| 1. |
- Bratt, Ola, et al.
(author)
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Undertreatment of Men in Their Seventies with High-risk Nonmetastatic Prostate Cancer
- 2015
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 68:1, s. 53-58
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Journal article (peer-reviewed)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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| 2. |
- Bratt, Ola, et al.
(author)
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Upper limit of cancer extent on biopsy defining very low-risk prostate cancer
- 2015
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In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 116:2, s. 213-219
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Journal article (peer-reviewed)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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| 3. |
- Loeb, Stacy, et al.
(author)
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Use of Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction and Risk of Malignant Melanoma
- 2015
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 313:24, s. 2449-2455
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Journal article (peer-reviewed)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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| 4. |
- Thomsen, Frederik B., et al.
(author)
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Risk of malignant melanoma in men with prostate cancer : Nationwide, population-based cohort study
- 2016
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 138:9, s. 2154-2160
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Journal article (peer-reviewed)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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| 5. |
- Björklund, Johan, et al.
(author)
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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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In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 118:2, s. 302-306
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Journal article (peer-reviewed)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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| 6. |
- Fridriksson, Jon Örn, et al.
(author)
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Long-term adverse effects after retropubic and robot-assisted radical prostatectomy : Nationwide, population-based study
- 2017
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In: Journal of Surgical Oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 116:4, s. 500-506
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Journal article (peer-reviewed)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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| 7. |
- Loeb, Stacy, et al.
(author)
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Evaluation of the 2015 Gleason Grade Groups in a Nationwide Population-based Cohort
- 2016
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 69:6, s. 1135-1141
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Journal article (peer-reviewed)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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| 8. |
- Plym, Anna, et al.
(author)
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Drug Prescription for Erectile Dysfunction Before and After Diagnosis of Localized Prostate Cancer
- 2014
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In: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 11:8, s. 2100-2108
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Journal article (peer-reviewed)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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| 9. |
- Thomsen, Frederik B., et al.
(author)
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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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In: Journal of Surgical Oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 114:6, s. 664-670
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Journal article (peer-reviewed)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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| 10. |
- Van Hemelrijck, Mieke, et al.
(author)
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Causes of death in men with localized prostate cancer : a nationwide, population-based study
- 2016
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In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 117:3, s. 507-514
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Journal article (peer-reviewed)abstract
- Objective To detail the distribution of causes of death from localized prostate cancer (PCa). Patients and Methods The database PCBase Sweden links the Swedish National Prostate Cancer Register with other nationwide population-based healthcare registers. We selected all 57 187 men diagnosed with localized PCa between 1997 and 2009 and their 114 374 PCa-free control subjects, matched according to age and county of residence. Mortality was calculated using competing risk regression analyses, taking into account PCa risk category, age and Charlson comorbidity index (CCI). Results In men with low-risk PCa, all-cause mortality was lower compared with that in corresponding PCa-free men: 10-year all-cause mortality was 18% for men diagnosed at age 70 years, with a CCI score of 0, and 21% among corresponding control subjects. Of these cases, 31% died from cardiovascular disease (CVD) compared with 37% of the corresponding control subjects. For men with low-risk PCa, 10-year PCa-mortality was 0.4, 1 and 3% when diagnosed at age 50, 60 and 70 years, respectively. PCa was the third most common cause of death (18%), after CVD (31%) and other cancers (30%). By contrast, PCa was the most common cause of death in men with intermediate-and high-risk localized PCa. Conclusions Men with low-risk PCa had lower all-cause mortality than PCa-free men because of lower CVD mortality, driven by early detection selection; however, for men with intermediateor high-risk disease, the rate of PCa death was substantial, irrespective of CCI score, and this was even more pronounced for those diagnosed at age 50 or 60 years.
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