| 1. |
- Thor, Anna, et al.
(författare)
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Primary retroperitoneal lymph node dissection as treatment for low-volume metastatic seminoma in a population-based cohort : the Swedish Norwegian testicular cancer group experience
- 2024
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 65, s. 13-19
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: There is an unmet need to avoid long-term morbidity associated with standard cytotoxic treatment for low-volume metastatic seminoma. Our aim was to assess the oncological efficacy and surgical safety of retroperitoneal lymph node dissection (RPLND) as treatment in a population-based cohort of metastatic seminoma patients with limited retroperitoneal lymphadenopathy.Methods: Sixty-two seminoma patients in Norway and Sweden were included in the cohort from 2019 to 2022. Patients with lymphadenopathy ≤3 cm, having primary clinical stage (CS) IIA/B or CS I with a relapse, were operated with uni- or bilateral template RPLND, open or robot assisted. The outcome measures included surgical complications as per Clavien-Dindo, and Kaplan-Meier survival estimates for 24-mo progression-free survival (PFS) and overall survival (OS).Key findings and limitations: In the cohort, 33 (53%) had CS I with a relapse during surveillance, six (10%) CS I with a relapse following adjuvant chemotherapy, and 23 (37%) initial CS IIA/B. Metastatic seminoma was verified in 58 patients (94%) with a median largest diameter of 18 mm (interquartile range [IQR] 13–24). Robot-assisted RPLND was performed in 40 patients (65%). Clavien-Dindo III complications were observed in three patients (5%); no grade ≥IV complications occurred. Eighteen patients (29%) received adjuvant chemotherapy after surgery. The median follow-up was 23 mo (IQR 16–30), and recurrence occurred in six patients (10%) after a median of 8 mo (IQR 4–14). PFS was 90% (95% confidence interval: 0.86–1) and OS was 100% at 24 mo.Conclusions and clinical implications: RPLND as primary treatment is an option for selected low-stage seminomas with a limited burden of disease, showing low complications and low relapse rates, with the potential to reduce long-term morbidity.Patient summary: In seminoma patients with limited metastatic spread, surgery is a treatment option offering an alternative to chemotherapy or radiation. This paper covers the first 62 patients operated in Norway and Sweden.
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| 2. |
- Grotta, Alessandra, et al.
(författare)
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Physical activity and body mass index as predictors of prostate cancer risk
- 2015
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Ingår i: World journal of urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 33:10, s. 1495-1502
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Physical activity and body mass index (BMI) are involved in prostate cancer etiology; possible biologic mechanisms include their effects on hormonal levels. Our aim was to investigate the relationship between physical activity, obesity, and prostate cancer.METHODS: We followed a cohort of 13,109 Swedish men for 13 years and investigated the association of self-reported physical activity and BMI at baseline with prostate cancer incidence. We further analyzed whether BMI could modulate effects of physical activity. Occupational, recreational, and total physical activity were analyzed in relation to overall, localized, and advanced prostate cancer.RESULTS: During the study follow-up, we observed a total of 904 cases of prostate cancer (429 localized, 407 advanced, and 68 unclassified). High levels of occupational physical activity were associated with a nonsignificantly decreased risk of overall (HR 0.81, 95 % CI 0.61-1.07), localized (HR 0.75, 95 % CI 0.51-1.12), and advanced (HR 0.85, 95 % CI 0.55-1.31) prostate cancer. We found no association between high BMI and risk of prostate cancer incidence: We observed, however, a significant interaction between BMI and leisure physical activity.CONCLUSION: No association was confirmed between total physical activity and localized or advanced prostate cancer. The highest, relative to the lowest, level of occupational physical activity tended to be linked to a lower risk of prostate cancer, with a suggested dose-response relationship. We found no association between high BMI and risk of prostate cancer incidence; however, our analyses suggested an interaction between BMI and physical activity during recreational time that merits further investigation in future studies.
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| 3. |
- Akre [Fall], Katja, 1971-, et al.
