| 1. |
- Berggren, Daniel Moreno, et al.
(författare)
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Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting : a report from the Swedish MDS register
- 2018
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 181:5, s. 614-627
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Tidskriftsartikel (refereegranskat)abstract
- The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population-based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population-based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) and the World Health Organization (WHO) Classification-based Prognostic Scoring System (WPSS). We also present population-based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy-related MDS (t-MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2.9 per 100000 inhabitants. IPSS-R had a significantly better prognostic power than IPSS (P < 0001). There was a trend for better prognostic power of IPSS-R compared to WPSS (P=0.05) and for WPSS compared to IPSS (P=0.07). IPSS-R was superior to both IPSS and WPSS for patients aged <= 70years. Patients with t-MDS had a worse outcome compared to de novo MDS (d-MDS), however, the validity of the prognostic scoring systems was comparable for d-MDS and t-MDS. In conclusion, population-based studies are important to validate prognostic scores in a real-world' setting. In our nationwide cohort, the IPSS-R showed the best predictive power.
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| 2. |
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| 3. |
- Björklund, Johan, et al.
(författare)
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Postoperative mortality 90 days after robot-assisted laparoscopic prostatectomy and retropubic radical prostatectomy : a nationwide population-based study
- 2016
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 118:2, s. 302-306
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess 90-day postoperative mortality after robot-assisted laparoscopic radical prostatectomy (RARP) and retropubic radical prostatectomy (RRP) using nationwide population-based registry data. Patients and Methods We conducted a cohort study using the National Prostate Cancer Register of Sweden, including 22 344 men with localized prostate cancer of clinical stage T1-T3, whose prostate-specific antigen levels were <50 mu g/mL and who had undergone primary radical prostatectomy in the period 1998-2012. Vital status was ascertained through the Total Population Register. The rates for 90-day postoperative mortality were analysed using logistic regression analysis, and comparisons of 90-day mortality with the background population were made using standardized mortality ratios (SMRs). Results Of the 14 820 men who underwent RRP, 29 (0.20%) died, and of the 7 524 men who underwent RARP, 10 (0.13%) died. Mortality in the cohort during the 90-day postoperative period was lower than in an age-matched background population: SMR 0.57 (95% confidence interval [CI] 0.39-0.75). There was no statistically significant difference in 90-day mortality according to surgical method: RARP vs RRP odds ratio (OR) 1.14; 95% CI 0.46-2.81. Postoperative 90-day mortality decreased over time: 2008-2012 vs 1998-2007 OR 0.44; 95% CI 0.21-0.95, mainly because of lower mortality after RARP. Conclusion The 90-day postoperative mortality rates were low after RARP and RRP and there was no statistically significant difference between the methods. Given the long life expectancy among men with low-and intermediate-risk prostate cancer, very low postoperative mortality is a prerequisite for RP, which was fulfilled by both RRP and RARP. The selection of healthy men for RP is highlighted by the lower 90-day mortality after RP compared with the background population.
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| 4. |
- Bratt, Ola, et al.
