Background: Androgen deprivation therapy (ADT) is a non-curative but essential treatment of prostate cancer with severe side effects. Therefore, both over- and underuse should be avoided. We investigated adherence to guidelines for ADT following radical prostatectomy through Swedish population-based data.Material and methods: We used the database Uppsala/Örebro PSA cohort (UPSAC) to study men with localised or locally advanced prostate cancer at diagnosis (clinical stage T1-T3, N0-NX, M0-MX, and prostate-specific antigen (PSA)
Old age at prostate cancer diagnosis has been associated with poor prognosis in several studies. We aimed to investigate the association between age at diagnosis and prognosis, and if it is independent of tumor characteristics, primary treatment, year of diagnosis, mode of detection and comorbidity.
We conducted a nation-wide cohort study including 121?392 Swedish men aged 55-95 years in Prostate Cancer data Base Sweden 3.0 diagnosed with prostate cancer in 1998-2012 and followed for prostate cancer death through 2014. Data were available on age, stage, grade, prostate-specific antigen (PSA)-level, mode of detection, comorbidity, educational level and primary treatment. We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).
With increasing age at diagnosis, men had more comorbidity, fewer PSA-detected cancers, more advanced cancers and were less often treated with curative intent. Among men with high-risk or regionally metastatic disease, the proportion of men with unknown M stage was higher among old men versus young men. During a follow-up of 751?000 person-years, 23?649 men died of prostate cancer. In multivariable Cox-regression analyses stratified by treatment, old age at diagnosis was associated with poorer prognosis among men treated with deferred treatment (HRage 85+ versus 60-64: 7.19; 95% CI: 5.61-9.20), androgen deprivation therapy (HRage 85+ versus 60-64: 1.72; 95% CI: 1.61-1.84) or radical prostatectomy (HRage 75+ versus 60-64: 2.20; 95% CI: 1.01-4.77), but not radiotherapy (HRage 75+ versus 60-64: 1.08; 95% CI: 0.76-1.53).
Our findings argue against a strong inherent effect of age on risk of prostate cancer death, but indicate that in current clinical practice, old men with prostate cancer receive insufficient diagnostic workup and subsequent curative treatment.
Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), Laval University, 2705 Laurier Boulevard, Quebec City, Quebec, Canada G1V 4G2. firstname.lastname@example.org
The last 20 years have witnessed major advances in the field of prostate cancer, both in terms of diagnosis and treatment. Using screening with PSA, 99% of prostate cancers can now be diagnosed at a clinically localized or potentially curable stage. Over a 11-year period starting in 1988, the Québec screening study performed among 45,000 men aged 45-80 years has shown that the prostate cancer death incidence has decreased by 64% in men who had screening. The impact of screening, however, requires early application of the most efficacious treatments. In this context, the most important recent therapeutic advance in the field of prostate cancer is androgen blockade, namely medical castration with LHRH agonists, the availability of pure antiandrogens and combined androgen blockade (CAB) using medical or surgical castration in association with a pure antiandrogen. In the six studies performed in localized or locally advanced disease, the improved cancer-specific survival ranges between 37 and 81% at 5 years of follow-up for patients who received androgen blockade. On the other hand, data already available show that long term and continuous (not intermittent) androgen blockade is highly efficient and can achieve long term control or possible cure of localized prostate cancer.
To describe patterns of initiation of androgen deprivation therapy (ADT) in a population-based cohort of patients with prostate cancer.
All patients with prostate cancer in Ontario, Canada, who started =90 days of ADT at age =66 years in 1995-2005 were classified by ADT regimen: medical castration [oestrogen and/or luteinizing hormone-releasing hormone (LHRH) agonist); orchidectomy; antiandrogen monotherapy; combined androgen blockade (CAB) medical (medical castration plus antiandrogen); CAB surgical (orchidectomy plus antiandrogen). Indications for ADT were as follows: neoadjuvant (short-term before prostatectomy or radiation therapy); adjuvant (long-term with prostatectomy or radiation therapy); metastatic disease; biochemical recurrence; primary (localized disease); other. We examined trends in ADT regimen and indication over time.
