| 1. |
- Bill-Axelson, Anna, et al.
(författare)
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Radical Prostatectomy or Watchful Waiting in Prostate Cancer-29-Year Follow-up
- 2018
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Ingår i: New England Journal of Medicine. - : Massachussetts Medical Society. - 0028-4793 .- 1533-4406. ; 379:24, s. 2319-2329
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term followup is sparse. METHODS We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model. RESULTS By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer). CONCLUSIONS Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer.
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| 2. |
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| 3. |
- Demichelis, F., et al.
(författare)
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TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort
- 2007
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Ingår i: Oncogene. - Basingstoke : Nature Publ. Group. - 0950-9232 .- 1476-5594. ; 26:31, s. 4596-4599
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Tidskriftsartikel (refereegranskat)abstract
- The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio=2.7, P<0.01, 95% confidence interval=1.3–5.8). Quantitative reverse-transcription–polymerase chain reaction demonstrated high estrogen-regulated gene (ERG) expression to be associated with TMPRSS2:ERG fusion (P<0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.
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| 4. |
- Ahlberg, M., et al.
(författare)
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Time without PSA recurrence after radical prostatectomy as a predictor of prostate cancer death
- 2022
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:Suppl. 1, s. S286-S286
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction & Objectives: Although surveillance after radical prostatectomy routinely includes repeated Prostate Specific Antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk for prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence 5 and 10 years after radical prostatectomy.Materials & Methods: Between 1989 and 1998, 14 urological centres in Scandinavia randomized patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial. Data was collected prospectively. All 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1 year from inclusion were eligible in our cohort. 4 patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6 weeks from surgery (n=3). We stratified by Gleason score (≤3+4=7 or ≥4+3=7), pathological tumour stage (pT2 or ≥pT3), and negative or positive surgical margins. We analysed the cumulative incidences and absolute differences in metastatic disease and prostate cancer death.Results: We analysed 302 patients with complete follow-up during a median of 18 years. Median preoperative PSA was 9.8 ng/ml and median age at inclusion was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score ≤3+4=7 and 57% among men with Gleason score ≥4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12% respectively. The long-term probabilities were higher for pT≥3 vs. pT2 and for positive vs. negative surgical margins.Conclusions: Following radical prostatectomy, patients with Gleason score ≤3+4=7 without biochemical recurrence 5 years after radical prostatectomy had low risk of metastases and prostate cancer death independent of pT-stage and surgical margins. The risk of clinical progression decreased drastically the first 3 years after radical prostatectomy and after 10 years without biochemical recurrence, no patient was diagnosed with metastases or died from prostate cancer. Our study indicates that men with favourable histopathology without biochemical recurrence 5 years after radical prostatectomy can stop follow-up earlier than 10 years after radical prostatectomy while men with adverse pathology should continue with at least 10 years follow-up
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| 5. |
- Andrén, Lennart, 1946, et al.
(författare)
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Diltiazem in hypertensive patients with type II diabetes mellitus.
- 1988
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Ingår i: The American journal of cardiology. - : Elsevier BV. - 0002-9149. ; 62:11
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-three patients with essential hypertension and diabetes mellitus type II were treated with the calcium antagonist diltiazem (120 to 180 mg twice daily). The mean dose was 307 mg/day. The study was a double-blind, placebo-controlled, crossover design. All measurements were performed 12 to 14 hours after drug intake. Blood pressure, heart rate and forearm blood flow were measured noninvasively. Platelet function was studied by measuring adenosine diphosphate-induced platelet aggregation and the platelet specific proteins, beta thromboglobulin and platelet factor 4. Thromboxane B2 formation in serum and the plasma concentration of diltiazem and its metabolites N-demethyldiltiazem, deacetyldiltiazem and N-demethyldeacetyldiltiazem were measured both during placebo and diltiazem treatment. Diabetic control was evaluated by following HbA1C, fasting blood glucose and urinary glucose. Diltiazem reduced both systolic and diastolic (supine and standing) blood pressure significantly. Forearm blood flow was significantly increased by 32%, p less than 0.05. Supine heart rate decreased significantly, while no such change was seen in the standing position. No significant changes were observed in platelet function during diltiazem treatment. There was no relation between the observed blood pressure reduction and the plasma concentration of diltiazem or its metabolites. A positive correlation between the change in heart rate and the metabolite N-demethyldeacetyldiltiazem was observed (r = 0.647, p = 0.005). Three patients were excluded during diltiazem treatment (skin exanthema, headache and atrial fibrillation) and 1 during placebo treatment (angina pectoris). No negative effect on diabetes control was observed. Thus, diltiazem could be used for treatment of hypertension in diabetic patients.
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| 6. |
- Sadr-Azodi, O., et al.