(författare)
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Undertreatment of Men in Their Seventies with High-risk Nonmetastatic Prostate Cancer
- 2015
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 68:1, s. 53-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many elderly men with high-risk nonmetastatic prostate cancer (HRnMPCa) do not receive radical treatment, despite the high mortality associated with conservative management. Objective: To investigate how age and comorbidity affect treatment of men with HRnMPCa. Design, setting, and participants: This was an observational nationwide register study during 2001-2012. We identified 19 190 men of <80 yr of age diagnosed with HRnMPCa in the National Prostate Cancer Register of Sweden and 95 948 age-matched men without prostate cancer in the register of the total population. Outcome measurements and statistical analysis: The outcome was the proportion of men with HRnMPCa receiving radical treatment (radical prostatectomy or radiotherapy). Vital status and the Charlson comorbidity index (CCI) were obtained from nationwide registers. The 10-yr survival of men without prostate cancer, stratified by age and CCI, was used as a measure of the life expectancy of the men with prostate cancer. Results and limitations: The proportions receiving radical treatment varied with life expectancy among men younger than 70 yr, whereas use of these treatments did not match the long life expectancy of men in their seventies with CCI 0-1. Only 10% of men aged 75-80 yr with CCI 0 received radical treatment despite 52% probability of 10-yr life expectancy, compared with approximately half of the men younger than 70 yr with a similar life expectancy. The use of radical treatment for HRnMPCa increased with time in all Swedish counties, but a threefold difference between counties remained in 2009-2012 for patients aged 70-80 yr with CCI 0-1. Uncertain external validity is a study limitation, and the impact of physician versus patient preferences on treatment selection could not be assessed. Conclusions: Otherwise healthy men in their seventies with HRnMPCa were less likely to receive radical treatment than younger men with a similar life expectancy, although increasing use of radical treatment was observed during the study period. Our findings highlight the need for improved methods for clinical decision-making, including improved assessment of life expectancy. Patient summary: We performed a nationwide register study that showed that many healthy men in their seventies live for at least another 10 yr. Despite this long life expectancy, men in their seventies with high-risk nonmetastatic prostate cancer were often not treated with radical prostatectomy or radiotherapy, possibly because their life expectancy was underestimated. Our study highlights the need for improved clinical decision-making, which should incorporate an assessment of the patient's life expectancy.
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| 5. |
- Bratt, Ola, et al.
(författare)
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Upper limit of cancer extent on biopsy defining very low-risk prostate cancer
- 2015
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 116:2, s. 213-219
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate how much Gleason pattern 3 cancer prostate biopsy specimens may contain without an increased risk of undetected more aggressive cancer, compared with the risk for cancers fulfilling the National Comprehensive Cancer Network (NCCN) criteria for very low-risk prostate cancer. Patients and Methods We identified 1286 men aged <70 years in the National Prostate Cancer Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c or T2 prostate cancer with Gleason pattern <= 3 only, prostate-specific antigen (PSA) level of <10 ng/mL and a PSA density of <0.15 ng/mL/mL. The association between the extent of cancer in the biopsies (the number and proportion of positive cores and the total cancer length in the cores in millimetres) and the likelihood of Gleason pattern 4-5 in the RP specimen was analysed with logistic regression. Results In all, 438 (34%) of the 1286 men had Gleason pattern 4-5 in the RP specimen. Increasing number and proportion of positive biopsy cores, as well as increasing biopsy cancer length were both significantly associated with increased risk of upgrading at RP in univariable analysis, but in multivariable analysis only biopsy cancer length remained significant. The 684 men with stage T1c and < 8 mm cancer had similar risk of upgrading regardless of whether the number of positive biopsy cores was 1-2 or 3-4 (28% vs 27% risk); upgrading was more common among the remaining men (40%, P < 0.01). Conclusions Men aged < 70 years with stage T1c prostate cancer and 3-4 biopsy cores with Gleason pattern 3 are not more likely to have undetected Gleason pattern 4-5 cancer than men with 1-2 cores with cancer, provided that the total biopsy cancer length is < 8 mm. We propose that the definition of very low-risk prostate cancer is widened accordingly.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Licciardello, Marco P., et al.
(författare)
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A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor
- 2017
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 13:7, s. 771-778
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Tidskriftsartikel (refereegranskat)abstract
- Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these drugs modulates the stability of the androgen receptor (AR) and resensitizes AR-mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for gamma-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients.
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| 9. |
- Loeb, Stacy, et al.