(författare)
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Risk for gastric cancer after antibiotic prophylaxis in patients undergoing hip replacement
- 2000
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Ingår i: Cancer Research. - Birmingham, USA : American Asoociation for Cancer Research. - 0008-5472 .- 1538-7445. ; 60, s. 6376-
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Tidskriftsartikel (refereegranskat)abstract
- Despite strong evidence of an association between Helicobacter pylori and gastric cancer, the benefit of eradicating H. pylori infection is unknown. Our aim was to test the hypothesis that exposure to high doses of antibiotics reduces risk for gastric cancer via possible eradication of H. pylori We conducted a nationwide case-control study nested in a cohort of 39,154 patients who underwent hip replacement surgery between 1965 and 1983. Such patients frequently receive prophylactic antibiotic treatment. During follow-up through 1989, we identified 189 incident cases of gastric cancer. For each case, three controls were selected from the cohort. Exposure data were abstracted from hospital records. Blood samples from a separate cohort undergoing hip replacement surgery were analyzed for anti-H. pylori IgG before and after surgery. Both long-term antibiotic treatment before surgery [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.7] and prophylactic antibiotic treatment (OR, 0.7; 95% CI, 0.5-1.1) conferred a reduction in gastric cancer risk. The reduction appeared stronger after 5 years (OR, 0.6; 95% CI, 0.3-1.2) than during shorter follow-up after hip replacement (OR, 0.8; 95% CI, 0.4-1.7). There was an apparent decrease in risk with increasing body weight-adjusted doses of antibiotics (P = 0.13). However, the rate of H. pylori antibody disappearance was not strikingly higher in the cohort of patients undergoing hip replacement than in a control cohort. Our findings provide indirect support for the hypothesis that treatment with antibiotics at a relatively advanced age reduces the risk of gastric cancer.
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| 4. |
- Akre, Olof, et al.
(författare)
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Epstein-Barr virus and cytomegalovirus in relation to testicular-cancer risk : a nested case-control study
- 1999
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Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 82:1, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- An infectious etiology of testicular cancer has been suggested. We have evaluated seroreactivity against cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to testicular-cancer risk in a case-control study, nested within a cohort of prospectively collected serum specimens from 293,692 individuals. For each of 81 cases of testicular cancer identified, 3 controls were randomly selected from the cohort. Serum IgG antibody titers against CMV and EBV were determined using enzyme-linked immunosorbent assays (ELISAs) and immunofluorescence methods. Odds ratios (OR) were obtained from conditional logistic-regression models. No association was found between CMV positivity and testicular cancer overall (OR = 1.08; 95% confidence interval 0.60-1.94); risk for testicular seminoma was increased among CMV seropositive [OR = 1.70 (0.80-3.59)], whereas seropositivity was associated with decreased risk for testicular non-seminoma [OR = 0.54 (0.19-1.56)] (p for heterogeneity, 0.09). For EBV, the risk for testicular cancer was increased among individuals seropositive for viral capsid antigen (VCA) [OR = 2.74 (0.62-12.12)]. The results lend some support to the hypothesis of an infectious etiology, and we propose that future studies should take into account age at infection.
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| 5. |
- Akre, Olof
(författare)
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Etiological insights into the testicular cancer epidemic
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to search for causes of the testicular cancer epidemic through epidemiologic studies of testicular cancer and possibly related conditions, such as urogenital birth defects and subfertility. First, we assessed changes in fertility over time by studying time-to-pregnancy among primiparous women in Sweden from 1983 through 1993 using data from the Medical Birth Registry. The analyses revealed a substantial decrease of subfertility over successive maternal birth cohorts. Thus, there was no detectable increment in subfertility problems paralleling the increase in testicular cancer during the study period. Second, we performed a nested case-control study to evaluate specific perinatal characteristics as risk factors for testicular cancer. Perinatal information about 232 case patients and 904 control subjects was obtained from birth records. We found elevated risks associated with neonatal jaundice and high or low birth weight. When the two histopathologic types of testicular cancer, seminoma and nonseminoma, were analyzed separately, high socioeconomic status, neonatal jaundice, and low birth weight were associated with nonseminomas, whereas high placental weight appeared to increase the risk for seminomas. Third, we investigated risk factor patterns for cryptorchidism and hypospadias in two case-control studies using record linkage between the Swedish Inpatient and Birth Registries. Cases were 2,782 and 1,220 boys operated for cryptorchidism or hypospadias, respectively. Partly similar risk patterns were revealed for the two conditions: both were positively associated with other congenital malformations and inversely with maternal parity. There was also evidence of a strong joint effect of intrauterine growth retardation and short duration of gestation, with highly increased risks among preterm boys born small-for-gestational-age. Fourth, seroreactivity against cytomegalovirus (CMV) and Epstein-Barr virus (EBV) was evaluated in relation to testicular cancer risk in a case-control study, nested in a cohort of prospectively collected serum specimens from 293,692 individuals. For 81 cases of testicular cancer and 242 controls, serum IgG titers were determined using enzyme-linked immunosorbent assays and immunofluorescence methods. No association was found between CMV positivity and testicular cancer. For EBV, the risk of testicular cancer was increased almost threefold among individuals seropositive for viral capsid antigen. Power limitations, however, hamper conclusive inference. Fifth, we conducted a cohort study using anthropometrical data of 477,248 men who attended a tuberculosis-screening program in Norway between 1963 and 1975. Five hundred and fifty three cases of testicular cancer were diagnosed up to 1989. High body mass index (BMI) was associated with a decreased risk of testicular cancer whereas height was positively associated with risk. The associations appeared more pronounced for seminomas than for nonseminomas. Thus, hormonal exposures may have different effects on different histologic subgroups, and if so, such exposures cannot explain the dramatic rise in testicular cancer incidence, which comprises both types. It is furthermore hypothesized that impaired placental function is important in the etiology of testicular cancer, and that improved survival of growth-retarded and prematurely born neonates may have contributed to the increasing trend.
