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ABSTRACT: The objective of this study was to investigate standardised relative survival and mortality ratio for patients undergoing radical prostatectomy for localized prostate cancer at our institution.
Between 1995 and 2010, a total of 1,350 consecutive patients underwent radical prostatectomy. Patients were followed prospectively per protocol. No patients were lost to follow-up. Overall and cause-specific survival were described using Kaplan-Meier plots. Standardized relative survival and mortality ratio were calculated based on expected survival in the age-matched Danish population using the methods and macros described by Dickmann. The country-specific population mortality rates used for calculation of the expected survival were based on data from The Human Mortality Database.
The median follow-up was 3.4 years (range: 0-14.3 years). A total of 59 (4.4%) patients died during follow-up. In all, 17 (1.3%) patients died of prostate cancer. The estimated ten-year overall survival was 89.3%. The cancer-specific survival was estimated to 96.6% after ten years. Relative survival was 1.04 after five years and 1.14 after ten years. The standardized mortality ratio, i.e. observed mortality/expected mortality, was 0.61 and 0.39 at five and ten years, respectively.
The overall and cancer-specific ten-year survival in a consecutive series of patients in a non-screened Danish population is ≥ 89%. The survival and mortality ratio is significantly better than expected in the age-matched background population. This finding is likely explained by selection bias. Although the results indicate an excellent outcome in terms of cancer control, the efficacy of prostatectomy for localized prostate cancer remains at debate.
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Danish medical journal. 04/2013; 60(4):A4612.
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ABSTRACT: OBJECTIVES: To describe survival and cause of death in a nationwide cohort of Danish patients with prostate cancer undergoing radical prostatectomy (RP). To describe risk factors associated with prostate cancer mortality. PATIENTS AND METHODS: Observational study of 6489 men with localised prostate cancer treated with RP at six different hospitals in Denmark between 1995 and 2011. Survival was described using Kaplan-Meier estimates. Causes of death were obtained from the national registry and cross-checked with patient files. Cumulative incidence of death, any cause and prostate cancer-specific, was described using Nelson-Aalen estimates. Risk for prostate cancer death was analysed in a Cox multivariate regression model using the covariates: age, cT-category, PSA level and biopsy Gleason score. RESULTS: The median follow-up was 4 years. During follow-up, 328 patients died, 109 (33.2%) from prostate cancer and 219 (66.8%) from other causes. Six patients (0.09%) died ≤30 days of RP. In multivariate analysis, cT-category was a predictor of prostate cancer death (P < 0.001). Compared with T1 disease, both cT2c (hazard ratio [HR] 2.2) and cT3 (HR 7.2) significantly increased the risk of prostate cancer death. For every doubling of PSA level the risk of prostate cancer death was increased by 34.8% (P < 0.001). Biopsy Gleason score 4 + 3 and ≥8 were associated with an increased risk of prostate cancer death compared with biopsy Gleason score ≤ 6 of 2.3 and 2.7 (P = 0.003), respectively. The cumulative hazard of all-cause and prostate cancer-specific mortality after 10 years was 15.4% (95% confide3nce interval [CI] 13.2-17.7) and 6.6% (95% CI 4.9-8.2) respectively. CONCLUSIONS: We present the first survival analysis of a complete, nationwide cohort of men undergoing RP for localised prostate cancer. The main limitation of the study was the relatively short follow-up. Interestingly, our national results are comparable to high-volume, single institution, single surgeon series.
BJU International 03/2013; · 2.84 Impact Factor
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ABSTRACT: The incidence of prostate cancer in Denmark rose approximately 50% from 2000 to 2009 in parallel with the introduction of prostate-specific antigen (PSA)-testing. Available evidence indicates a significant overtreatment of patients with low-risk prostate cancer. Active surveillance has been proposed as an observation strategy to reduce overtreatment and limit curatively intended therapy to those patients who need it. We reported the first Danish results from an active surveillance cohort.
A total of 167 patients were prospectively followed in an active surveillance programme.
The median follow-up was 3.4 years (1.1-9.5). At entry the median age was 65 years (51-73), 94% had a Gleason score ≤ 6, 87.4% had a PSA ≤ 10 ng/ml and 99% ≤ cT2a. Ten patients progressed on digital rectal examination, 40 patients progressed due to a short PSA doubling time, and 34 patients progressed on re-biopsy. A total of 59 patients discontinued active surveillance. The estimated five-year probability of remaining on active surveillance was 60.0% (95% confidence interval 50.9-69.1%).