(författare)
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Defining Intermediate Risk Prostate Cancer Suitable for Active Surveillance
- 2019
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 201:2, s. 292-299
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Active surveillance of intermediate risk prostate cancer is controversial. Many active surveillance programs are limited to men with Grade Group 1 (Gleason 6) disease and prostate specific antigen less than 10 ng/ml. However, recent guidelines state that active surveillance can be considered in cases of limited Grade Group 2 (Gleason 3 thorn 4) despite limited data on outcomes. We compared prostatectomy outcomes between prostate cancer subgroups of intermediate risk vs low risk.Materials and Methods: We performed an observational study in the National Prostate Cancer Register of Sweden, which includes 98% of prostate cancer cases nationwide. From 2009 to 2012 radical prostatectomy was performed in 5,087 men with low risk prostate cancer (Grade Group 1, prostate specific antigen less than 10 ng/ml and cT2 or less) and intermediate risk prostate cancer (Grade Group 2, prostate specific antigen 10 to 20 ng/ml or T2). We compared upgrading and up staging between the groups based on the CAPRA (Cancer of the Prostate Risk Assessment) scores and published active surveillance criteria. Results were validated in an independent data set of cases diagnosed from 2013 to 2016.Results: Men with Grade Group 1, prostate specific antigen 10 to 15 ng/ml and prostate specific antigen density less than 0.15 ng/ml/cm3 did not significantly differ in upgrading or adverse pathology findings compared to men with low risk prostate cancer. Prostate specific antigen greater than 15 ng/ml or Grade Group 2 was associated with a significantly greater risk of aggressive prostate cancer. Men with low risk CAPRA scores (0 to 2) and Grade Group 2 disease were at almost threefold increased risk of upgrading and twofold increased risk of adverse pathology compared to men with low risk CAPRA, Grade Group 1 disease.Conclusions: Expanding the prostate specific antigen threshold to 15 ng/ml for Grade Group 1 prostate cancer would allow more men to elect active surveillance. This is unlikely to compromise outcomes, particularly if prostate specific antigen density is low. In contrast, caution should be exercised in offering active surveillance to men with prostate specific antigen greater than 15 ng/ml or Grade Group 2 prostate cancer.
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| 10. |
- Loeb, Stacy, et al.
(författare)
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Evaluation of the 2015 Gleason Grade Groups in a Nationwide Population-based Cohort
- 2016
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 69:6, s. 1135-1141
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Tidskriftsartikel (refereegranskat)abstract
- Background: New five-tiered Gleason grade groups (GGGs) were recently proposed, in which Gleason 6 is GGG 1, Gleason 3 + 4 is GGG 2, Gleason 4 + 3 is GGG 3, Gleason 8 is GGG 4, and Gleason 9-10 is GGG 5. Objective: To examine the performance of the new GGGs in men with prostate cancer from a nationwide population-based cohort. Design, setting, and participants: From the National Prostate Cancer Register of Sweden, we identified 5880 men diagnosed with prostate cancer from 2005 to 2007, including 4325 who had radical prostatectomy and 1555 treated with radiation therapy. Outcome measurements and statistical analysis: Kaplan-Meier survival analysis, Cox proportional hazards models, and concordance indices were used to examine the relationship between the GGGs and biochemical recurrence after radical prostatectomy and radiation therapy. Results and limitations: Among men treated with surgery, the 4-yr biochemical recurrence-free survival rates were 89%, 82%, 74%, 77%, and 49% for GGG 1-5 on biopsy, and 92%, 85%, 73%, 63%, and 51% based on prostatectomy GGG, respectively. For men treated by radiation therapy, men with biopsy GGG of 1-5 had 4-yr biochemical recurrence-free survival rates of 95%, 91%, 85%, 78%, and 70%. Adjusting for preoperative serum prostate-specific antigen and clinical stage, biopsy GGGs were significant independent predictors of biochemical recurrence after radical prostatectomy and radiation therapy. The new 5-tier system resulted in virtually no change in predictive accuracy compared with the current 3- and 4-tier classifications. Limitations include a median follow-up of 4.6 yr, precluding the ability to examine long-term oncologic outcomes. Conclusions: The newly proposed GGGs offer a simplified, user-friendly nomenclature to aid in patient counseling, with similar predictive accuracy in a population-based setting to previous classifications. Patient summary: The new Gleason grade groups, ranging from 1-5, provide a simplified, user-friendly classification system to predict the risk of recurrence after prostatectomy and radiation therapy.
