Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide.

UNLABELLED: Study Type--Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Androgen deprivation therapy (ADT) is commonly used as a primary treatment for patients with prostate cancer (PCa) who are not eligible for radical treatment options. ADT is also used in patients with PCa as neo-adjuvant hormone therapy to reduce prostate volume and down-stage the disease before radiotherapy with curative intent. The present study showed that ADT with the gonadotropin hormone-releasing hormone (GhRH) antagonist degarelix is non-inferior to combined treatment with the LHRH agonist goserelin and bicalutamide in terms of reducing prostate volume during the treatment period of 3 months. Degarelix treatment evokes, however, significantly better relief of lower urinary tract symptoms in patients having moderate and severe voiding problems. OBJECTIVE: • To assess the efficacy of monthly degarelix treatment for reduction of total prostate volume (TPV), relief of lower urinary tract symptoms (LUTS) and improvement of quality of life (QoL) in patients with prostate cancer (PCa) using monthly goserelin as active control. METHODS: • This was a randomized, parallel-arm, active-controlled, open-label, multicentre trial on 182 patients treated with either monthly degarelix (240/80 mg) or goserelin (3.6 mg) for 12 weeks. • For flare protection, goserelin-treated patients also received daily bicalutamide (50 mg) during the initial 28 days. • Key trial variables monitored monthly were TPV (primary endpoint), serum testosterone, prostate-specific antigen (PSA), the International Prostate Symptom Score (IPSS) and the Benign Prostate Hyperplasia Impact Index. RESULTS: • In all, 175 patients completed the trial (96.1%). • At week 12, changes in TPV for degarelix and goserelin were similar (-37.2% vs -39.0%) and met the predefined non-inferiority criterion. • Decreases in IPSS were greater in degarelix than in goserelin-treated patients, differences being statistically significant in patients with baseline IPSS > 13 (-6.7 ± 1.8 vs -4.0 ± 1.0; P = 0.02). • The number of patients with an IPSS change of ≥ 3 over baseline was also significantly higher in patients treated with degarelix (61.0 vs 44.3%, P = 0.02). • Both treatments were safe and well tolerated. CONCLUSIONS: • Medical castration reduces TPV and could also improve LUTS in patients with PCa. • While the short-term efficacy of degarelix and goserelin + bicalutamide was the same in terms of TPV reduction, degarelix showed superiority in LUTS relief in symptomatic patients, which could highlight the different actions of these drugs on extrapituitary gonadotrophin-releasing hormone (GnRH) receptors in the bladder and/or the prostate.

Effect of endocrine treatment on voiding and prostate size in men with prostate cancer: a long-term prospective study.

OBJECTIVE: The aim of this study was to assess and quantify changes in voiding parameters and prostate size in men with prostate cancer from before the start of endocrine treatment and during long-term follow-up. MATERIAL AND METHODS: Seventy-seven patients were recruited from three clinics and followed prospectively until death, clinical deterioration making the patient unfit for participation, or the end of the study. Median age was 74 (range 54-85) years, and the median follow-up was 18 (3-90) months. Parameters and endpoints were total score on the Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire, maximum flow rate, postvoid residual volume, frequency and voided volume, and prostate volume on transrectal ultrasonography. RESULTS: All parameters improved significantly in the range of median 13-50% within the first 12 months. The greater part of the effect occurred during the first month, and thereafter the improvement rate slowed down. Intervention for local progression was estimated on Kaplan-Meier analysis to be about 20% after 4 years. 73% had a defined prostate-specific antigen nadir after a median of 6 (1-60) months with scheduled assessments up to 72 months after the nadir. All parameters were improved before the nadir and the improvement remained during biochemical progression except for the very latest visits where few patients contributed to the analyses. CONCLUSIONS: Androgen deprivation therapy improved lower urinary tract symptoms, objective voiding parameters and prostate volume in patients with prostate cancer who were not candidates for curative treatment. The improvement was significant within the first month and clinically relevant. Despite biochemical progression the effect may last for years, and only a minority will need intervention for local progression.