Active surveillance as a management strategy for patients with clinically localized, low-risk prostate cancer is accepted by patients, seems feasible and can reduce overtreatment. However, long-term follow-up data are lacking and considerable uncertainties about optimal selection and progression criteria remain.
The authors received financial support from the IMK Almene Fond.
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Danish medical journal. 02/2013; 60(2):A4575.
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ABSTRACT: There is no evidence for the use of radical prostatectomy in patients with disseminated prostate cancer. However, development of new and effective treatment strategies has changed the therapeutic scenario for advanced disease. Multimodal therapy, also including local therapy of the primary tumour, has received increased attention, and clinical studies in lymph node positive disease are under way. We report three patients in whom radical prostatectomy was performed despite the presence of metastases.
Ugeskrift for laeger 12/2012; 174(50):3160-3161.
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ABSTRACT: Abstract Objective. The aim of this study was to evaluate the impact of preoperative and surgical parameters, including nerve-sparing technique, on the risk of positive surgical margins (PSM) following radical prostatectomy for clinically localized prostate cancer. Material and methods. A prospective consecutive single-institution Danish cohort of 1148 patients undergoing RP between 1995 and 2011 was investigated. To analyse the impact of covariates on risk of PSM, a multivariate logistic regression model was used, including cT category, biopsy Gleason score, prostate-specific antigen (PSA), percentage positive biopsies for cancer (PPB), surgeon and surgical technique. Results. The overall rate of PSM was 31.4%. The risk of PSM depended (p value for Wald χ (2) ) on PSA (p < 0.0001), PPB (p = 0.003), nerve-sparing surgery (p = 0.03) and the surgeon (p < 0.0001). For every doubling of PSA, the risk of PSM increased by 56%, beginning at 0.5 ng/ml [odds ratio (OR) = 1.56, 95% confidence interval (CI) 1.3-1.9, p < 0.01], and every 10% increase in PPB resulted in an 11% increased risk of PSM (OR = 1.11, 95% CI 1.0-1.2, p = 0.002). Two out of the six surgeons had a 50% reduction of risk of PSM compared to the referent surgeon. Nerve-sparing surgery increased the risk of PSM by 50% compared to wide resection (OR = 1.5, 95% CI 1.0-2.1, p = 0.03). Conclusion: Both preoperative and surgical parameters affect the risk of PSM after radical prostatectomy. Surgeon and high preoperative PSA, PPB and cT category were confirmed as predictors of PSM. Surprisingly, nerve-sparing surgery was independently associated with increased risk of PSM. The correct selection of candidates for nerve-sparing surgery remains unresolved.
Scandinavian Journal of Urology and Nephrology 11/2012; · 0.99 Impact Factor
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ABSTRACT: In an attempt to minimize overtreatment of localized prostate cancer (PCa) active surveillance (AS) and minor invasive procedures have received increased attention. We investigated the accuracy of pre-operative findings in defining insignificant disease and distinguishing between unilateral/unifocal and bilateral/multifocal PCa. One-hundred and sixty patients undergoing radical prostatectomy were included. Histology reports from the biopsies and matching prostatectomies were compared. Three definitions of insignificant cancer were used: InsigE: tumour volume ≤0.5 mL; InsigW: tumour volume ≤1.3 mL; InsigM: tumour ≤5% of total prostate volume and prostate-specific antigen (PSA) ≤10 ng/mL. In all definitions, Gleason score (GS) was ≤6 and the tumour was organ confined. Biopsies alone performed poorly as a predictor of unifocal and unilateral cancer in the prostatectomy specimens with positive predictive values of 17.8% and 18.9% respectively. Inclusion of other clinical and biochemical parameters did not significantly increase the predictive value. However, the combination of GS ≤ 6, PSA ≤ 10 ng/mL and unifocal or unilateral cancer in biopsy cores resulted in a positive predictive value of 61.1%, 38.9% and 12.0%, respectively, for identifying InsigM, InsigW and InsigE in the prostate specimen. Conclusively, routine prostate biopsies cannot predict unifocal and unilateral PCa, and must be regarded insufficient to select patients for focal therapy. Although candidates for AS may be identified using standard biopsies, a considerable fraction of patients will be understaged. There is a need for more precise diagnostic tools to assess intraprostatic tumour growth.