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| 11. |
- Loeb, Stacy, et al.
(författare)
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Five-year Nationwide Follow-up Study of Active Surveillance for Prostate Cancer
- 2015
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 67:2, s. 233-238
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Tidskriftsartikel (refereegranskat)abstract
- Background: Active surveillance (AS) is an important yet underutilized strategy to reduce prostate cancer (PCa) overtreatment. Objective: To examine the 5-yr outcomes of AS in a population-based setting. Design, setting, and participants: From the National Prostate Cancer Register of Sweden, we identified 11 726 men <= 70 yr diagnosed with very low-risk to intermediate-risk PCa from 2003 to 2007 who completed 5 yr of follow-up. Of these men, 1729 (15%) chose AS for the primary management strategy. Outcome measurements and statistical analysis: We calculated the probability of discontinuation of AS over time, and Cox proportional hazards models were used to determine factors associated with discontinuation. Reasons for discontinuation were assessed by data extraction from medical charts. Results and limitations: By 5 yr, 64% of the men remained on AS. Predictors of discontinuation were younger age, fewer comorbidities, more education, higher prostate-specific antigen (PSA), and clinical stage T2 disease; marital status did not predict discontinuation. In a subset with data on the reason for discontinuation (86%), 20% of men discontinued because of patient preference, 52% because of PSA progression, 24% because of biopsy progression, and 3% for other reasons. Conclusions: In a population-based setting, the majority of men remained on AS at 5 yr. However, one-fifth of the men who discontinued AS did so for nonbiologic reasons. Thus, there is a need for support and counseling for men to continue AS in the absence of signs of progression to improve adherence to AS and decrease overtreatment. Patient summary: Active surveillance (AS) is an important option to delay or avoid treatment for men with favorable prostate cancer features. This study shows that at 5 yr, 64% of men across an entire population remained on AS. We concluded that AS is a durable option and that counseling may be useful to promote adherence for men without progression.
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| 12. |
- Loeb, Stacy, et al.
(författare)
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Immediate versus delayed prostatectomy : Nationwide population-based study
- 2016
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Ingår i: Scandinavian journal of urology. - : Informa UK Limited. - 2168-1805 .- 2168-1813. ; 50:4, s. 246-254
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to compare the outcome of immediate versus delayed radical prostatectomy (RP) in men with low-grade prostate cancer. Materials and methods: The study included a nationwide population-based cohort in the National Prostate Cancer Register of Sweden, of 7608 men with clinically localized, biopsy Gleason score 6 prostate cancer who underwent immediate or delayed RP in 1997-2007. Multivariable models compared RP pathology, use of salvage radiotherapy and prostate cancer mortality based on timing of RP (< 1, 1-2 or > 2 years after diagnosis). Median follow-up was 8.1 years. Results: Men undergoing RP more than 2 years after diagnosis had a higher risk of Gleason upgrading [odds ratio 2.93, 95% confidence interval (CI) 2.34-3.68] and an increased risk of salvage radiotherapy [hazard ratio (HR) 1.90, 95% CI 1.41-2.55], but no significant increase in prostate cancer-specific mortality (HR 1.85, 95% CI 0.57-5.99). In competing risk analysis, 7 year prostate cancer-specific cumulative mortality was similar, at less than 1%, for immediate RP and active surveillance regardless of later intervention. Limitations of this study include the lack of data on follow-up biopsies and the limited follow-up time. Conclusion: Men undergoing RP more than 2 years after diagnosis had more adverse pathological features and second line therapy, highlighting the trade-off in deferring immediate curative therapy. However, men with delayed RP constitute a minority with higher risk cancer among the much larger group of low-risk men initially surveilled, and the overall risk of prostate cancer mortality at 7 years was similarly low with immediate RP or active surveillance.