The number of patients initiating ADT increased from 1995 to 2001 (2106-2916 per year) and declined thereafter to 2200-2300 annually (total n= 26,809). However, prostate cancer prevalence doubled over these years, and the rate of ADT initiation decreased from 16 to 7 per 100 person-years. Patterns varied by regimen and indication. Medical castration increased from 12% of all ADT in 1995 to 47% in 2005; orchidectomy decreased from 17 to 4%. Use for metastatic disease remained stable, but adjuvant therapy increased from
Adherence has not been studied in male oncology populations. The aim of this study on both the prescriber and user perspectives in prostate cancer treatment was to analyse real-life prescribing patterns of anti-androgens (AA), primarily bicalutamide, and factors influencing the patients' adherence to treatment.
A nationwide clinical cohort of incident prostate cancer, PCBaSe, was linked to the Swedish Prescribed Drug Register. Men with a planned first line monotherapy AA treatment were identified; dosages and extent of off-label treatment were investigated. Cumulative incidence proportions for reasons for drug discontinuation were calculated. Factors potentially influencing adherence were explored using the medical possession ratio based on the individual prescribed daily dose.
First line monotherapy AA was planned in 4.4Â % of all incident cases and in 2.1Â % of low risk disease cases. Among 1,406 men prescribed bicalutamide, 1,109 (79Â %) received the approved daily dose of 150Â mg. Discontinuation reasons differed with disease severity. Off-label, low-dose prescription associated with age above 75Â years and disease categorised as low risk was noted in 297 men (21Â %). Sixty percent of the men adhered well, i.e. to =80Â %. Age above 75Â years and less severe disease were both negatively associated with adherence.
Patient age and tumour risk group influenced the prescriber's choice of dose, pointing to important issues for critical reflection. Possible over-treatment was noted in low risk disease. Interventions to increase adherence in older men and in men with less severe disease are worth considering after critically reviewing the appropriateness of the treatment indication, especially in the latter case.
• To describe clinical and histopathological characteristics of Finnish familial prostate cancer (PCa) through a detailed analysis of cases in families.
• In total, 202 Finnish families with 617 histopathologically confirmed PCa cases of confirmed genealogy were collected. • Complete clinical data, including age and prostate-specific antigen (PSA) at diagnosis, stage, grade and primary treatment, were gathered. The mean (range) number of affected men per family was 3 (2-8). • All the available diagnostic biopsy samples (n= 323) were collected and regraded by the same uropathologist. • A population-based cohort of 3011 hospital district Pirkanmaa PCa patients was used as a control group.
• The mean (range) year of diagnosis of PCa was 1993 (1962-2006) and the mean (range) age at diagnosis was 68 (43-98 years). • The median (range) primary PSA level was 12.0 (0.8-11 000) ng/mL. After regrading, the Gleason score was =6 in 38%, 7 in 37% and =8 in 25% of men. • The subset of familial PCa men diagnosed after 1995 had higher PSA levels (P= 9.9 × 10(-6) ) and an earlier age of onset (P= 1.7 × 10(-6) ) than men in the control group, although there were no differences in cancer-specific survival.
• We observed an earlier age of onset and higher PSA in familial PCa. • However, differences between sporadic and familial or hereditary PCa cannot be truly solved until genetic testing of high-risk genes in addition to family history is used to define PCa families. • We also emphasize that, when histological samples are collected over a longer study period, reanalysis of the samples by the same experienced uropathologist should be considered.
The optimum treatment of prostate cancer recurrence following radiation therapy (RT) remains controversial due to the lack of long-term data.
Our aim was to review the survival of patients who underwent salvage cryotherapy to the prostate gland for biopsy-proven recurrent prostate cancer and establish prognostic indicators.
A retrospective analysis was performed on all patients undergoing salvage cryotherapy at an academic urology unit for biopsy-proven locally recurrent prostate cancer after RT from 1995 to 2004. Patients' preoperative, perioperative, and postoperative data were reviewed and recorded.
Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon.
The primary outcome was survival. Secondary outcomes were disease-free survival (DFS), metastasis-free survival, and progression to androgen-deprivation therapy.
Of 187 patients, 176 had records available for follow-up (follow-up rate: 94%). Mean follow-up was 7.46 yr (range: 1-14 yr). Fifty-two patients were followed for >10 yr. DFS at 10 yr was 39%. Risk factors for recurrence were presalvage prostate-specific antigen (PSA), preradiation, and presalvage Gleason score. A PSA nadir >1.0 ng/dl was highly predictive of early recurrence.