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| 6. |
- Akre, Olof, et al.
(författare)
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Maternal and gestational risk factors for hypospadias
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:8, s. 1071-1076
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: An increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown. OBJECTIVES: Our goal was to assess the association between risk of hypospadias and indicators of placental function and endogenous hormone levels, exposure to exogenous hormones, maternal diet during pregnancy, and other environmental factors. METHODS: We conducted a case-control study in Sweden and Denmark from 2000 through 2005 using self-administered questionnaires completed by mothers of hypospadias cases and matched controls. The response rate was 88% and 81% among mothers of cases and controls, respectively. The analyses included 292 cases and 427 controls. RESULTS: A diet during pregnancy lacking both fish and meat was associated with a more than 4-fold increased risk of hypospadias [odds ratio (OR) 4.6, 95% confidence interval (CI), 1.6-13.3]. Boys born to obese [body mass index (BMI) > ;= 30] women had a more than 2-fold increased risk of hypospadias (OR = 2.6, 95% CI, 1.2-5.7) compared with boys born to mothers with a normal weight (BMI = 20-24). Maternal hypertension during pregnancy and absence of maternal nausea increased a boy's risk of hypospadias 2.0-fold (95% CI, 1.1-3.7) and 1.8-fold (95% CI, 1.2-2.8), respectively. Nausea in late pregnancy also appeared to be positively associated with hypospadias risk (OR = 7.6, 95% CI, 1.1-53). CONCLUSIONS: A pregnancy diet lacking meat and fish appears to increase the risk of hypospadias in the offspring. Other risk associations were compatible with a role for placental insufficiency in the etiology of hypospadias.
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| 7. |
- Akre, Olof, et al.
(författare)
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Mortality Among Men with Locally Advanced Prostate Cancer Managed with Noncurative Intent: A Nationwide Study in PCBaSe Sweden
- 2011
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 60:3, s. 554-563
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment. Objective: To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent. Design, setting, and participants: We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis. Measurements: We followed up the patient cohort in the Cause of Death Register for <= 11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics. Results and limitations: The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25-32%) for Gleason score (GS) 2-6, 41% (95% CI, 38-44%) for GS 7, 52% (95% CI, 47-57%) for GS 8, and 64% (95% CI, 59-69%) for GS 9-10. Even for men aged >85 yr at diagnosis with GS 8-10, PCa was a major cause of death: 42% (95% CI, 37-47%). Men with locally advanced disease and a PSA <4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status. Conclusions: The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 8. |
- 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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| 9. |
- Björklund, Johan, et al.
(författare)
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The 90-day cause-specific mortality after radical prostatectomy : a nationwide population-based study.
