Comparison of intermittent and continuous androgen deprivation and quality of life between patients with locally advanced and patients with metastatic prostate cancer: a post hoc analysis of the randomized FinnProstate Study VII.

OBJECTIVE: The aim of the study was to compare intermittent (IAD) and continuous (CAD) androgen deprivation therapy (ADT) between locally advanced (M0) and metastatic (M1) prostate cancer, and the effect of ADT on the quality of life. MATERIAL AND METHODS: In total, 852 men with advanced prostate cancer were enrolled to receive goserelin acetate for 24 weeks. Of these, 554 patients whose prostate-specific antigen (PSA) decreased to less than 10 ng/ml or by at least 50% (<20 ng/ml at baseline) were randomized to IAD or CAD. In the IAD arm, ADT was resumed for at least 24 weeks whenever PSA increased to greater than 20 ng/ml or above baseline. RESULTS: Median follow-up time was 65 months. Median times from randomization to progression, death, prostate cancer death and treatment failure in M0 and M1 patients were 46.8 and 21.4, 57.6 and 40.3, 59.5 and 40.7, and 41.9 and 20.0 months, respectively (p < 0.001). No significant differences emerged between IAD and CAD. ADT showed a beneficial effect on pain, activity limitation and social functioning in M1 patients, and a deleterious effect on physical capacity in M0 patients and on sexual functioning in both groups. IAD offered extra benefit for activity limitation, social functioning and recovery of sexual functioning. CONCLUSIONS: IAD is as efficient as CAD in treatment of locally advanced and metastatic prostate cancer. ADT improves quality of life in M1 patients, with IAD offering extra benefit.

Advanced prostate cancer treated with intermittent or continuous androgen deprivation in the randomised FinnProstate Study VII: quality of life and adverse effects.

BACKGROUND: Intermittent dosing may reduce the adverse events (AEs) of androgen-deprivation therapy (ADT). OBJECTIVE: To compare intermittent androgen deprivation (IAD) and continuous androgen deprivation (CAD) with regard to health-related quality of life (QoL). DESIGN, SETTING, AND PARTICIPANTS: A total of 852 men with advanced prostate cancer (PCa) were enrolled to receive goserelin acetate 3.6 mg every 28 d for 24 wk. A total of 554 patients whose prostate-specific antigen (PSA) decreased to <10 ng/ml or by ≥50% (<20 ng/ml at baseline) were randomised to IAD or CAD. INTERVENTION: In the IAD arm, ADT was resumed for at least 24 wk whenever PSA increased >20 ng/ml or above baseline. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: QoL was monitored with a validated Cleary 30-item questionnaire and analysed by the Mann-Whitney U test, 0.5 standard deviation rule, and repeated measures analysis of variance. AEs and adverse drug reactions (ADRs) were analysed by the chi-square test. RESULTS AND LIMITATIONS: Median follow-up was 65 mo. Significant differences in QoL emerged in activity limitation, physical capacity, and sexual functioning, favouring IAD. No significant differences emerged in the prevalence of AEs: 87 patients in the IAD arm (31.8%) and 95 in the CAD arm (33.9%) had cardiovascular (CV) AEs (p=0.59), with 25 (9.1%) and 29 (10.4%) withdrawn (p=0.62), and 21 (7.7%) and 24 (8.6%) dying because of a CV event (p=0.70), respectively; bone fractures occurred in 19 (6.9%) and 15 (5.4%) patients (p=0.44), respectively. Hot flushes or night sweats were the most common ADRs (47.1% vs 50.4%; p=0.44). Erectile dysfunction (15.7% vs 7.9%; p=0.042) and depressed mood (2.2 vs 0%; p=0.032) were more common in the IAD arm. CONCLUSIONS: IAD showed benefits in the treatment of advanced PCa with respect to QoL. The prevalence of AEs was not significantly lower with IAD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00293670.

The FinnProstate Study VII: intermittent versus continuous androgen deprivation in patients with advanced prostate cancer.

