormone-releasing hormone agonist (LHRHa) monotherapy in Japanese men with untreated advanced prostate cancer

5063 Background: Phase III trial (PIII) results of first-line CAB (bicalutamide 80 mg [licensed dose in Japan] plus LHRHa) for Japanese men with advanced prostate cancer (PC) were shown to be significantly better than LHRHa monotherapy in TTP and TTTF without reduced tolerability, and achieve earlier QOL improvement. This report was cited in the 2007 Update of ASCO Practice Guideline Recommendations. PSA was also decreased significantly faster and lower with CAB than LHRHa alone. The PIII showed no difference in overall survival (OS) between the groups because of lack of events, but a long-term follow-up of PIII conducted by CABPC Study did indicate a significant OS benefit for CAB over LHRHa alone. Here we present the final analyses of this long-term follow-up study. Methods: Five-year survival rates for 203 Japanese men with advanced PC in the original study (CAB=102, LHRHa alone=101) were calculated (Kaplan- Meier method), and OS, cause-specific survival (CSS) and OS by PSA nadir were analyzed by use of Cox regression (HR) and log-rank test. Results: Both groups were demographically similar. At the 270 weeks median follow-up, there were 26 deaths in the CAB and 38 in the LHRHa alone. OS for the CAB group was significantly better than for LHRHa alone p=0.0425. Five-year survival rates for CAB and LHRHa alone were 75.3% and 63.4% respectively. CSS was higher with CAB, but the difference was not statistically significant. OS by PSA nadir ≤1 ng/mL was significantly better than for those >1 ng/mL (p<0.0001). Conclusions: For Japanese men with advanced PC, long-term follow-up data had shown a significant OS benefit for CAB with bicalutamide compared with LHRHa monotherapy; and exploratory data suggesting that lowering PSA may be prognostic for OS. In this study, antiandrogens were added to most men with disease progression in the LHRHa alone (response rate 78%, median duration of response 40wks); most with progression in the CAB were observed for AWS (AWS rate 39%, median duration of AWS 58wks). So this result suggests that immediate CAB prolongs survival better than deferred CAB. No significant financial relationships to disclose.

Evaluation of quality of life in patients with previously untreated advanced prostate cancer receiving maximum androgen blockade therapy or LHRHa monotherapy: a multicenter, randomized, double-blind, comparative study

To assess quality of life (QOL) data from a double-blind Phase III study evaluating bicalutamide (Casodex) 80 mg as part of maximum androgen blockade (MAB) in patients with previously untreated advanced prostate cancer. Patients with untreated stage C/D prostate cancer were randomized to MAB with bicalutamide plus a luteinizing hormone-releasing hormone agonist (LHRHa) or LHRHa monotherapy. QOL was evaluated at baseline and at weeks 1, 5, and 24 using the Japanese version of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. A total of 203 patients were assessed for QOL. The MAB group had more rapid and greater improvements in "emotional well-being" and "prostate cancer-specific issues" domain scores than the monotherapy group. Further analysis of "prostate cancer-specific issues" revealed that, compared with monotherapy, MAB provided a greater improvement in "micturition disorder"-related QOL. Complete improvement rates for items related to "pain and micturition disorder" were also higher with MAB. Item scores of "pain and micturition disorder" did not correlate strongly with prostate-specific antigen levels or tumor size. Fewer patients who had deterioration in their "pain and micturition disorder" item scores at week 1 in the MAB group than the monotherapy group. Maximum androgen blockade with bicalutamide plus LHRHa did not reduce the overall QOL of patients with previously untreated advanced prostate cancer. MAB was superior to monotherapy in achieving early improvement of QOL related to micturition disorder and pain.

Concomitant and adjuvant androgen deprivation (ADT) with external beam irradiation (RT) for locally advanced prostate cancer: 6 months versus 3 years ADT—Results of the randomized EORTC Phase III trial 22961