Apmis 08/2012; · 1.99 Impact Factor
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ABSTRACT: Abstract Objective. The optimal therapeutic strategy for high-risk localized prostate cancer (PCa) is controversial. Supported by randomized trials, the combination of external beam radiation therapy (EBRT) and endocrine therapy (ET) is advocated by many, while radical prostatectomy (RP) is regarded as primary therapy by others. This study examined the outcome for high-risk localized PCa patients treated with RP. Material and methods. Of 1300 patients who underwent RP, 231 were identified as high-risk. Patients were followed for biochemical recurrence (BCR) (defined as prostate-specific antigen ≥ 0.2 ng/ml), metastatic disease and survival. Excluding node-positive patients, none of the patients received adjuvant therapy before BCR was confirmed. Univariate and multivariate analysis was performed with Kaplan-Meier and Cox proportional hazard models. Results. Median follow-up was 4.4 years (range:0.1-14.9). The estimated 10-year biochemical recurrence-free survival was 49%, 10-year metastasis-free survival was 81%, 10-year overall survival was 84% and estimated cause-specific survival after 10 years was 90%. In multivariate analysis extracapsular extension, seminal vesicle invasion and young age were significant predictors of BCR. Conclusion. The results confirm that a significant proportion of patients with high-risk PCa remain biochemically diseasefree and without a need for ET following RP as the primary and only treatment. A large randomized study of RP as primary therapeutic strategy versus the combination of EBRT and ET in patients with high-risk localized PCa seems warranted.
Scandinavian Journal of Urology and Nephrology 07/2012; · 0.99 Impact Factor
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ABSTRACT: To investigate the effects of baseline testosterone on testosterone control and prostate-specific antigen (PSA) suppression using data from a phase III trial (CS21) comparing degarelix and leuprolide in prostate cancer.
In CS21, patients with histologically confirmed prostate cancer (all stages) were randomized to degarelix 240 mg for 1 month followed by monthly maintenance doses of 80 or 160 mg, or leuprolide 7.5 mg/month. Patients receiving leuprolide could receive antiandrogens for flare protection. Treatment effects on testosterone and PSA reduction, testosterone surge, and microsurges were investigated in 3 baseline testosterone subgroups: <3.5, 3.5-5.0, and >5.0 ng/mL. Data are presented for the groups receiving degarelix 240/80 mg (the approved dose) and leuprolide 7.5 mg.
Higher baseline testosterone delayed castration with both treatments. However, castrate testosterone levels and PSA suppression occurred more rapidly with degarelix irrespective of baseline testosterone. With leuprolide, the magnitude of testosterone surge and microsurges increased with increasing baseline testosterone. There was no overall correlation between baseline testosterone and initial PSA decrease in either treatment group, although PSA suppression tended to be slowest with leuprolide and fastest with degarelix in the high baseline testosterone subgroup.
Patients with high baseline testosterone may have greater risk of tumor stimulation (clinical flare) and mini-flares during gonadotrophin-releasing hormone agonist treatment and so the need for flare protection with antiandrogens in these patients is obvious, especially in metastatic disease. Although higher baseline testosterone delays castration, castrate testosterone and PSA suppression occur more rapidly with degarelix, irrespective of baseline testosterone, without the need for flare protection.
Urology 07/2012; 80(1):174-80. · 2.43 Impact Factor
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ABSTRACT: This study aimed to investigate the impact of positive surgical margins (PSMs), stratified by location and extension, on biochemical outcome after radical retropubic prostatectomy (RRP).
The study included data from 605 consecutive patients treated with RRP for localized prostate cancer. Patients with node-positive disease were excluded. Biochemical recurrence-free survival was calculated using the Kaplan-Meier method. Univariate and multivariate analysis was used to assess risk factors.
The overall PSM rate was 35.4%. Eighty-three per cent (82.7%) of these had a single PSM, whereas 17.3% of patients had two or more PSMs. Apical PSMs were present in 42.5% and non-apical in 57.5%. The presence of any PSM had a significant impact on the risk of biochemical recurrence (BR) [hazard ratio (HR) = 3.3, p < 0.0001]. Compared with margin-negative patients, both apical and non-apical PSMs increased the risk of BR (HR = 2.1 and 4.2, p = 0.02 and p < 0.0001, respectively). The number of PSMs also influenced the risk of BR (one PSM: HR = 2.8, p < 0.0001, vs two or more PSMs: HR = 5.5, p < 0.0001). In multivariate analysis, pT category, PSA and prostatectomy Gleason score independently increased the risk of BR. In an exploratory multivariate analysis of pT2 tumours, the impact of apical PSMs on biochemical recurrence-free survival (BRFS) was not statistically significant, although with an HR of 2.1. Non-apical PSM was associated with a significantly increased risk of BR (HR = 3.4, p = 0.01). Number of PSMs did not influence the risk of BR in multivariate analysis.