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| 13. |
- Loeb, Stacy, et al.
(författare)
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Meta-Analysis of the Association Between Phosphodiesterase Inhibitors (PDE5Is) and Risk of Melanoma
- 2017
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 109:8
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Tidskriftsartikel (refereegranskat)abstract
- The US Food and Drug Administration recently announced the need to evaluate the association between PDE5is and melanoma. We performed a meta-analysis on the association between PDE5i and melanoma using random effects models and examined whether it met Hill's criteria for causality. A systematic search of Medline, EMBASE, and the Cochrane Library from 1998 to 2016 identified three case-control studies and two cohort studies, including a total of 866 049 men, of whom 41 874 were diagnosed with melanoma. We found a summary estimate indicating an increased risk of melanoma in PDE5i users (relative risk = 1.12, 95% confidence interval = 1.02 to 1.23). However, there was no difference in risk between men with low and high exposure to PDE5i, and risk was higher for in situ melanoma than localized and high-risk melanoma, suggesting a lack of dose response and biological gradient. PDE5i use was also associated with basal cell cancer, suggesting a lack of specificity and likely confounding by ultraviolet exposure. Thus, although this meta-analysis found a statistically significant association between PDE5i and melanoma, it did not satisfy Hill's criteria for causality.
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| 14. |
- Loeb, Stacy, et al.
(författare)
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Phosphodiesterase Type 5 Inhibitor Use and Disease Recurrence After Prostate Cancer Treatment
- 2016
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 70:5, s. 824-828
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Phosphodiesterase type 5 inhibitor (PDE5i) use is common for management of erectile dysfunction. Single-institution studies have reported conflicting data on the relationship between PDE5i use and biochemical recurrence of prostate cancer (BCR) after radical prostatectomy.OBJECTIVE: To evaluate the association between PDE5i use and BCR after radical prostatectomy and radiation therapy in a nationwide population-based cohort.DESIGN, SETTING, AND PARTICIPANTS: This was a nested case-control study using the National Prostate Cancer Register of Sweden linked to the Prescribed Drug Register. Among men with localized prostate cancer who underwent primary radical prostatectomy or radiation therapy during 2006-2007 with 5 yr of follow-up, 293 had BCR after treatment (cases). For each case we identified 20 BCR-free controls (n=5767) using incidence density sampling.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable conditional logistic regression was used to examine the association between PDE5i use and BCR risk. Separate multivariable models including clinical variables for men undergoing prostatectomy or radiotherapy and including surgical pathology after prostatectomy were also analyzed.RESULTS AND LIMITATIONS: PDE5i use was not associated with BCR after radical prostatectomy (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.59-1.03) or radiation therapy (OR 0.98, 95% CI 0.49-1.97) after adjusting for marital status, education, income, prostate-specific antigen, clinical stage, Gleason score, and proportion of positive biopsies. Results were similar after additional adjustment for surgical pathology (OR 0.86, 95% CI 0.64-1.16). Men whose cumulative number of PDE5i pills was above the median had a slightly lower BCR risk after prostatectomy in the clinical model, and no difference in BCR risk after adjustment for pathologic tumor features.CONCLUSIONS: Our results from a population-based cohort suggest that BCR risk is not higher among men using PDE5i after prostate cancer treatment.PATIENT SUMMARY: Erectile dysfunction medications are not associated with a higher risk of disease recurrence after prostate cancer treatment.
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| 15. |
- Loeb, Stacy, et al.