5014 Background: After EORTC trial 22863, 3 years of endocrine treatment has become standard adjuvant treatment to RT for locally advanced prostate cancer. EORTC 22961 tests if similar survival can be achieved in patients who underwent EBRT (to 70 Gy) and 6 months of combined ADT without further ADT (SADT arm) as in patients with 2.5 years of further treatment with luteinizing hormone-releasing hormone agonist monotherapy (LADT arm). Methods: Eligible patients had T1c-2b N1–2 or pN1–2, or T2c-4 N0–2 (UICC 1992) M0 prostate cancer with PSA &lt;150ng/ml. Non-inferior survival was defined as a morality hazard ratio (HR) = 1.35 for SADT vs LADT. Non inferiority at 80% power and 1-sided a=0.05 required 275 deaths. A stopping boundary was applied at 1-sided a=0.018. Results: 970 patients were randomized (483 SADT and 487 LADT). At 5.2 years median follow-up, 173 patients had died (100 vs 73). An Independent Data Monitoring Committee recommended disclosure of results based on an interim analysis showing futility. Patient characteristics were well balanced: median age 69 years, WHO PS 0 in 83.4%, most patients had T2c-T3 N0 disease. Progression (mostly biochemical and/or bone progression) occurred in 220 cases (159 on SADT vs 61 on LADT) and was treated by secondary hormonal manipulation. The 5-year overall survival rate was 85.3% on LADT and 80.6% on SADT (HR=1.43, 96.4% CI: 1.04–1.98), and failed to prove non-inferiority. The 5-year clinical progression-free survival rate was 81.8% on LADT versus 68.9% on SADT arm and the 5-year biochemical progression-free survival rate was 78.3% on LADT versus 58.9% on SADT, indicating inferiority of SADT with HR=1.93 and HR=2.29, respectively. Conclusions: The study was designed to demonstrate non-inferior survival with 6 months ADT compared to 3 years adjuvant ADT after irradiation for patients with locally advanced prostate cancer, but observed survival data indicate that non-inferiority cannot be confirmed. Progression-free survival was also shorter on SADT. No significant financial relationships to disclose.

Bicalutamide 80 mg combined with a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A monotherapy in advanced prostate cancer: findings from a phase III randomized, double-blind, multicenter trial in Japanese patients

To compare combination therapy with bicalutamide 80 mg and a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A alone in Japanese men with untreated advanced prostate cancer. A total of 205 patients with stage C/D prostate cancer were randomized to either LHRH-A+once-daily oral bicalutamide 80 mg or placebo. Primary study variables have been reported previously. Secondary variables included: time to achieve prostate-specific antigen < or = 4 ng/ml, time-to-treatment failure (TTTF), time-to-disease progression (TTP), overall survival (OS), adverse events and adverse drug reactions. Following combination therapy with bicalutamide 80 mg, there were significant (P<0.001) advantages over LHRH-A alone in terms of TTTF and TTP, but the difference in the interim OS was not statistically significant. First-line combination therapy with bicalutamide 80 mg in Japanese patients with advanced prostate cancer offers significant benefits over LHRH-A alone, with respect to TTTF and TTP. Follow-up for OS continues.

INTERMITTENT ANDROGEN SUPPRESSION IN THE TREATMENT OF PROSTATE CANCER: AN UPDATE OF THE VANCOUVER EXPERIENCE.

Objective Intermittent androgen suppression (IAS) is a feasible treatment for advanced prostate cancer (CaP). We review the long-term follow-up of an IAS cohort. Methods 106 men with a median age of 65.7 years (48.8-86.9) were identified who had been commenced on IAS. At IAS commencement, 16 patients had metastatic disease (MD, lymph node positive or positive bone scan) and 90 had localized disease (LD). Luteinizing hormone-releasing hormone agonist monotherapy was given every 1 to 4 months. A treatment cycle is defined as the time between the initiation of medical castration to the time point of the start of the next treatment phase. Treatment was resumed when the serum PSA increased to an arbitrarily chosen value. Cycles were continued until tumor progression to androgen independence (AI) or treatment was changed to continuous androgen suppression due to patient choice. Results The median follow-up for patients presenting with MD and LD was 47 (12-129) and 43 months (9-126), respectively. The median cycle length and median time off therapy were 20 and 12 months and 25 and 16 months for MD and LD, respectively. The median pretreatment PSA and Gleason score (GS) for LD were 10.2 ng/mL (0.2-450) and 7 (3-9). For MD, the presenting PSA (> 20 vs 20; 20.7 and 12.2 months vs PSA .05. Five patients with AI have died; the mean time to death from development of AI was 1.7 years. Conclusion Longer-duration follow-up of a single cohort supports IAS as a viable treatment option for men with advanced CaP. The PSA at the start of IAS is predictive of cycle length and time spent off therapy for patients with nonmetastatic disease.