Is well-being associated with lower urinary tract symptoms in patients with stroke?

OBJECTIVE: This study aimed to assess self-reported well-being in a clinical sample of stroke patients and to identify possible associations with prevalence, severity and bother of lower urinary tract symptoms (LUTS). MATERIAL AND METHODS: A cross-sectional, clinical survey was initiated whereby stroke patients were invited to complete The WHO-Five Well-Being Index (WHO-5) and a LUTS instrument, the Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire. Of 519 stroke patients invited, 482 subjects were eligible and 407 (84%) respondents answered the questionnaires. RESULTS: Poor well-being (sum score <13) was reported by 22% of all stroke patients, for women 29% and for men 14%. Depression (sum score <8) was reported by 10%, for women 11% and for men 8%. Poor well-being was significantly (p < 0.01) associated with severity and bother of LUTS. Likewise, poor well-being was significantly (p < 0.001) associated with the prevalence of four different symptom groups of LUTS. CONCLUSIONS: The results indicate that poor well-being is present in stroke patients with LUTS, especially in women. Likewise, the data showed significant association between poor well-being and LUTS. Screening for well-being and LUTS in stroke patients is strongly recommended.

Significance of pretreatment cardiovascular morbidity as a risk factor during treatment with parenteral oestrogen or combined androgen deprivation of 915 patients with metastasized prostate cancer: evaluation of cardiovascular events in a randomized trial.

OBJECTIVE: This study aimed to evaluate prognostic risk factors for cardiovascular events during treatment of metastatic prostate cancer patients with high-dose parenteral polyoestradiol phosphate (PEP, Estradurin®) or combined androgen deprivation (CAD) with special emphasis on pretreatment cardiovascular disease. MATERIAL AND METHODS: Nine-hundred and fifteen patients with T0-4, Nx, M1, G1-3, hormone- naïve prostate cancer were randomized to treatment with PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or to flutamide (Eulexin®) 250 mg per os three times daily in combination with either triptorelin (Decapeptyl®) 3.75 mg i.m. per month or on an optional basis with bilateral orchidectomy. Pretreatment cardiovascular morbidity was recorded and cardiovascular events during treatment were assessed by an experienced cardiologist. A multivariate analysis was done using logistic regression. RESULTS: There was a significant increase in cardiovascular events during treatment with PEP in patients with previous ischaemic heart disease (p = 0.008), ischaemic cerebral disease (p = 0.002), intermittent claudication (p = 0.031) and especially when the whole group of patients with pretreatment cardiovascular diseases was analysed together (p < 0.001). In this group 33% of the patients had a cardiovascular event during PEP treatment. In the multivariate analysis PEP stood out as the most important risk factor for cardiac complications (p = 0.029). Even in the CAD group there was a significant increase in cardiovascular events in the group with all previous cardiovascular diseases taken together (p = 0.036). CONCLUSIONS: Patients with previous cardiovascular disease are at considerable risk of cardiovascular events during treatment with high-dose PEP and even during CAD therapy. Patients without pretreatment cardiovascular morbidity have a moderate cardiovascular risk during PEP treatment and could be considered for this treatment if the advantages of this therapy, e.g. avoidance of osteopenia and hot flushes and the low price, are given priority.

Are activity limitations associated with lower urinary tract symptoms in stroke patients? A cross-sectional, clinical survey.