- 2022
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Ingår i: BJU International. - : John Wiley & Sons. - 1464-4096 .- 1464-410X. ; 129:3, s. 318-324
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the cause-specific mortality in the postoperative period after radical prostatectomy (RP) for prostate cancer (PCa).METHODS: In the National Prostate Cancer Register of Sweden (NPCR), we identified all men who died within 90 days after RP performed 1998-2018 and we assessed cause of death in a chart review. We compared the adjudications of death from our medical record review with those in in the Swedish Cause of Death Registry (CDR).RESULTS: Out of 44 635, 58 (0.13%) men who had undergone RP from 1998 through 2018 died within 90 days after RP. Per medical record review the most common causes of death were cardiac disease (30%) and venous thromboembolic events (VTE; 21%). No men died of metastatic PCa as was first indicated in the CDR. After robot-assisted RP (RARP) or open retropubic RP (RRP), the postoperative mortality was 0.09% (19/21 520) and 0.19% (37/19 635), respectively. The effect off modality was confounded mainly by year of surgery, age at surgery, Charlson Comorbidity Index score and the concomitant pelvic lymph node dissection.CONCLUSION: The validated absolute 90-day mortality after RP was 1.3/1000 during the 21-year study period. Cardiovascular diseases were the most common causes of death after RP. Our validation of the CDR refuted the occurrence of postoperative deaths from metastatic PCa. There were differences in rates and type of mortality between RRP and RARP, but the RARP cohort was more recent than the RRP cohort, which likely explain the differences.
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| 10. |
- Bratt, Ola, et al.
(författare)
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Family History and Probability of Prostate Cancer, Differentiated by Risk Category : A Nationwide Population-Based Study
- 2016
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 108:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Familial prostate cancer risk estimates are inflated by clinically insignificant low-risk cancer, diagnosed after prostate-specific antigen testing. We provide age-specific probabilities of non-low-and high-risk prostate cancer. Methods: Fifty-one thousand, eight hundred ninety-seven brothers of 32 807 men with prostate cancer were identified in Prostate Cancer data Base Sweden (PCBaSe). Nelson-Aalen estimates with 95% confidence intervals (CIs) were calculated for cumulative, family history-stratified probabilities of any, non-low-(any of Gleason score >= 7, prostate-specific antigen [PSA] >= 10 ng/mL, T3-4, N1, and/or M1) and high-risk prostate cancer (Gleason score >= 8 and/or T3-4 and/or PSA >= 20 ng/mL and/or N1 and/or M1). Results: The population probability of any prostate cancer was 4.8% (95% CI = 4.8% to 4.9%) at age 65 years and 12.9% (95% CI = 12.8% to 12.9%) at age 75 years, of non-low-risk prostate cancer 2.8% (95% CI = 2.7% to 2.8%) at age 65 years and 8.9% (95% CI = 8.8% to 8.9%) at age 75 years, and of high-risk prostate cancer 1.4% (95% CI = 1.3% to 1.4%) at age 65 years and 5.2% (95% CI = 5.1% to 5.2%) at age 75 years. For men with one affected brother, probabilities of any prostate cancer were 14.9% (95% CI = 14.1% to 15.8%) at age 65 years and 30.3% (95% CI = 29.3% to 31.3%) at age 75 years, of non-low-risk prostate cancer 7.3% (95% CI = 6.7% to 7.9%) at age 65 years and 18.8% (95% CI = 17.9% to 19.6%) at age 75 years, and of high-risk prostate cancer 3.0% (95% CI = 2.6% to 3.4%) at age 65 years and 8.9% (95% CI = 8.2% to 9.5%) at age 75 years. Probabilities were higher for men with a stronger family history. For example, men with two affected brothers had a 13.6% (95% CI = 9.9% to 17.6 %) probability of high-risk cancer at age 75 years. Conclusions: The age-specific probabilities of non-low-and high-risk cancer presented here are more informative than relative risks of any prostate cancer and more suitable to use for counseling men with a family history of prostate cancer.
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| 11. |
- Bratt, Ola, 1963, et al.