Global update on defining and treating high‐risk localized prostate cancer with leuprorelin: a Japanese perspective – the effect of primary androgen deprivation therapy on stage C prostate cancer

Stage C prostate cancer, where the tumour has extended beyond the capsule of the prostate, is typically a high-risk disease. According to the National Cancer Institute Physician Data Query the treatments of choice for stage C disease comprise external beam radiation therapy (with or without the addition of adjuvant hormone therapy), androgen deprivation by either surgery or hormone therapy, radical prostatectomy, or careful observation. From 2001, the Japanese Urological Association initiated computer-based registration of all patients with prostate cancer in Japan. Data show that overall, 57% of all patients and 46% of those with T1c to T3 disease had primary androgen deprivation therapy (PADT). Similarly, the Japanese Prostate Cancer Group undertook a large-scale epidemiological surveillance study in Japan and found that the most commonly used hormone therapy is PADT, regardless of disease stage. To date, two randomized, controlled trials of the effect of PADT on stage C prostate cancer in elderly (> or =75 years old) patients have been undertaken in Japan. The results showed that patients with locally advanced prostate cancer treated with PADT are likely to have a life-expectancy similar to that of the normal population. In one study, combined androgen blockade (CAB) with leuprorelin plus chlormadinone appeared to prolong time to disease progression when compared with leuprorelin monotherapy, but there was no difference in survival between these treatment groups. In a second study CAB with an luteinizing hormone-releasing hormone (LHRH) agonist plus bicalutamide was found to prolong time to progression when compared with LHRH agonist monotherapy, but survival results for these regimens are still awaited.

Abarelix For Injectable Suspension: First-In-Class Gonadotropin-Releasing Hormone Antagonist For Prostate Cancer

Abarelix, a gonadotropin-releasing hormone antagonist, with its indication for advanced symptomatic prostate cancer, represents the newest category of hormonal therapy introduced in the past 15 years. Results from Phase II and III clinical trials demonstrate the advantages of abarelix over commonly used luteinizing hormone-releasing hormone (LHRH) agonist therapy: abarelix does not cause a surge in serum testosterone that can precipitate a flare phenomenon or worsening of disease, particularly dangerous for patients with metastatic, symptomatic disease, and produces medical castration more quickly. Abarelix was also demonstrated to promptly and substantially reduce follicle-stimulating hormone levels to lower than LHRH agonist. Study results demonstrate effective anticancer responses during extended exposure to abarelix: improvements in pain score and/or analgesic use, improvements in urinary symptoms (including urinary catheter removal) and complete avoidance of bilateral orchiectomy for patients undergoing at least 12 weeks of treatment. In Phase III clinical trials, abarelix demonstrated a similar overall safety profile when compared with LHRH agonist monotherapy, and a superior safety profile when compared with LHRH agonist plus antiandrogen combination therapy. Abarelix patients experienced a greater incidence of immediate-onset systemic allergic reactions as compared with control arms.

Efficacy of primary hormone therapy for localized or locally advanced prostate cancer: results of a 10‐year follow‐up

To evaluate the efficacy of primary hormone therapy for localized or locally advanced prostate cancer, by analysing the 10-year survival rates for men with localized or locally advanced prostate cancer treated with primary hormone therapy or prostatectomy. Between February 1993 and March 1995, men with T1b, T1c or T2-3 N0M0 prostate cancer were enrolled. In all, 176 men who had a prostatectomy were assigned to Study 1 and were given adjuvant luteinizing hormone-releasing hormone (LHRH) agonist; 151 men who did not have a prostatectomy were assigned to Study 2 and had LHRH agonist monotherapy or combined androgen blockade. They were followed until death, loss to follow-up, or until the end of the observation period (31 March 2004). We analysed all cases in each study as a single population, and compared Study 1 with Study 2. The mean patient ages were 67.2 years in Study 1 and 75.7 years in Study 2. During a median of 10.4 years of follow-up, 20 men in Study 1 and 17 in Study 2 died from prostate cancer, and 21 men in Study 1 and 50 in Study 2 died from other causes. In Study 1, the 10-year overall survival rate was 73% and the 10-year cause-specific survival rate was 86%, vs 41% and 78% in Study 2. Overall survival curves were similar to expected survival curves in both studies. There was no significant difference between studies in cause-specific survival. The progression of prostate cancer was retarded by primary hormone therapy in men with localized or locally advanced prostate cancer. With primary hormone therapy or prostatectomy, the men had a life-expectancy similar to that of the normal population.