(författare)
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Phosphodiesterase type 5 inhibitors (PDE5i) and prostate cancer recurrence
- 2016
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Ingår i: Journal of Clinical Oncology. - NYU, Langone Med Ctr, New York, NY USA. Univ Uppsala Hosp, Uppsala, Sweden. Umea Univ Hosp, S-90185 Umea, Sweden. Prostate Canc Ctr Hamburg Eppendorf, Martini Clin, Hamburg, Germany. Kings Coll London, Sch Med, Div Canc Studies, Canc Epidemiol Grp, London WC2R 2LS, England. Umea Univ, Umea, Sweden.. - 0732-183X .- 1527-7755. ; 34:2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 16. |
- Loeb, Stacy, et al.
(författare)
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Testosterone Replacement Therapy and Risk of Favorable and Aggressive Prostate Cancer
- 2017
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Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 35:13, s. 1430-1436
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The association between exposure to testosterone replacement therapy (TRT) and prostate cancer risk is controversial. The objective was to examine this association through nationwide, population-based registry data. Methods We performed a nested case-control study in the National Prostate Cancer Register of Sweden, which includes all 38,570 prostate cancer cases diagnosed from 2009 to 2012, and 192,838 age-matched men free of prostate cancer. Multivariable conditional logistic regression was used to examine associations between TRT and risk of prostate cancer (overall, favorable, and aggressive). Results Two hundred eighty-four patients with prostate cancer (1%) and 1,378 control cases (1%) filled prescriptions for TRT. In multivariable analysis, no association was found between TRT and overall prostate cancer risk (odds ratio [OR], 1.03; 95% CI, 0.90 to 1.17). However, patients who received TRT hadmore favorable-risk prostate cancer (OR, 1.35; 95% CI, 1.16 to 1.56) and a lower risk of aggressive prostate cancer (OR, 0.50; 95% CI, 0.37 to 0.67). The increase in favorable-risk prostate cancer was already observed within the first year of TRT (OR, 1.61; 95% CI, 1.10 to 2.34), whereas the lower risk of aggressive disease was observed after > 1 year of TRT (OR, 0.44; 95% CI, 0.32 to 0.61). After adjusting for previous biopsy findings as an indicator of diagnostic activity, TRT remained significantly associated with more favorable-risk prostate cancer and lower risk of aggressive prostate cancer. Conclusion The early increase in favorable-risk prostate cancer among patients who received TRT suggests a detection bias, whereas the decrease in risk of aggressive prostate cancer is a novel finding that warrants further investigation. (C) 2017 by American Society of Clinical Oncology.
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| 17. |
- Loeb, Stacy, et al.
(författare)
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Uptake of active surveillance for very-low-risk prostate cancer in Sweden
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:10, s. 1393-1398
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Active surveillance is an important option to reduce prostate cancer overtreatment, but it remains underutilized in many countries. Models from the United States show that greater use of active surveillance is important for prostate cancer screening to be cost-effective.oObjectives: To perform an up-to-date, nationwide, population-based study on use of active surveillance for localized prostate cancer in Sweden.Design, setting, and participants: Cross-sectional study in the National Prostate Cancer Register (NPCR) of Sweden from 2009 through 2014. The NPCR has data on 98% of prostate cancers diagnosed in Sweden and has comprehensive linkages to other nationwide databases. Overall, 32 518 men with a median age of 67 years were diagnosed with favorable-risk prostate cancer, including 4693, 15 403, and 17 115 men with very-low-risk (subset of the low-risk group) (clinical stage, T1c; Gleason score, ≤6; prostate-specific antigen [PSA], <10 ng/mL; PSA density <0.15 ng/mL/cm3; and <8-mm total cancer length in ≤4 positive biopsy cores), low-risk (including all men in the very-low-risk group) (T1-T2; Gleason score, ≤6; and PSA, <10 ng/mL), and intermediate-risk disease (T1-T2 with Gleason score, 7 and/or PSA, 10-20 ng/mL).Exposures: Diagnosis with favorable-risk prostate cancer.Main outcomes and measures: Utilization of active surveillance.Results: The use of active surveillance increased in men of all ages from 57% (380 of 665) to 91% (939 of 1027) for very-low-risk prostate cancer and from 40% (1159 of 2895) to 74% (1951 of 2644) for low-risk prostate cancer, with the strongest increase occurring from 2011 onward. Among men aged 50 to 59 years, 88% (211 of 240) with very-low-risk and 68% (351 of 518) with low-risk disease chose active surveillance in 2014. Use of active surveillance for intermediate-risk disease remained lower, 19% (561 of 3030) in 2014.Conclusions and relevance: Active surveillance has become the dominant management for low-risk prostate cancer among men in Sweden, with the highest rates yet reported and almost complete uptake for very-low-risk cancer. These data should serve as a benchmark to compare the use of active surveillance for favorable-risk disease around the world.