(författare)
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Population-based Organised Prostate Cancer Testing: Results from the First Invitation of 50-year-old Men
- 2024
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Ingår i: European Urology. - 0302-2838 .- 1873-7560. ; 85:3, s. 207-214
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Tidskriftsartikel (refereegranskat)abstract
- Background: The European Union recently recommended evaluation of the feasibility of organised prostate cancer screening. In Sweden, regional population-based organised prostate cancer testing (OPT) programmes were introduced in 2020. Objective: To describe initial participation rates and diagnostic outcomes. Design, setting, and participants: The three most populated Swedish regions invited all men aged 50 yr to OPT by a letter in 2020–2022. Men with prostate-specific antigen (PSA) ≥3 ng/ml were referred for prostate magnetic resonance imaging (MRI). PSA assays differed across regions. Men with Prostate Imaging Reporting and Data System (PI-RADS) 1–3 and PSA density ≥0.15 ng/ml/cm3 or PI-RADS 4–5 were referred for a biopsy. Data were obtained from the Swedish Register for Organised Prostate Cancer Testing. Outcome measurements and statistical analysis: Overall and regional participation rates, PSA distributions, PI-RADS score distributions, cancer detection, and treatment were evaluated. Results and limitations: A total of 23 855 (35%) of 68 060 invited men participated; 696 (2.9%) had PSA ≥3 ng/ml, and of them, 306 (44%) had a biopsy indication and 221 (32%) had a biopsy. On biopsy, 93 (42%) had Gleason grade group ≥2 (0.39% of PSA-tested men) and 44 (20%) Gleason grade group 1 cancer. Most men with cancer had treatment with curative intent (70%) or were under active surveillance (28%). Across regions, proportions of men with PSA ≥3 ng/ml ranged from 2.3% to 4.0%, and those with PI-RADS score 4–5 ranged from 12% to 21%. A limitation is that results are applicable only to first testing of men in their early 50s. Conclusions: The OPT programmes are feasible with good compliance to the diagnostic pathway. The use of MRI and PSA density avoided a biopsy for over half of the men with PSA ≥3 ng/ml. Inter-regional differences in diagnostic outcomes show a need for standardisation of the diagnostic pathway's components. Patient summary: We report the diagnostic outcomes of inviting 68 000 50-yr-old men to organised prostate cancer testing.
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| 12. |
- 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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| 13. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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Quantity and quality of nucleic acids extracted from archival formalin fixed paraffin embedded prostate biopsies
- 2018
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Ingår i: BMC Medical Research Methodology. - : BioMed Central. - 1471-2288. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Sweden, human tissue samples obtained from diagnostic and surgical procedures have for decades been routinely stored in a formalin-fixed, paraffin-embedded, form. Through linkage with nationwide registers, these samples are available for molecular studies to identify biomarkers predicting mortality even in slow-progressing prostate cancer. However, tissue fixation causes modifications of nucleic acids, making it challenging to extract high-quality nucleic acids from formalin fixated tissues.METHODS: In this study, the efficiency of five commercial nucleic acid extraction kits was compared on 30 prostate biopsies with normal histology, and the quantity and quality of the products were compared using spectrophotometry and Agilent's BioAnalyzer. Student's t-test's and Bland-Altman analyses were performed in order to investigate differences in nucleic acid quantity and quality between the five kits. The best performing extraction kits were subsequently tested on an additional 84 prostate tumor tissues. A Spearman's correlation test and linear regression analyses were performed in order to investigate the impact of tissue age and amount of tissue on nucleic acid quantity and quality.RESULTS: Nucleic acids extracted with RNeasy® FFPE and QIAamp® DNA FFPE Tissue kit had the highest quantity and quality, and was used for extraction from 84 tumor tissues. Nucleic acids were successfully extracted from all biopsies, and the amount of tumor (in millimeter) was found to have the strongest association with quantity and quality of nucleic acids.CONCLUSIONS: To conclude, this study shows that the choice of nucleic acid extraction kit affects the quantity and quality of extracted products. Furthermore, we show that extraction of nucleic acids from archival formalin-fixed prostate biopsies is possible, allowing molecular studies to be performed on this valuable sample collection.
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| 14. |
- Eloranta, Sandra, et al.
(författare)
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How can we make cancer survival statistics more useful for patients and clinicians : an illustration using localized prostate cancer in Sweden
- 2013
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 24:3, s. 505-515
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Tidskriftsartikel (refereegranskat)abstract
- Studies of cancer patient survival typically report relative survival or cause-specific survival using data from patients diagnosed many years in the past. From a risk-communication perspective, such measures are suboptimal for several reasons; their interpretation is not transparent for non-specialists, competing causes of death are ignored and the estimates are unsuitable to predict the outcome of newly diagnosed patients. In this paper, we discuss the relative merits of recently developed alternatives to traditionally reported measures of cancer patient survival. In a relative survival framework, using a period approach, we estimated probabilities of death in the presence of competing risks. To illustrate the methods, we present estimates of survival among 23,353 initially untreated, or hormonally treated men with intermediate- or high-risk localized prostate cancer using Swedish population-based data. Among all groups of newly diagnosed patients, the probability of dying from prostate cancer, accounting for competing risks, was lower compared to the corresponding estimates where competing risks were ignored. Accounting for competing deaths was particularly important for patients aged more than 70 years at diagnosis in order to avoid overestimating the risk of dying from prostate cancer. We argue that period estimates of survival, accounting for competing risks, provide the tools to communicate the actual risk that cancer patients, diagnosed today, face to die from their disease. Such measures should offer a more useful basis for risk communication between patients and clinicians and we advocate their use as means to answer prognostic questions.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- Jansson, Fredrik, et al.
