| 1. |
- Bjartell, Anders, et al.
(författare)
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Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort
- 2016
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 50:4, s. 255-259
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer. Material and methods: The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c-T2, Gleason score 5-10, N0/NX, M0/MX, prostate-specific antigen (PSA)<20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan-Meier 1 year BCR. Results: The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population. Conclusions: This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram
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| 2. |
- Thomsen, Frederik B., et al.
(författare)
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Prognostic Implications of 2005 Gleason Grade Modification. Population-Based Study of Biochemical Recurrence Following Radical Prostatectomy
- 2016
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Ingår i: Journal of Surgical Oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 114:6, s. 664-670
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the impact of the 2005 modification of the Gleason classification on risk of biochemical recurrence (BCR) after radical prostatectomy (RP). Patients and Methods: In the Prostate Cancer data Base Sweden (PCBaSe), 2,574 men assessed with the original Gleason classification and 1,890 men assessed with the modified Gleason classification, diagnosed between 2003 and 2007, underwent primary RP. Histopathology was reported according to the Gleason Grading Groups (GGG): GGG1 = Gleason score (GS) 6, GGG2 = GS 7(3+4), GGG3 = GS 7(4+3), GGG4 = GS 8 and GGG5 = GS 9-10. Cumulative incidence and multivariable Cox proportional hazards regression models were used to assess difference in BCR. Results: The cumulative incidence of BCR was lower using the modified compared to the original classification: GGG2 (16% vs. 23%), GGG3 (21% vs. 35%) and GGG4 (18% vs. 34%), respectively. Risk of BCR was lower for modified versus original classification, GGG2 Hazard ratio (HR) 0.66, (95% CI 0.49-0.88), GGG3 HR 0.57 (95% CI 0.38-0.88) and GGG4 HR 0.53 (95% CI 0.29-0.94). Conclusion: Due to grade migration following the 2005 Gleason modification, outcome after RP are more favourable. Consequently, outcomes from historical studies cannot directly be applied to a contemporary setting.
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| 3. |
- Fridriksson, Jón O., et al.
(författare)
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Long-term adverse effects after curative radiotherapy and radical prostatectomy : population-based nationwide register study
- 2016
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 50:5, s. 338-345
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to assess the risk of serious adverse effects after radiotherapy (RT) with curative intention and radical prostatectomy (RP). Materials and methods: Men who were diagnosed with prostate cancer between 1997 and 2012 and underwent curative treatment were selected from the Prostate Cancer data Base Sweden. For each included man, five prostate cancer-free controls, matched for birth year and county of residency, were randomly selected. In total, 12,534 men underwent RT, 24,886 underwent RP and 186,624 were controls. Adverse effects were defined according to surgical and diagnostic codes in the National Patient Registry. The relative risk (RR) of adverse effects up to 12 years after treatment was compared to controls and the risk was subsequently compared between RT and RP in multivariable analyses. Results: Men with intermediate- and localized high-risk cancer who underwent curative treatment had an increased risk of adverse effects during the full study period compared to controls: the RR of undergoing a procedures after RT was 2.64 [95% confidence interval (CI) 2.56–2.73] and after RP 2.05 (95% CI 2.00–2.10). The risk remained elevated 10–12 years after treatment. For all risk categories of prostate cancer, the risk of surgical procedures for urinary incontinence was higher after RP (RR 23.64, 95% CI 11.71–47.74), whereas risk of other procedures on the lower urinary tract and gastrointestinal tract or abdominal wall was higher after RT (RR 1.67, 95% CI 1.44–1.94, and RR 1.86, 95% CI 1.70–2.02, respectively). Conclusion: The risk of serious adverse effects after curative treatment for prostate cancer remained significantly elevated up to 12 years after treatment.
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| 4. |
- Loeb, Stacy, et al.