OBJECTIVE: To assess self-reported activity limitations in a clinical sample of stroke patients and to identify their association with prevalence, severity and impact on daily life of lower urinary tract symptoms (LUTS). MATERIAL AND METHODS: A cross-sectional, clinical survey was initiated whereby stroke patients were invited to complete four activity limitations measurements: Barthel Index, mobility velocity, mobility distance, mobility aids and one LUTS measurement: the Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire. Of 519 stroke patients, 482 subjects were eligible. RESULTS: The response rate was 84%. The activity limitations were reported by 17-34% depending on the measurement. Mobility velocity was highly significantly associated (p=0.01) with severity of LUTS. In the LUTS incontinence symptom group, Barthel Index and mobility velocity were significantly associated with prevalence [p=0.03, odds ratio (OR) 2.08 and p=0.05, OR 1.87, respectively]. Barthel Index and mobility distance were also associated with severity (p=0.03 and p=0.04, respectively) and Barthel Index was associated with the prevalence of bother (p=0.02, OR 2.12). CONCLUSION: This study indicate for the first time that activity limitations are closely related to LUTS in stroke patients and that rehabilitation should also be directed towards the treatment of LUTS.

Prevalence of lower urinary tract symptoms (LUTS) in stroke patients: a cross-sectional, clinical survey.

AIMS: The aims of this study were primarily to investigate the prevalence, severity and impact on daily life of Lower Urinary Tract Symptoms (LUTS) in a clinical sample of stroke patients and secondly to identify factors associated with LUTS. MATERIALS AND METHODS: This was a cross-sectional, hospital based survey whereby stroke patients were invited by letter to complete The Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire at least 1 month following their stroke. Subjects were asked to report the frequency and severity of their symptoms (symptom score) and the impact of each symptom on their daily life (bother score) over the previous fortnight. Of 519 stroke patients invited, 482 subjects were eligible. RESULTS: The response rate was 84%. The period prevalence of at least one symptom was 94%; the most frequent symptom was nocturia (76%) followed by urgency (70%) and daytime frequency (59%). The most severe symptom was urgency followed by nocturia and daytime frequency. Among respondents who had at least one symptom, the prevalence of bother was 78%. Likewise the most frequent bothersome symptom was nocturia (53%), followed by urgency (48%) and daytime frequency (40%). Paresis in legs, symptoms of urinary incontinence on admission, and use of analgesics were significantly associated with severity, whereas the prevalence and bother of LUTS could not be associated with other patient characteristics. CONCLUSION: LUTS are highly prevalent in stroke patients and have a major impact on daily life.

Eosinophilic cystitis induced by penicillin.

A 30-year-old woman developed classic symptoms of painful bladder disease and eosinophilic cystitis as an adverse effect of penicillin for abdominal actinomycosis. The symptoms were reversible after stopping penicillin.

Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5.

OBJECTIVE: To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP; Estradurin) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular events. MATERIAL AND METHODS: In total, 910 eligible patients with T0-4, NX, M1, G1-3 prostate cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or flutamide (Eulexin) 250 mg t.i.d. per os in combination with either triptorelin (Decapeptyl) 3.75 mg i.m. per month or on an optional basis bilateral orchidectomy. RESULTS: At this final evaluation of the trial 855 of the 910 patients were dead. There was no difference between the treatment groups in terms of biochemical or clinical progression-free survival or in overall or disease-specific survival. There was no difference in cardiovascular mortality, but a significant increase in non-fatal cardiovascular events in the PEP arm (p<0.05) predominantly caused by an increase in ischemic heart and heart decompensation events. There were 18 grave skeletal events in the CAD group but none in the PEP group (p=0.001). CONCLUSIONS: PEP has an anticancer efficacy equal to CAD and does not increase cardiovascular mortality in metastasized patients, but carries a significant risk of non-fatal cardiovascular events, which should be balanced against the skeletal complications in the CAD group. It is feasible to use Estradurin in the primary or secondary endocrine treatment of metastasized patients without prominent cardiac risk factors and especially those with osteoporosis.

Pelvic floor muscle training before transurethral resection of the prostate: a randomized, controlled, blinded study.