(författare)
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Concordance of Non-Low-Risk Disease Among Pairs of Brothers With Prostate Cancer
- 2018
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 36:18, s. 1847-1852
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Prostate cancer among first-degree relatives is a strong risk factor for diagnosis of prostate cancer, and the contribution of heritable factors in prostate cancer etiology is high. We investigated how the concordance of non-low-risk prostate cancer among brothers is affected by their genetic relation.Methods:We identified 4,262 pairs of brothers with prostate cancer in the Prostate Cancer Database Sweden. Their cancers were categorized as low risk (Gleason score 6; clinical stage T1-2, Nx/N0, Mx/M0; and prostate-specific antigen 10 ng/mL) or non-low risk. The odds ratio (OR) for concordance of non-low-risk cancer was calculated with logistic regression for the different types of fraternity (monozygotic twins, dizygotic twins, full brothers, and half-brothers)Results: Among monozygotic twins who both were diagnosed with prostate cancer, the OR for both brothers being in the non-low-risk category was 3.82 (95% CI, 0.99 to 16.72) after adjusting for age and year of diagnosis. Among full brothers, the corresponding adjusted OR was 1.21 (95% CI, 1.04 to 1.39). When the analysis was restricted to brothers who both were diagnosed within 4 years, the results were similar.Conclusion: Non-low-risk prostate cancer has a heritable pattern suggesting shared genetic factors, with the highest concordance among monozygotic twins. Our results suggest that a man whose brother has been diagnosed with a non-low-risk prostate cancer is at a clinically relevant increased risk of developing an aggressive prostate cancer himself.
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| 19. |
- Jansson, Fredrik, et al.
(författare)
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Risk of Postoperative Up Staging or Upgrading among Men with Low Risk Familial Prostate Cancer
- 2020
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Ingår i: Journal of Urology. - 0022-5347 .- 1527-3792. ; 204:1, s. 79-81
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We investigated whether men with biopsy verified, low grade cancer and a family history of lethal or advanced prostate cancer are at particularly high risk for harboring undetected high grade disease.Materials and Methods: Upgrading and up staging of prostate cancer are common after prostatectomy. In a nationwide population based cohort we identified 6,854 men with low risk prostate cancer who underwent radical prostatectomy. Among these men 1,739 (25%) had a history of prostate cancer in a first-degree relative and 289 (4%) had a first-degree relative with lethal or advanced prostate cancer.Results: Compared to men with no familial occurrence of prostate cancer, the odds ratio for the risk of up staging among men with a familial occurrence of high risk or lethal prostate cancer was 1.06 (95% CI 0.76-1.47). The corresponding odds ratio for upgrading was 1.17 (0.91-1.50).Conclusions: We found no association between family history of prostate cancer and up staging or upgrading after radical prostatectomy.
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| 20. |
- Jansson, K. Fredrik, et al.
(författare)
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Concordance of Tumor Differentiation Among Brothers with Prostate Cancer
- 2012
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Ingår i: European Urology. - Amsterdam, Netherlands : Elsevier BV. - 1873-7560 .- 0302-2838. ; 62:4, s. 656-661
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic factors seem to be of greater importance in prostate cancer than in other forms of cancer. Studies have suggested familial concordance in survival, but the extent to which that is due to tumor characteristics is not known. Objective: We hypothesized that a brother of an index case with prostate cancer is at particularly increased risk of prostate cancer with the same tumor differentiation as the index case. Design, setting and participants: We identified 21 930 brothers of index cases with prostate cancer in the Prostate Cancer Data Base Sweden and followed them up for incidence of prostate cancer. Outcome measurements and statistical analysis: The relative risk of Gleason score-specific prostate cancer in the cohort of brothers was estimated by using the standardized incidence ratio (SIR) stratified by Gleason score of the index case. We estimated 95% confidence intervals (CIs) assuming a Poisson distribution. Results and limitations: Among brothers of index cases with Gleason score 8-10 cancer, the SIR was 2.53 (95% CI, 1.97-3.21) for a Gleason score 2-6 cancer and 4.00 (95% CI, 2.63-5.82) for a Gleason score 8-10 cancer. SIR for Gleason score 2-6 cancer among brothers decreased with time since the date of the index cases' diagnoses, whereas the risk of Gleason 8-10 cancer increased over time for brothers of index cases with Gleason 8-10 cancer (p for trend = 0.009). Conclusions: Brothers of men with high-grade prostate cancer are at particularly increased risk of high-grade prostate cancer. Likewise, there is a concordance of less malignant prostate cancers within families. These findings may have direct clinical relevance for counseling men with a family history of prostate cancer. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 21. |
- Jäderling, Fredrik, et al.