(författare)
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Use of Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction and Risk of Malignant Melanoma
- 2015
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 313:24, s. 2449-2455
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The target for the oral erectile dysfunction drugs, phosphodiesterase type 5 (PDE5) inhibitors, is part of a pathway implicated in the development of malignant melanoma. An increased risk of melanoma in sildenafil users was recently reported. OBJECTIVE To examine the association between use of PDE5 inhibitors and melanoma risk, including data on specific PDE5 inhibitors, number of prescriptions, and melanoma stage. DESIGN, SETTING, AND PARTICIPANTS Nationwide, population-based, nested case-control study in the Swedish Prescribed Drug Register, the Swedish Melanoma Register, and other health care registers and demographic databases in Sweden, including 4065 melanoma cases diagnosed from 2006 through 2012 and 5 randomly selected controls per case with matching year of birth. EXPOSURES Number of filled prescriptions for the PDE5 inhibitors sildenafil and vardenafil or tadalafil. MAIN OUTCOMES AND MEASURES Risk of melanoma; overall and by stage and risk of basal cell carcinoma in multivariable logistic regression analyses. RESULTS Of 4065 melanoma cases, 435 men (11%) had filled prescriptions for PDE5 inhibitors, as did 1713 men of 20 325 controls (8%). In multivariable analysis, there was an increased risk of melanoma in men taking PDE5 inhibitors (OR, 1.21 [95% CI, 1.08-1.36]). The most pronounced increase in risk was observed in men who had filled a single prescription (OR, 1.32 [95% CI, 1.10-1.59]; exposure rate, 4% for cases vs 3% for controls), but was not significant among men with multiple filled prescriptions (for 2-5 prescriptions: OR, 1.14 [95% CI, 0.95-1.37], 4% for cases and 3% for controls; for >= 6 prescriptions: OR, 1.17 [95% CI, 0.95-1.44], 3% for cases vs 2% for controls). PDE5 inhibitors were significantly associated with melanoma stage 0 (OR, 1.49 [95% CI, 1.22-1.83], 13% for cases vs 8% for controls) and stage I (OR, 1.21 [95% CI, 1.02-1.43], 12% for cases vs 10% for controls), but not stage II through IV (OR, 0.83 [95% CI, 0.63-1.09], 6% for cases vs 7% for controls). The risk estimates were similar for sildenafil and vardenafil or tadalafil. PDE5 inhibitor use was also associated with an increased risk of basal cell carcinoma (OR, 1.19 [95% CI, 1.14-1.25], 9% for cases vs 8% for controls). Men taking PDE5 inhibitors had a higher educational level and annual income, factors that were also significantly associated with melanoma risk. CONCLUSIONS AND RELEVANCE In a Swedish cohort of men, the use of PDE5 inhibitors was associated with a modest but statistically significant increased risk of malignant melanoma. However, the pattern of association (eg, the lack of association with multiple filled prescriptions) raises questions about whether this association is causal.
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| 5. |
- Thomsen, Frederik Birkebaek, et al.
(författare)
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Anti-androgen monotherapy versus gonadotropin-releasing hormone agonists in men with advanced, non-metastatic prostate cancer : a register-based, observational study
- 2019
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 58:1, s. 110-118
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Tidskriftsartikel (refereegranskat)abstract
- Background:In randomised controlled trials, men with advanced, non-metastatic prostate cancer (PCa) treated with anti-androgen monotherapy (AA) had similar all-cause mortality as men treated with gonadotropin-releasing hormone (GnRH) agonists. Using real-world evidence (i.e., observational data), we aimed to further assess the difference in mortality between these two drug categories.Material and Methods:We emulated a trial using data from Prostate Cancer data Base Sweden 3.0. We specifically focused on men diagnosed in 2006-2012 with high-risk PCa who had no distant metastasis. They either received primary hormonal therapy with AA (n=2078) or GnRH agonists (n=4878) who were followed for a median time of 5 years. Risk of death from PCa and other causes was assessed using competing risk analyses and Cox proportional hazards regression analyses, including propensity score matching.Results:The cumulative 5-year PCa mortality was lower for men treated with AA (16% [95% confidence interval, CI, 15-18%]) than men treated with GnRH agonists (22% [95% CI 21-24%]). The 5-year other cause mortality was also lower for men on AA (17% [95% CI 15-19%] compared to men on GnRH agonists (27% [95% CI 25-28%]). In regression analyses, the risk of PCa death was similar, GnRH agonists versus AA (reference), hazard ratio (HR) 1.08 (95% CI 0.95-1.23), but the risk of death from all causes was higher for men on GnRH agonists, HR 1.23 (95% CI 1.13-1.34). Consistent results were seen in the propensity score-matched cohort.Conclusion:Our results indicate that the use of AA as primary hormonal therapy in men with high-risk non-metastatic PCa does not increase PCa-specific mortality compared to GnRH. Using AA instead of GnRH agonists may result in shorter time on/exposure to GnRH-treatment, which may reduce the risk of adverse events associated with this treatment.
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| 6. |
- Lycken, Magdalena, et al.
(författare)
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The use of palliative medications before death from prostate cancer: Swedish population-based study with a comparative overview of European data
- 2018
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 88, s. 101-108
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Tidskriftsartikel (refereegranskat)abstract
- Background: Symptoms of terminal cancer have previously been reported as under-treated. The aim of this study was to assess the use of palliative medications before death from prostate cancer. Methods: This Swedish register study included men who died from 2009 to 2012 with prostate cancer as the underlying cause of death. We assessed the proportion who collected a prescription of androgen deprivation therapy, non-steroidal anti-inflammatory drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and sedative-hypnotics and the differences in treatment related to age, time since diagnosis, educational level, close relatives and comorbidities. Data were collected from 3 years before death from prostate cancer. Results: We included 8326 men. The proportion who received opioids increased from 30% to 72% during the last year of life, and 67% received a strong opioid at the time of death. Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and sedative-hypnotics from 21% to 33%. Men without close relatives and older men had lower probability to receive opioids (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.47-0.66 for > 85 years versus < 70 years) and (OR 0.78, 95% CI: 0.66-0.92 for unmarried without children versus married with children). Conclusion: Our results represent robust epidemiological data from Sweden for comparison of palliative care quality between countries. The findings indicate that men without close relatives and older men are disadvantaged with respect to the treatment of cancer pain and need closer attention from health care providers and highlight the importance to identify psychological distress in terminal prostate cancer. (C) 2017 Elsevier Ltd. All rights reserved.