The presence of PSMs after RRP is associated with a higher risk of BR. Multiple and non-apical PSMs are associated with a significantly higher risk of BR compared to single and apical PSMs.
Scandinavian Journal of Urology and Nephrology 02/2012; 46(3):172-9. · 0.99 Impact Factor
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ABSTRACT: • To investigate serum testosterone levels as a predictor for biochemical failure (BF) after radical retropubic prostatectomy (RRP).
• Prospective cohort study with 227 patients and a median follow-up of 7.7 years. • Total serum testosterone was measured at diagnosis. • Primary endpoint: 5-year BF-free survival defined as first PSA > 0.2 ng/mL. • Testosterone was tested as a predictor of BF as a dichotomized and continuous variable.
• Median (range) age was 62 years (45-74), median PSA 9.9 ng/mL (0.4-96), and median testosterone was 14 nmol/L (2.2-40). • BF occurred for 57 patients (26%) within 5 years. • In multivariate analysis with age, PSA, and biopsy Gleason score, testosterone levels >11 nmol/L were an independent predictor for reduced risk of BF (hazard ratio, 0.53; 95% confidence interval, 0.31-0.90; P= 0.02). • When analyzed as a continuous variable, testosterone was not a statistically significant predictor of BF.
• Low pretreatment serum testosterone levels correlate with a higher risk of BF, and testosterone may possess biological information about prostate cancer progression potential, which makes it an independent predictor of biochemical failure after RRP.
BJU International 08/2011; 109(4):520-4. · 2.84 Impact Factor
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Ugeskrift for laeger 06/2011; 173(25):1783.
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Ugeskrift for laeger 06/2011; 173(24):1748; author reply 1748.
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ABSTRACT: The purpose of this study was to investigate the prognostic value of different forms of the urokinase receptor, uPAR, in serum from prostate cancer (PC) patients.
The uPAR forms were measured in samples from 131 metastatic PC patients. These constituted a subset of patients included in a randomized clinical trial of treatment with total androgen blockade (TAB) versus polyestradiol phosphate (PEP). Pre-treatment serum levels of intact uPAR (uPAR(I-III)), intact plus cleaved uPAR (uPAR(I-III) + uPAR(II-III)) and domain I (uPAR(I)) were measured using time-resolved fluorescence immunoassays (TR-FIAs).
High serum levels of each of the uPAR forms were significantly associated with short overall survival (OS). The prognostic impact was strongest in the TAB treated patients with all uPAR forms being statistically significant. In multivariate analysis, uPAR(I-III) + uPAR(II-III) was an independent prognostic factor in TAB treated patients (HR = 5.2, 95% confidence interval (CI): 2.5-10.6, P < 0.0001) but not in PEP treated patients (P = 0.40). In the entire study population, OS was similar in the two treatment groups. The survival analysis showed significant interactions between treatment modality and the level of either uPAR(I-III) or uPAR(I-III) + uPAR(II-III). High levels of uPAR(I-III) + uPAR(II-III) were found to be predictive of effect of PEP versus TAB treatment. Patients with uPAR(I-III) + uPAR(II-III) levels above the median had significantly longer OS (median difference 11.3 months), if treated with PEP rather than with TAB (HR = 1.8, 95% CI:1.1-3.1, P = 0.03).
uPAR forms are significantly associated with OS. High uPAR(I-III) + uPAR(II-III) predicts longer OS in patients treated with PEP compared to TAB. uPAR forms are promising prognostic and predictive markers in PC.
The Prostate 06/2011; 71(8):899-907. · 3.48 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
Scandinavian Journal of Urology and Nephrology 05/2011; 45(5):346-53. · 0.99 Impact Factor
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Ugeskrift for laeger 04/2011; 173(14):1080; author reply 1080.
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ABSTRACT: Histopathological grading of prostate cancer (PCa) is associated with significant interobserver variability. This, as well as clinical consequences of histopathological re-evaluation, was investigated. In 350 patients, histopathological re-evaluations of prostate biopsies were compared with primary pathology reports and with histopathology of the radical prostatectomy specimen. The consequences of re-evaluation for clinical workup and treatment of patients according to local algorithms were determined. For Gleason score (GS), complete agreement between primary report and re-evaluation was found in 76.9%. The cancers were assessed with higher GS at re-evaluation in 25.0% of patients in cases with primary GS ≤ 6, while scores were devaluated in 3.0% and 10.3% of the patients with primary GS = 7 and ≥ 8, respectively. Strategies for clinical evaluation and treatment were changed as a result of the biopsy re-evaluations in 19.7% and 13.1% of patients, respectively. Gleason scoring based on the radical prostatectomy specimen was higher than in both primary reports and re-evaluation of biopsies. Although a relatively high degree of concordance was found between biopsy assessments, the significant trend towards higher Gleason scoring at re-evaluation, leading to frequent changes in clinical assessments and surgical strategy, justifies re-evaluation of PCa biopsies in patients with primary GS ≤ 6.