UNLABELLED: OBJECTIVE To evaluate the effect of preoperative pelvic floor muscle training (PFMT) in men scheduled for transurethral resection of the prostate (TURP) in a randomized, single-blind study. MATERIAL AND METHODS: Fifty-eight men with benign prostatic obstruction were included, and 49 completed the study (training group, n=26; control group, n=23). The preoperative training included a 1-h individual lesson, three 1-h group lessons and a home training programme. Postoperatively and before discharge from hospital both groups received verbal instructions regarding PFMT. Pelvic floor muscle function was assessed by anal examination before and 4 weeks after surgery by one physiotherapist who was blinded to the randomization. The primary outcome parameter was the total score on the Danish Prostatic Symptom Score questionnaire. Secondary outcome measures were other subjective and objective voiding and incontinence parameters and four tests of the pelvic floor muscle: function; strength; static endurance; and dynamic endurance. RESULTS: Baseline characteristics were similar in the two groups. Improved static endurance occurred in the training group but not in the control group (p=0.004). Regarding dynamic endurance, a difference in favour of training developed between the groups (p=0.049). Many men produced results that were outside the test scales. At follow-up at 2 and 4 weeks and 3 months there were no differences between the groups in any of the lower urinary tract parameters. CONCLUSIONS: Preoperative PFMT produced a significant improvement in pelvic floor muscle endurance after TURP, but clinically relevant storage or voiding improvements did not occur. Pelvic floor muscle assessment tests need to be sex-specific.

The Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire is reliable in stroke patients.

AIMS: To investigate the test-retest reliability of Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire in a sample of stroke patients. METHODS: A prospective study design was used in which the stroke patients were invited to complete a postal self-administrated DAN-PSS-1 questionnaire twice. The questionnaire consists of 12 questions related to lower urinary tract symptoms (LUTS). The participants were asked to state the frequency and severity of their symptoms (symptom score) and its impact on their daily life (bother score). Seventy-one stroke patients were included and 59 (83%) answered the questionnaire twice. The reliability test was done in two aspects: (a) detecting the frequency of each symptom and its bother factor, the scores were reduced to a two-category scale (=0, >0) and simple kappa statistics was used; (b) detecting the severity of each symptom and its bother factor, the total scale (0-3) and weighted kappa statistics was used. RESULTS: The proportion of agreement for the frequency symptom scores ranged from 76% to 97% and the simple kappa coefficient ranged from poor (kappa = 0.00) to excellent (kappa = 0.91). The proportion of agreement for the corresponding bother scores ranged from 76% to 95% and the simple kappa coefficient ranged from good (kappa = 0.61) to excellent (kappa = 0.84). The weighted kappa coefficient for the severity symptom scores ranged from moderate (kappa(w) = 0.43) to good (kappa(w) = 0.75) and the corresponding bother scores ranged from moderate (kappa(w) = 0.48) to good (kappa(w) = 0.68). CONCLUSIONS: The DAN-PSS-1 questionnaire had acceptable test-retest reliability and may be suitable for measuring the frequency and severity of LUTS and its bother factor in stroke patients.

Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years.

OBJECTIVE: The Early Prostate Cancer (EPC) programme is evaluating the efficacy and tolerability of bicalutamide following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N + ) non-metastatic prostate cancer. Herein we report the latest findings after a median follow-up period of 7.1 years from the Scandinavian Prostate Cancer Group (SPCG)-6 study, one of three trials in the EPC programme. MATERIAL AND METHODS: A total of 1218 patients were randomized on a 1:1 basis to either bicalutamide 150 mg/day (n=607) or placebo (n=611) following standard care; 81.4% were followed conservatively (watchful waiting). The primary endpoints were objective progression-free survival (PFS) and overall survival (OS). RESULTS: In patients with localized disease there was no significant difference in PFS [hazard ratio (HR) 0.85; 95% CI 0.69-1.06; p=0.15] and a trend towards decreased OS with bicalutamide plus standard care compared with standard care alone (HR 1.23; 95% CI 0.96-1.58; p=0.11). In patients with locally advanced disease, bicalutamide significantly improved PFS, reducing the risk of progression by 53% compared with standard care alone (HR 0.47; 95% CI 0.37-0.59; p<0.001). The median time to progression was 8.8 years for bicalutamide plus standard care and 7.1 years for standard care alone. There was a significant improvement in OS with bicalutamide plus standard care, with a reduction in the risk of death of 35% versus standard care alone (HR 0.65; 95% CI 0.50-0.85; p=0.001). CONCLUSION: This analysis of the SPCG-6 study showed that bicalutamide plus standard care offers significant PFS and OS benefits for patients with locally advanced disease, but not for those with localized disease.