(författare)
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Preoperative staging using magnetic resonance imaging and risk of positive surgical margins after prostate-cancer surgery
- 2019
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 22:3, s. 391-398
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is unclear whether preoperative staging using Magnetic Resonance Imaging (MRI) reduces the risk of positive margins in prostate cancer. We aimed to assess the effect on surgical margins and degree of nerve sparing of a pelvic MRI presented at a preoperative MRI conference. Methods: Single institution, observational cohort study including 1037 men that underwent robot assisted radical prostatectomy between October 2013 and June 2015. Of these, 557 underwent a preoperative MRI combined with a preoperative MRI conference and 410 did not. With whole-mount prostate specimen histopathology as gold standard we assessed the ability of MRI in finding the index tumor and the sensitivity and specificity for extra prostatic extension. We calculated relative risks for positive surgical margins and non-nerve sparing procedure, adjusting for preoperative risk factors using stabilized inverse-probability weighting. Results: MRI detected the index tumor in 80% of the cases. Non-organ confined disease (pT3) at histology was present in the MRI and the non-MRI group in 42% and 24%, respectively. Rate of positive surgical margins comparing the MRI and non-MRI groups was 26.7% and 33.7%, respectively, relative risk 0.79 [95% CI 0.65-0.96], weighted relative risk (wRR) 0.69 [95% CI 0.55-0.86]. The wRR of extensive positive surgical margins was 0.45 [95% CI 0.31-0.67]. Undergoing MRI was also associated with an increased risk of being operated with a non-nerve sparing technique (wRR, 1.84 [95% CI 1.11-3.03]). Conclusions: Our study suggests that preoperative prostate MRI in combination with a preoperative MRI conference affects the degree of nerve-sparing surgery and reduces positive surgical margins.
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| 22. |
- Khoshkar, Yashar, et al.
(författare)
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Mortality in men with castration‐resistant prostate cancer—A long‐term follow‐up of a population‐based real‐world cohort
- 2022
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Ingår i: BJUI Compass. - : John Wiley & Sons. - 2688-4526. ; 3:2, s. 173-183
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The objective of this study is to find clinical variables that predict the prognosis for men with castration-resistant prostate cancer (CRPC) in a Swedish real-life CRPC cohort, including a risk group classification to clarify the risk of succumbing to prostate cancer. This is a natural history cohort representing the premodern drug era before the introduction of novel hormonal drug therapies.Methods PSA tests from the clinical chemistry laboratories serving health care in six regions of Sweden were retrieved and cross-linked to the National Prostate Cancer Registry (NPCR) to identify men with a prostate cancer diagnosis. Through further cross-linking with data sources at the Swedish Board of Health and Welfare, we retrieved other relevant information such as prescribed drugs, hospitalizations, and cause of death. Men entered the CRPC cohort at the first date of doubling of their PSA nadir value with the last value being >2 ng/ml, or an absolute increase of >5 ng/ml or more, whilst on 3 months of medical castration or if they had been surgically castrated (n = 4098). By combining the two variables with the largest C-statistics, “PSA at time of CRPC” and “PSA doubling time,” a risk group classification was created.Rsults PSA-DT and PSA at date of CRPC are the strongest variables associated with PC specific survival. At the end of follow-up, the proportion of men who died due to PC was 57%, 71%, 81%, 86%, and 89% for risk categories one through five, respectively. The median overall survival in our cohort of men with CRPC was 1.86 years (95% CI: 1.79–1.97).Conclusion For a man with castration-resistant prostate cancer, there is a high probability that this will be the main cause contributing to his death. However, there is a significant difference in mortality that varies in relation to tumor burden assessed as PSA doubling time and PSA at time of CRCP. This information could be used in a clinical setting when deciding when to treat more or less aggressively once entering the CRPC phase of the disease.