Apmis 04/2011; 119(4-5):239-46. · 1.99 Impact Factor
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Ugeskrift for laeger 02/2011; 173(9):677; author reply 677.
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ABSTRACT: Radical retropubic prostatectomy (RRP) as intended curative therapy for patients with clinically localized prostate cancer (PC) was initiated in 1995 in Denmark. This paper reports single-institution results from the first 1200 consecutive patients operated during a 15-year period. Median age at surgery was 63 years. Median PSA was 9 ng/mL. Palpable tumors (≤cT2) were present in 48% of patients. Gleason score at biopsy was ≤7 for 85% of patients. In sixty-five percent of patients, histopathology revealed localized PCa after RRP. Positive surgical margins were found in 39.2% of the cases. Biochemical recurrence (BR) occurred for 214 (18%) of patients. The estimated biochemical recurrence free survival (BRFS) was 71.7% and 63.2% after 5 and 10 years, respectively. When patients were stratified according to the D'Amico criteria, BRFS after 10 years was 75.3%, 59.7%, and 39.3% for low-, medium- and high-risk patients, respectively. In univariate analysis, clinical stage, PSA at diagnosis and type of surgery were significant predictors of BR. In multivariate analysis, Gleason score > 7, PSA > 10, and higher clinical stage were significant predictors of BR. Early Danish results in a population not subjected to screening demonstrate BRFS rates comparable with earlier reports from the prescreening era.
Prostate cancer. 01/2011; 2011:236357.
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ABSTRACT: To evaluate the efficacy and tolerability of bicalutamide 150 mg once-daily as immediate hormonal therapy in patients with prostate cancer or as adjuvant to radical prostatectomy or radiotherapy.
In all, 8113 patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N+) prostate cancer (all M0) were enrolled in three complementary, double-blind, placebo-controlled trials. Patients were randomized to receive standard care plus either oral bicalutamide 150 mg once-daily or oral placebo. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collated from individual trials and evaluated in a combined analysis.
Overall, at a median follow-up of 9.7 years, bicalutamide significantly improved PFS (hazard ratio 0.85, 95% confidence interval 0.79-0.91; P= 0.001). Compared with placebo there was no difference in OS (hazard ratio 1.01, P= 0.77). Patients who derived benefit from bicalutamide in terms of PFS were those with locally advanced disease, with OS significantly favouring bicalutamide in patients with locally advanced disease undergoing radiotherapy (P= 0.031). Patients with localized disease showed no clinically or statistically significant improvements in PFS; there was a survival trend in favour of placebo in patients with localized disease undergoing watchful waiting (P= 0.054). The overall tolerability of bicalutamide was consistent with previous analyses, with breast pain (73.7%) and gynaecomastia (68.8%) the most frequently reported adverse events in patients randomized to bicalutamide.
Bicalutamide 150 mg, either as monotherapy or adjuvant to standard care, improved PFS in patients with locally advanced prostate cancer, but not in patients with localized disease. A pre-planned subset analysis showed a benefit for OS in patients with locally advanced disease undergoing radiotherapy. Bicalutamide 150 mg might represent an alternative for patients with locally advanced prostate cancer considering androgen-deprivation therapy.
BJU International 04/2010; 105(8):1074-81. · 2.84 Impact Factor
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ABSTRACT: The effect of Casodex (ICI 176,334), a new, once-daily, selective antiandrogen, given as 50 mg monotherapy, was compared with orchidectomy in a randomised, multicentre, open study in 376 patients with metastatic prostate cancer. At 3 months, PSA was reduced by 86% in the Casodex group and by 96% in the orchidectomy group. Treatment failed in 51 patients in the orchidectomy group and 66 showed a subjective response. Treatment failed in 86 patients treated with Casodex and 40 patients showed a subjective response. Patients treated with Casodex maintained their sexual interest better than those in the orchidectomy group. Median survival was significantly longer in the orchidectomy group. Casodex was well-tolerated. The most likely reason for the differences between the groups regarding time to treatment failure and survival is that the dose of Casodex was too small. Further studies with higher doses of Casodex are in progress.
02/2010; 30(2):93-98.