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| 7. |
- Tomic, Katarina, et al.
(författare)
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Evaluation of data quality in the National Prostate Cancer Register of Sweden
- 2015
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 51:1, s. 101-111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Data in cancer quality registers are increasingly used for quality assurance, benchmarking, and research. MATERIALS AND METHODS: Data in the National Prostate Cancer Register (NPCR) of Sweden were evaluated for completeness, timeliness, comparability and validity. Completeness and timeliness were assessed by cross-linkage to the Swedish Cancer Register, comparability was examined by comparing registration routines in NPCR with national and international guidelines, and validity was assessed by re-abstraction of data from medical charts for 731 men diagnosed with prostate cancer (Pca) in 2009. Furthermore, data on treatment were validated by record linkage to the Swedish Patient Register and The Prescribed Drug Register. RESULTS: NPCR captured 98% of Pca cases in the Cancer Register and the mean value for completeness of the 48 evaluated variables was 90% (range 64-100%). Timeliness increased substantially from 2008 to 2012 with 95% of cases reported within 12months after diagnosis in 2012. NPCR complied with national and international coding routines. Overall, the agreement between original data and re-abstracted data from 731 charts was high. For example, the correlation between original and re-abstracted data was 1.00 for date of surgery, and 0.97 for serum levels of prostate specific antigen and exact agreement was 97% for Gleason score at biopsy, 83% for clinical local T stage and more than 95% of the androgen deprivation therapies registered in NPCR had a corresponding filled prescription. CONCLUSION: Record linkages with other data sources and re-abstraction of data showed that data quality in NPCR is high.
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| 8. |
- Fridriksson, Jon Örn, et al.
(författare)
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Long-term adverse effects after retropubic and robot-assisted radical prostatectomy : Nationwide, population-based study
- 2017
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Ingår i: Journal of Surgical Oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 116:4, s. 500-506
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Surgery for prostate cancer is associated with adverse effects. We studied long-term risk of adverse effects after retropubic (RRP) and robot-assisted radical prostatectomy (RARP).Methods: In the National Prostate Cancer Register of Sweden, men who had undergone radical prostatectomy (RP) between 2004 and 2014 were identified. Diagnoses and procedures indicating adverse postoperative effects were retrieved from the National Patient Register. Relative risk (RR) of adverse effects after RARP versus RRP was calculated in multivariable analyses adjusting for year of surgery, hospital surgical volume, T stage, Gleason grade, PSA level at diagnosis, patient age, comorbidity, and educational level.Results: A total of 11 212 men underwent RRP and 8500 RARP. Risk of anastomotic stricture was lower after RARP than RRP, RR for diagnoses 0.51 (95%CI = 0.42-0.63) and RR for procedures 0.46 (95%CI = 0.38-0.55). Risk of inguinal hernia was similar after RARP and RRP but risk of incisional hernia was higher after RARP, RR for diagnoses 1.48 (95%CI = 1.01-2.16), and RR for procedures 1.52 (95%CI = 1.02-2.26).Conclusions: The postoperative risk profile for RARP and RRP was quite similar. However, risk of anastomotic stricture was lower and risk of incisional hernia higher after RARP.
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| 9. |
- Sverrisson, Ingvar, et al.
(författare)
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Anastomotic leakage after anterior resection in patients with rectal cancer previously irradiated for prostate cancer
- 2019
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 45:3, s. 341-346
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:There are little data on the post-operative outcome of anterior resection (AR) for rectal cancer in men who had received radiotherapy for prostate cancer previously. The aim of this study was to assess the rate of anastomotic leakage (AL) after AR in these patients.Methods:All men who underwent bowel resection because of rectal cancer between 2000 and 2016 and had been diagnosed previously with prostate cancer were identified by linking the Swedish Colorectal Cancer Registry with the National Prostate Cancer Register. The medical records of men who underwent AR and had previously received radiotherapy for prostate cancer were reviewed.Results:In total, 13299 men had undergone a bowel resection for rectal cancer, 188 of whom had previously received radiotherapy for prostate cancer. Among those who had received radiation therapy, 59 men (31%) had an AR: 50 men (85%) received a diverting ileostomy, 42 men (71%) had an American Society of Anesthesiologists score of 1-2 and 36 men (61%) had tumour stage 1-2. AL was found in 12/59 men (20%), one of whom had a re-laparotomy. There was no 90-day mortality.Conclusions:In the combined national population-based registries, a minority of patients with rectal cancer had an AR after previous radiotherapy for prostate cancer. These patients were healthy with early cancer stages and, in this selected group of patients, the AL rate was much lower than that reported previously.
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| 10. |
- Adamo, Hanibal Hani, 1984-, et al.
(författare)
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Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome
- 2019
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Ingår i: The Prostate. - : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 79:5, s. 435-445
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Tidskriftsartikel (refereegranskat)abstract
- Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.
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