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| 23. |
- Lantz, Anna, et al.
(författare)
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Functional and Oncological Outcomes After Open Versus Robot-assisted Laparoscopic Radical Prostatectomy for Localised Prostate Cancer : 8-Year Follow-up
- 2021
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 80:5, s. 650-660
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radical prostatectomy reduces mortality among patients with localised prostate cancer. Evidence on whether different surgical techniques can affect mortality rates is lacking. Objective: To evaluate functional and oncological outcomes 8 yr after robot-assisted laparoscopic prostatectomy (RALP) and open retropubic radical prostatectomy (RRP). Design, setting, and participants: We enrolled 4003 patients in a prospective, controlled, nonrandomised trial comparing RALP and RRP in 14 Swedish centres between 2008 and 2011. Data for functional outcomes were assessed via validated patient questionnaires administered preoperatively and at 12 and 24 mo and 8 yr after surgery. Outcome measurements and statistical analysis: The primary endpoint was urinary incontinence. Functional outcomes at 8 yr were analysed using the modified Poisson regression approach. Results and limitations: Urinary incontinence was not significantly different at 8 yr after surgery between RALP and RRP (27% vs 29%; adjusted risk ratio [aRR] 1.05, 95% confidence interval [CI] 0.90–1.23). Erectile dysfunction was significantly lower in the RALP group (66% vs 70%; aRR 0.93, 95% CI 0.87–0.99). Prostate cancer–specific mortality (PCSM) was significantly lower in the RALP group at 8 yr after surgery (40/2699 vs 25/885; aRR 0.56, 95% CI 0.34–0.93). Differences in oncological outcomes were mainly seen in the group with high D'Amico risk, with a lower risk of positive surgical margins (21% vs 34%), biochemical recurrence (51% vs 69%), and PCSM (14/220 vs 11/77) for RALP versus RRP. The main limitation is the nonrandomised design. Conclusions: In this prospective multicentre controlled trial, PCSM at 8 yr after surgery was lower for RALP in comparison to RRP. A causal relationship between surgical technique and mortality cannot be inferred, but the result confirms that RALP is oncologically safe. Taken together with better short-term results reported elsewhere, our findings confirm that implementation of RALP may continue. Patient summary: Our study comparing two surgical techniques for removal of the prostate for localised prostate cancer shows that a robot-assisted minimally invasive technique is safe in the long term. Together with previous results showing some better short-term effects with this approach, our findings support continued use of robot-assisted surgery.
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| 24. |
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| 25. |
- Nearchou, Andreas, et al.
(författare)
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Acquired Hypothyroidism as a Predictive Marker of Outcome in Patients With Metastatic Renal Cell Carcinoma Treated With Tyrosine Kinase Inhibitors : A Literature-Based Meta-Analysis
- 2015
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Ingår i: Clinical Genitourinary Cancer. - : Elsevier BV. - 1558-7673 .- 1938-0682. ; 13:4, s. 280-286
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Forskningsöversikt (refereegranskat)abstract
- Hypothyroidism in patients with metastatic renal cell carcinoma (mRCC) during treatment with the tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib is a well-established side effect. Furthermore, the potential role of hypothyroidism as predictive marker of outcome has been studied but with conflicting results. The aim of the present meta-analysis was to assess the predictive value of hypothyroidism for progression-free (PFS) and overall survival (OS) in patients with mRCC during TKI therapy. We searched PubMed and the electronic abstract databases of the major international congresses' proceedings to identify all eligible studies that reported a correlation between the development of hypothyroidism during TKI treatment and outcome in patients with mRCC. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were obtained from these publications and pooled in a meta-analysis. Eleven studies with a total of 500 patients fulfilled the inclusion criteria. We found no statistical significant difference in PFS between patients who developed hypothyroidism during sunitinib therapy and unaffected patients (HR, 0.82; 95% CI, 0.59-1.13; P = .22; 6 studies; 250 patients). The HR for OS was 0.52 (95% CI, 0.31-0.87; P = .01) for patients who developed hypothyroidism during sunitinib therapy compared with patients who did not (4 studies; 147 patients). The development of hypothyroidism during TKI therapy is not clearly shown to be predictive of efficacy in patients with mRCC. The observed advantage in OS for the patients with acquired hypothyroidism should be interpreted with caution.
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