Experience with Memokath 051 ureteral stent.

OBJECTIVE: The Memokath 051 is a thermo-expandable titanium-nickel spiral developed for long-term ureteral stenting. The aim of this study was to investigate the drainage and safety aspects of this stent. MATERIAL AND METHODS: A total of 3-4 consecutive patients were included: 22 had benign strictures, five had post-irradiation strictures and seven had malignant strictures. Follow-up visits took place after 1 month and thereafter every 3 months for at least 1 year. RESULTS: Thirty-three patients had a total of 37 stents inserted uni- or bilaterally. Pre-insertion dilatation was impossible in one patient and difficult in two, all of whom had post-irradiation strictures. Insertion was complicated in seven patients and uneventful in the other 26. Fifteen stents were in place and functioning with no discomfort or complications at death or the end of follow-up (median 14 months; range 3-30 months), while 22 were non-functioning after 1 day to 16 months (median 5 months). Of these 22 stents, 10 had migrated and 12 were malfunctioning. Among the latter, stricture length was underestimated in four patients, and the stents were replaced successfully shortly after insertion. Four stents were occluded by stones after 1-10 months. No tissue ingrowth was seen. Stent removal was easy, with the exception of one patient with stent calcification. CONCLUSIONS: The Memokath 051 is an alternative for selected patients with non-curable ureteral obstruction but is not suitable for use in patients with functional stenosis or stone formation. Insertion and removal are easy in most patients, but can be difficult or impossible, especially in patients with post-irradiation strictures and retroperitoneal fibrosis. Migration and obstruction can occur and careful follow-up is necessary.

Bicalutamide (150 mg) versus placebo as immediate therapy alone or as adjuvant to therapy with curative intent for early nonmetastatic prostate cancer: 5.3-year median followup from the Scandinavian Prostate Cancer Group Study Number 6.

PURPOSE: We evaluated the benefits of adding 150 mg bicalutamide to standard care, that is radical prostatectomy, radiotherapy or watchful waiting (WW), in patients with localized or locally advanced prostate cancer. MATERIALS AND METHODS: A total of 1,218 men with T1-4, M0, any N prostate cancer were recruited from 62 Scandinavian centers and randomized 1:1 to 150 mg bicalutamide or placebo plus standard care. Primary end points were progression-free survival (PFS) and overall survival. RESULTS: At a median 5.3-year followup patients with locally advanced disease had improved survival with bicalutamide (HR 0.68, 95% CI 0.50 to 0.92), while those with localized disease had decreased survival with bicalutamide (HR 1.47, 95% CI 1.06 to 2.03). Bicalutamide significantly improved PFS, decreasing the risk of disease progression by 43% compared with placebo (HR 0.57, 95% CI 0.48 to 0.68, p<0.0001). The rate of events was 35.4% for bicalutamide and 46.2% for placebo. Patients with locally advanced disease gained the greatest PFS benefits with bicalutamide (HR 0.40, 95% CI 0.31 to 0.52). Since 81% of the trial population were untreated before entry and would otherwise have undergone WW, the findings essentially reflect the results of immediate hormone therapy vs WW. CONCLUSIONS: Bicalutamide (150 mg) provides significant benefit in patients with locally advanced disease. In previously untreated patients there may be a tumor burden below which endocrine therapy provides no benefit or may even decrease survival.