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| 18. |
- 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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| 19. |
- Lundström, Karl-Johan, et al.
(författare)
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Small bowel obstruction and abdominal pain after robotic versus open radical prostatectomy
- 2016
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Ingår i: Scandinavian journal of urology. - : Informa UK Limited. - 2168-1805 .- 2168-1813. ; 50:3, s. 155-159
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to examine whether intraperitoneal robot-assisted surgery leads to small bowel obstruction (SBO), possibly caused by the formation of intra-abdominal adhesions.Materials and methods: In total, 7256 men treated by intraperitoneal robot-assisted radical prostatectomy (RARP) and 9787 men treated by retropubic radical prostatectomy (RRP) in 2005-2012 were identified in the Prostate Cancer data Base Sweden (PCBaSe). Multivariable Cox proportional hazards models were used to calculate the risk of readmission for SBO, SBO-related surgery and admissions due to abdominal pain up to 5 years postoperatively.Results: During the first postoperative year, the risk of readmission for SBO was higher after RARP than after RRP [hazard ratio (HR) 1.92, 95% confidence interval (CI) 1.14-3.25] but after 5 years there was no significant difference (HR 1.28, 95% CI 0.86-1.91), and there was no difference in the risk of SBO surgery during any period. The risk of admission for abdominal pain was significantly increased after RARP during the first year (HR 2.24, 95% CI 1.50-3.33) but not after 5 years (HR 1.23, 95% CI 0.92-1.63).Conclusion: Intraperitoneal RARP had an increased risk of SBO and abdominal pain in the short term during the first year, but not in the long term, compared to RRP.
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| 20. |
- Nugin, Hampus, et al.
(författare)
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Work-up and treatment of prostate cancer before and after publication of the first national guidelines on prostate cancer care in Sweden
- 2018
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Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 52:4, s. 277-284
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: In 2007, the Swedish National Board of Health and Welfare published the first Swedish guidelines on prostate cancer (PCa) to improve care and decrease geographical and social inequalities. The aim of this analysis was to assess how these guidelines affected PCa care.Materials and Methods: Work-up and treatment for men diagnosed with PCa between 1998 and 2014 were assessed by use of data in the Prostate Cancer data Base Sweden (PCBaSe) with information from the National Prostate Cancer Register (NPCR) and other healthcare registries and demographic databases.Results: Overall, there were modest improvements in the performance for 14 selected quality indicators, with some notable exceptions. There was a strong increase in the use of active surveillance for very low-risk PCa, up from 56% in 2009 to 92% in 2014, and use of bone imaging for high-risk PCa up from 50% in 2008 to 77% in 2014. There were large differences in work-up and treatment of PCa between healthcare providers with modest decreases over time. The differences between counties were larger than differences according to socioeconomic status with one exception: use of curative treatment for high-risk PCa was more common in men with high income, highest versus lowest tertile, OR 2.74 (95% CI, 1.85-4.06).Conclusion: The modest improvements in PCa care after the publications of national guidelines indicate that if these are to make an impact on care, feedback to each point of care on their performance as well as local quality improvement programs implementing the guidelines are needed.
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| 21. |
- Plym, Anna, et al.