Salvage cryotherapy led to an acceptable 10-yr DFS. Presalvage PSA and Gleason score were the best predictors of disease recurrence. A PSA nadir >1 ng/dl following cryotherapy indicated a poor prognosis, and recurrence of disease was universal in these patients.
Metformin, a biguanide antihyperglycemic drug, has been shown to improve ovarian function and glucose metabolism in women with polycystic ovary syndrome (PCOS), but results concerning its effects on insulin sensitivity are controversial. Oral contraceptive pills are commonly used in the treatment of PCOS; but, like metformin, their influence on insulin sensitivity is not well known. We randomized 32 obese (body mass index > 27 kg/m2) women with PCOS, either to metformin (500 mg x 2 daily for 3 months, then 1,000 mg x 2 daily for 3 months) or to ethinyl estradiol (35 microg)-cyproterone acetate (2 mg) oral contraceptive pills (Diane Nova) for 6 months. Metformin significantly decreased the waist-to-hip ratio, serum testosterone, fasting free fatty acid, and insulin concentrations and improved oxidative glucose utilization and menstrual cyclicity, with slight (but nonsignificant) improvements in insulin hepatic extraction and insulin sensitivity. Diane Nova significantly decreased serum testosterone and increased serum sex hormone-binding globulin concentrations and glucose area under the curve during oral glucose tolerance test. It is concluded that metformin, probably by way of its effect on adipose tissue, leads to reduction of hyperinsulinemia and concomitant improvement in the menstrual pattern; and therefore, it offers a useful alternative treatment for obese, anovulatory women with PCOS. Despite slight worsening of glucose tolerance, Diane Nova is an efficient treatment for women with hyperandrogenism and hirsutism.
BACKGROUND: Several studies have shown the efficacy of endocrine therapy in combination with radiotherapy in high-risk prostate cancer. To assess the effect of radiotherapy, we did an open phase III study comparing endocrine therapy with and without local radiotherapy, followed by castration on progression. METHODS: This randomised trial included men from 47 centres in Norway, Sweden, and Denmark. Between February, 1996, and December, 2002, 875 patients with locally advanced prostate cancer (T3; 78%; PSA
Comment In: Ann Intern Med. 2009 Jun 16;150(12):JC6-619528551
Comment In: Eur Urol. 2009 May;55(5):1239-40
Comment In: Eur Urol. 2009 May;55(5):1240
Comment In: Lancet. 2009 Jan 24;373(9660):274-619091392
Final results of the Canadian prospective phase II trial of intermittent androgen suppression for men in biochemical recurrence after radiotherapy for locally advanced prostate cancer: clinical parameters.
This prospective Phase II study was undertaken to evaluate intermittent androgen suppression as a form of therapy in men with localized prostate cancer who failed after they received external beam irradiation.
Patients who demonstrated a rising serum prostate-specific antigen (PSA) level after they received radiotherapy and who were without evidence of distant metastasis were accepted into the study. Treatment in each cycle consisted of cyproterone acetate given as lead-in therapy for 4 weeks, followed by a combination of leuprolide acetate and cyproterone acetate, which ended after a total of 36 weeks.
Of 109 patients registered, 103 patients were eligible for interruption of treatment, yielding a PSA response rate of 95%. The study continued for 6 years with a mean follow-up of 3.7 years (median follow-up, 4.2 years). The time off treatment averaged 53% of the total cycle time but, in absolute terms, decreased with each succeeding cycle, ranging from 63.7 weeks in Cycle 1 to 25.6 weeks in Cycle 5. Prostate volume was reduced by 40% in Cycle 1 and by 34% in Cycle 2, and there were no decreases in Cycle 3 or Cycle 4. At the end of the trial, 38.5% of patients still were receiving treatment, 23.9% of patients had failed, and 15.6% of patients had died. Only 2% of deaths were cancer-specific.
Biochemical recurrence after irradiation for localized prostate cancer was amenable to cyclic androgen withdrawal therapy and showed a high response rate. Despite progressively shorter treatment cycles, the off-treatment interval remained appreciable, ranging from 65% in Cycle 1 to 46% in Cycle 5.