PURPOSE: We conducted a randomized trial to compare intermittent and continuous androgen deprivation in patients with advanced prostate cancer. We studied time to progression, overall and prostate cancer specific survival, and time to treatment failure. MATERIALS AND METHODS: Between May 1997 and February 2003, 852 men with locally advanced or metastatic prostate cancer were enrolled to receive androgen deprivation therapy for 24 weeks. Patients in whom prostate specific antigen decreased to less than 10 ng/ml, or by 50% or more if less than 20 ng/ml at baseline, were randomized to intermittent or continuous androgen deprivation. In the intermittent therapy arm androgen deprivation therapy was withdrawn and resumed again for at least 24 weeks based mainly on prostate specific antigen decrease and increase. RESULTS: There were 298 patients who did not meet the randomization criteria. The remaining 554 patients were randomized, with 274 (49.5%) to intermittent androgen deprivation and 280 (50.5%) to the continuous androgen deprivation arm. Median followup was 65.0 months. Of these patients 392 (71%) died, including 186 (68%) in the intermittent androgen deprivation arm and 206 (74%) in the continuous androgen deprivation arm (p=0.12). There were 248 prostate cancer deaths, comprised of 117 (43%) in the intermittent androgen deprivation and 131 (47%) in the continuous androgen deprivation arm (p=0.29). Median times from randomization to progression were 34.5 and 30.2 months in the intermittent androgen deprivation and continuous androgen deprivation arms, respectively. Median times to death (all cause) were 45.2 and 45.7 months, to prostate cancer death 45.2 and 44.3 months, and to treatment failure 29.9 and 30.5 months, respectively. CONCLUSIONS: Intermittent androgen deprivation is a feasible, efficient and safe method to treat advanced prostate cancer compared with continuous androgen deprivation.

Finnish multicenter study comparing intermittent to continuous androgen deprivation for advanced prostate cancer: interim analysis of prognostic markers affecting initial response to androgen deprivation.

PURPOSE: Intermittent androgen deprivation has been proposed to prolong hormone sensitivity and improve quality of life in patients with advanced prostate cancer. The FinnProstate Study VII has been performed to identify patients who might benefit from intermittent androgen deprivation. In this interim analysis we evaluated which prognostic markers affect the initial response to androgen deprivation therapy. MATERIALS AND METHODS: A total of 856 men with locally advanced or metastatic prostate cancer were enrolled and given androgen deprivation therapy for 24 weeks to ensure hormone sensitivity. Patients with hormone sensitive prostate cancer were randomized 1:1 to continuous androgen deprivation or intermittent androgen deprivation. The randomization criteria were prostate specific antigen decrease to less than 10 ng/ml or by more than 50% if less than 20 ng/ml at baseline. RESULTS: There were 292 patients (34%) who did not meet the randomization criteria (group 1). The remaining 564 patients (66%) were randomized to intermittent androgen deprivation or continuous androgen deprivation (group 2). Mean prostate specific antigen (834 vs 151 ng/ml), mean alkaline phosphatase (793 vs 292 IU/l), proportion of T4 tumors (37% vs 24%), poorly differentiated cancers (39% vs 26%), metastatic disease (82% vs 51%) and number of skeletal hot spots in M1 disease (more than 5 hot spots 72% vs 42%) were significantly higher in group 1 than in group 2. CONCLUSIONS: Patients with the most advanced prostate cancer and poorest prognosis do not show adequate biochemical prostate specific antigen response to androgen deprivation therapy but should be assessed for eligibility to receive nonendocrine treatment.

The expression and prognostic value of alpha-, beta- and gamma-catenins in renal cell carcinoma.

BACKGROUND: Catenins have prognostic value in several human tumours. The aim of the study was to analyse the prognostic value of catenin expression in a prospectively followed series of renal cell carcinoma. PATIENTS AND METHODS: One hundred and twenty-four renal cell carcinomas were prospectively followed-up for a mean of 3.5 years and the survival data of patients were related to standard prognostic factors and to the results of alpha-, beta- and gamma-catenin immunohistochemistry. The data of catenin immunohistochemistry were also related to the clinical and histopathological characteristics of the tumours. RESULTS: Low cytoplasmic alpha-catenin expression was related to lymphatic tumour growth (p=0.02) and to tumour necrosis (p=0.02). The weak expression intensity of beta-catenin on cell membranes was related to venous growth inside the tumour (p=0.02), extratumoural venous growth (p=0.03) and to perineural growth (p<0.001). Nuclear gamma-catenin expression was strongly associated with clear cell type (p=0.0001) and high WHO grade (p=0.038). Short recurrence-free survival was predicted by weak membranous alpha-catenin (p=0.015) and beta-catenin (p=0.006) expression intensity, while their cytoplasmic expression was of lower significance (p=0.07 and 0.045, respectively). All the conventional prognostic factors predicted short recurrence-free survival: Fuhrman classification (p=0.02), WHO grade (p=0.026), perineural growth (p=0.013), venous invasion (p=0.0024), tumour size (p=0.004) and T-category (p=0.0001). Independent predictors of short recurrence-free survival were weak membranous expression intensity of beta-catenin (RR=0.15, p=0.004), high T-category (RR=2.70, p=0.0001) and high WHO grade (RR=2.24, p=0.025). CONCLUSION: The results show that immunohistochemical analysis of beta-catenin expression may be used as an indicator of aggressiveness in renal cell carcinoma.