(författare)
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Drug Prescription for Erectile Dysfunction Before and After Diagnosis of Localized Prostate Cancer
- 2014
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Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 11:8, s. 2100-2108
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Despite the high prevalence of erectile dysfunction (ED) in men with prostate cancer, little is known about the use of ED drugs. Also, the possible influence of socioeconomic factors on ED drug use has not been studied previously.Aim: The aim of this study was to examine determinants and patterns of ED drug use before and after diagnosis in men with localized prostate cancer.Methods: Using a nationwide population‐based cohort, 25,390 men with localized prostate cancer diagnosed between 2006 and 2009 and 126,944 control men were identified and followed for filled ED drug prescriptions over a 3‐year period, ranging from 1 year before and up to 2 years after diagnosis.Main Outcome Measures: The main outcome measure was the proportion of men with at least one filled ED drug prescription after diagnosis.Results: The number of men using ED drugs increased markedly following diagnosis. Men who underwent radical prostatectomy had the strongest increase, with a cumulative proportion of 74% for at least one filled prescription within the first 2 years after diagnosis. The corresponding proportion was 33% in men treated with radiotherapy, 21% in men on active surveillance, 10% in men on watchful waiting, and 8% in control men. Among men who underwent prostatectomy, usage attenuated over time. Determinants of postdiagnostic use were young age at diagnosis, high income, high education, and a low‐ or intermediate‐risk cancer.Conclusion: Although drugs for ED are commonly prescribed after diagnosis, use among most men is transient and influenced by socioeconomic status. Posttreatment counseling and affordable ED drugs are likely to reduce treatment dropout and disparities in use and help improve sexual health and quality of life in men with prostate cancer.
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| 22. |
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| 23. |
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| 24. |
- 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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| 25. |
- Thomsen, Frederik B., et al.
(författare)
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Risk of malignant melanoma in men with prostate cancer : Nationwide, population-based cohort study
- 2016
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 138:9, s. 2154-2160
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Tidskriftsartikel (refereegranskat)abstract
- An increased risk of malignant melanoma has been observed in men with prostate cancer. To assess potential shared risk factors and confounding factors, we analysed risk of melanoma in men with prostate cancer including information on tumor characteristics and demographics including socioeconomic status. In The Prostate Cancer data Base Sweden, risk of melanoma was assessed in a cohort of men with prostate cancer and in a comparison cohort of prostate-cancer free men. Data on prostate cancer risk category, melanoma stage, basal cell carcinoma, location of residency, and socioeconomic status were obtained from nationwide registers. Melanoma was diagnosed in 830/108,145 (0.78%) men with prostate cancer and in 3,699/556,792 (0.66%) prostate cancer-free men. In multivariable Cox regression models, men with prostate cancer had a significantly increased risk of melanoma (HR 1.18, 95% CI 1.09-1.27), and so had married men, men with high education and income, and men residing in southern Sweden. The strongest associations were observed for stage 0 melanoma in men with low-risk prostate cancer (HR 1.45, 1.14-1.86), high education (HR 1.87, 1.60-2.18) and top income (HR 1.61, 1.34-1.93), respectively, whereas there was no association between these factors and late-stage melanoma. Men with prostate cancer also had an increased risk of basal cell carcinoma (HR 1.18, 1.15-1.22). In conclusion, men with low-risk prostate cancer, high education, high income and residency in southern Sweden had an increased risk of early-stage melanoma. What's new? Men with a history of prostate cancer are at increased risk of melanoma, an association suspected of arising from a common mechanism of androgen exposure. Other factors, however, including tumor characteristics and socioeconomic factors, may also play a role. In this population-based study in Sweden, among men with prostate cancer, melanoma risk was found to be greatest for low-risk prostate tumors. The association was exclusive to early-stage melanoma. Risk of basal cell carcinoma was also elevated among men with prostate cancer. The findings throw new light on potential shared risk factors between prostate cancer and skin malignancies.
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