(författare)
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Cigarette smoking, smoking cessation and acute pancreatitis : a prospective population-based study
- 2012
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Ingår i: Gut. - : BMJ PUBLISHING GROUP. - 0017-5749 .- 1468-3288. ; 61:2, s. 262-267
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Tidskriftsartikel (refereegranskat)abstract
- Background Several studies have shown that smoking increases the risk of chronic pancreatitis. However, the impact of smoking on the development of acute pancreatitis has not been fully studied. Objective To clarify the association between cigarette smoking, smoking cessation and the risk of acute pancreatitis. Design A follow-up study was conducted of 84 667 Swedish women and men, aged 46-84, during 12 years to study the association between smoking status, smoking intensity and duration, duration of smoking cessation and the risk of acute pancreatitis. Only those with the first event of the disease and no previous history of acute pancreatitis were included. Cox proportional hazards models were used to estimate rate ratios (RRs) with 95% CI for different smoking-related variables, adjusted for age, gender, body mass index, diabetes, educational level and alcohol consumption. Results In total, 307 cases with non-gallstone-related and 234 cases with gallstone-related acute pancreatitis were identified. The risk of non-gallstone-related acute pancreatitis was more than double (RR 2.29; 95% CI 1.63 to 3.22, p<0.01) among current smokers with >= 20 pack-years of smoking as compared with never-smokers. The corresponding risk among individuals with >= 400 g monthly consumption of alcohol was increased more than fourfold (RR=4.12; 95% CI 1.98 to 8.60, p<0.01). The duration of smoking rather than smoking intensity increased the risk of non-gallstone-related acute pancreatitis. After two decades of smoking cessation the risk of non-gallstone-related acute pancreatitis was reduced to a level comparable to that of non-smokers. There was no association between smoking and gallstone-related acute pancreatitis. Conclusion Smoking is an important risk factor for non-gallstone-related acute pancreatitis. Early smoking cessation should be recommended as a part of the clinical management of patients with acute pancreatitis.
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| 7. |
- Stattin, P., et al.
(författare)
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Geographical variation in incidence of prostate cancer in Sweden : Survey from the National Prostate Cancer Register
- 2005
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 39:5, s. 372-379
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate the geographical variation in prostate cancer incidence in Sweden, in particular the incidences of screening-detected tumours and curative treatment of prostate cancer. Material and methods. Data were retrieved from the National Prostate Cancer Register of Sweden for all cases of prostate cancer diagnosed in the year 2000-01. There were a total of 14376 cases of prostate cancer and the mean total annual age-adjusted incidence was 197/100000 men. There were 3318 cases in tumour category T1c, i.e. non-palpable tumours diagnosed during work-up for an elevated serum level of prostate-specific antigen, 1006 of which (30%) were asymptomatic and detected at a health check-up. Results. The difference between the counties with the lowest and highest age-adjusted incidences per 1OO 000 men of total prostate cancer was almost twofold (128 vs 217). The corresponding variation in incidence of category Tie tumours was more than fourfold (13 vs 60), the difference in incidence of Tie tumours detected in asymptomatic men was up to 10-fold (2 vs 20), and there was more than a fourfold variation in incidence of curative treatment between counties (13 vs 67). Measured incidences were mostly highest in urban regions and in counties with university hospitals. Conclusion. There are large geographical variations in prostate cancer incidence and in the frequency of curative treatment for prostate cancer in Sweden and there appear to be large geographical variations in the uptake of prostate cancer screening. © 2005 Taylor & Francis.
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| 8. |
- Andren, O., et al.
(författare)
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Cabazitaxel followed by androgen deprivation therapy (ADT) significantly improves time to progression in patients with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) : A randomized, open label, phase III, multicenter trial
- 2017
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Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 28:S5, s. v281-v281
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients with newly diagnosed mHSPC have a poor prognosis with a 3-year overall survival (OS) rate of 50%. Recently, combination of docetaxel (75mg/m2 every 6 weeks for 6 cycles) with ADT has become a new standard for such patients, based on results of 2 large phase 3 trials showing a significant OS benefit. In these trials, docetaxel was initiated within 3 months after ADT start. Timing of ADT and chemotherapy (CT) is controversial. In breast cancer, endocrine therapy is always started after CT, the rational being that ADT will turn clones of tumor cells in to a stage of dormancy where CT is less effective.Methods: This phase 3 trial randomized newly diagnosed mHSPC patients to receive cabazitaxel (CABA), 25 mg/m2 every 3 weeks for 10 cycles, followed by ADT (immediately after last CABA cycle) versus ADT alone. Primary end-point was OS. Secondary end-point was progression free survival. The study planned to include 400 patients but was closed prematurely due to low inclusion rate. A total 31 patients with newly diagnosed mHSPC were included and here we present the results.Results: Median follow up was 31 month. Of the CABA treated patients, 66.8% got six cycles or more and 46.7% completed all 10 courses. Median OS was 32,5 months with CABA followed by ADT and 29,5 months with ADT alone (HR 1.43, 95% CI 0.38-5.38). Median progression free survival was significantly longer in CABA treated patients (29 vs 12 months, HR 3.96 (95% CI 1.49-10.49). Main grade ≥ 3 toxicities were neutropenia (66%).Conclusions: In conclusion, results from this prematurely terminated trial suggest that CABA followed by ADT is effective in newly diagnosed mHSPC and shows a manageable toxicity. These results have to be validated in larger randomized trials.
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| 9. |
- Josefsson, Andreas, 1979, et al.
(författare)
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Effect of docetaxel added to bicalutamide in Hormone-Naive non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)
- 2023
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Ingår i: Acta Oncologica. - 0284-186X. ; 62:4, s. 372-380
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHistorically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS).Materials and MethodsPatients with hormone-naive, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m(2), q3w, 8-10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis.ResultsBetween 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0-5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50-0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49-0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse.ConclusionDocetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.
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| 10. |
- Penney, K. L., et al.
(författare)
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mRNA expression signature of Gleason grade predicts lethal prostate cancer
- 2011
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:17, s. 2391-2396
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis.PATIENTS AND METHODS: Using the complementary DNA-mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason ≤ 6 to those with Gleason ≥ 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases.RESULTS: We built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve [AUC] = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006).CONCLUSION: Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment.
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