Hormone Therapy for Prostate Cancer: Guidelines versus Clinical Practice

Objectives In 2005, the European Association of Urology (EAU) published an update of the EAU guidelines on prostate cancer. This report evaluates whether these guidelines reflect the current therapy standards in daily clinical practice. Methods An interactive meeting was held comparing the current therapy standards in prostate cancer with the EAU guidelines. This paper contains a summary of the outcomes of this meeting. Results The EAU guidelines recommend curative therapy for patients diagnosed with localized prostate cancer (T1b–T2c). However, for unfit patients with a life expectancy of 5–10 yr and poorly differentiated tumours, the combination of radiotherapy and hormones is recommended. The majority of the delegates (68%) would also recommend combination therapy in the latter. However, 17% would prescribe luteinizing hormone releasing hormone (LHRH) agonist monotherapy for this type of patient. Although radiotherapy in combination with adjuvant hormone therapy is recommended for patients with advanced prostate cancer (T3–T4), only 30% of the delegates agreed. Almost half of the urologists (48%) would prescribe LHRH agonist monotherapy. The patient's age appears to be a major differentiator for urologists to select the most appropriate treatment strategy. Approximately half of the urologists adhered to the guidelines for patients with a biochemical relapse after radical prostatectomy and would recommend radiotherapy. Around one third of the urologists would prescribe LHRH agonist monotherapy. The discussion on defining the moment for initiating LHRH agonist monotherapy remained inconclusive. Different practice patterns were noted for patients with positive nodes and patients with metastatic disease. Conclusions The EAU guidelines, although followed by a majority of physicians, do not give direction for all patients seen in daily clinical practice. Large variations in practice exist among the participating urologists.

Luteinizing Hormone-releasing Hormone Agonist Monotherapy for Prostate Cancer: Outcome and Prognostic Factors

We assessed the outcome and prognostic factors in men with prostate cancer after luteinizing hormone-releasing hormone agonist monotherapy. Between April 1998 and August 2002, 62 men with prostate cancer who were treated with monotherapy at our institution were included in this analysis. Prostate-specific antigen (PSA) failure-free (bNED) survival was calculated using Kaplan-Meier methods. Prognostic factors were evaluated using Cox proportional hazards regression model. We reviewed the data of patients, with a median follow-up from the commencement of monotherapy of 26 months. The overall survival rate at 3 years was 89.9%. The bNED survival rate was 63.7% at 3 years. Of the 20 patients with clinical stage B, 2 progressed to PSA failure, whereas PSA failure was seen in 8 of 30 patients with stage C and 8 of 12 patients with stage D. The significant factors for bNED status were an initial PSA level of <30 ng/ml (p=0.0044), achievement of PSA nadir level of <2.0 ng/ml (p<0.001), and Gleason score of <or=6 (p<0.001). Patients with high clinical stage, a high initial PSA level of >or=30 ng/ml, and high Gleason score of >or=7 are at increased risk for PSA failure. Failure to achieve PSA nadir level of <2.0 ng/ml is an important predictor of the progression. The use of PSA nadir can provide useful guidelines for the reconsideration of treatment in patients who have received monotherapy.

Evolution of therapeutic approaches with luteinizing hormone–releasing hormone agonists in 2003

The role of hormone therapy in the current era of widespread testing for prostate-specific antigen (PSA) continues to evolve. Although still used in patients with metastatic disease, the most common uses of luteinizing hormone–releasing hormone (LHRH) agonist therapy are in the adjuvant and neoadjuvant settings with radiotherapy and sometimes with radical prostatectomy, as well as in the treatment of PSA-only recurrence. Immediate (adjuvant) hormone therapy after prostatectomy may provide a survival advantage relative to deferred treatment in high-risk patients, whereas the survival benefit of adjuvant therapy with radiation is clearer. Combined androgen blockade with an LHRH agonist and a nonsteroidal antiandrogen provides a very modest but statistically significant survival benefit relative to LHRH agonist monotherapy in patients with metastatic disease, but it has not been proved in those with less advanced disease. Intermittent hormone therapy appears to be effective in maintaining disease control for several years, but randomized studies are needed to determine if survival is at least equivalent to continuous therapy. Finally, LHRH agonist therapy is commonly used in the setting of biochemical or PSA-only recurrence. However, there are no randomized controlled trials to prove a survival benefit over observation. In summary, hormone therapy now plays a more important role at earlier stages of disease, consistent with the changing epidemiology of prostate cancer. Additional studies are needed, however, to define how to optimally use hormone therapy across various patient types.