| 61. |
- 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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| 62. |
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| 63. |
- Bovinder Ylitalo, Erik, et al.
(författare)
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Subgroups of castration-resistant prostate cancer bone metastases defined through an inverse relationship between androgen receptor activity and immune response
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 71:5, s. 776-787
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Tidskriftsartikel (refereegranskat)abstract
- Background: Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly for cancers not driven by androgen receptor (AR) activation. Objectives: To identify molecular subgroups of PC bone metastases of relevance for therapy.Design, setting, and participants: Fresh-frozen bone metastasis samples from men with CRPC (n = 40), treatment-naïve PC (n = 8), or other malignancies (n = 12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis. Expression profiles were verified by reverse transcription–polymerase chain reaction (RT-PCR) in an extended set of bone metastases (n = 77) and compared to levels in malignant and adjacent benign prostate tissue from patients with localized disease (n = 12). Selected proteins were evaluated using immunohistochemistry. A cohort of PC patients (n = 284) diagnosed at transurethral resection with long follow-up was used for prognostic evaluation.Results and limitations: The majority of CRPC bone metastases (80%) was defined as AR-driven based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1, HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were non–AR-driven. Functional enrichment analysis indicated high metabolic activity and low immune responses in AR-driven metastases. Accordingly, infiltration of CD3+ and CD68+ cells was lower in AR-driven than in non–AR-driven metastases, and tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear AR immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A, TAP1, and PSMB9 mRNA) in PC bone metastases compared to benign and malignant prostate tissue and bone metastases of other origins. In primary PC, low HLA class I ABC immunoreactivity was associated with high Gleason score, bone metastasis, and short cancer-specific survival. Limitations include the limited number of patients studied and the single metastasis sample studied per patient.Conclusions: Most CRPC bone metastases show high AR and metabolic activities and low immune responses. A subgroup instead shows low AR and metabolic activities, but high immune responses. Targeted therapy for these groups should be explored. Patient summary: We studied heterogeneities at a molecular level in bone metastasis samples obtained from men with castration-resistant prostate cancer. We found differences of possible importance for therapy selection in individual patients.
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| 64. |
- Brown, David A, et al.
(författare)
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Macrophage inhibitory cytokine 1 : a new prognostic marker in prostate cancer.
- 2009
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 15:21, s. 6658-6664
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: High serum levels of macrophage inhibitory cytokine 1 (MIC-1) are strongly associated with metastatic prostate cancer, suggesting MIC-1 is a biomarker for prostate cancer prognosis. EXPERIMENTAL DESIGN: We conducted a prospective cohort study of 1,442 Swedish men with a pathologically verified diagnosis of prostate cancer between 2001 and 2003. Blood was drawn either pretreatment (n = 431) or posttreatment (n = 1,011) and cases were followed for a mean time of 4.9 years (range, 0.1-6.8 years). RESULTS: MIC-1 serum levels independently predicted poor cancer-specific survival with an almost 3-fold higher cancer death rate in patients with serum levels in the highest quartile compared with men with serum levels in the lowest quartile (adjusted hazard ratio, 2.98; 95% confidence interval, 1.82-4.68). Pretreatment MIC-1 levels revealed an even stronger association with disease outcome with an 8-fold higher death rate in the highest compared with the lowest category (adjusted hazard ratio, 7.98; 95% confidence interval, 1.73-36.86). Among patients considered to have localized disease, MIC-1 significantly increased the discriminative capacity between indolent and lethal prostate cancer compared with the established prognostic markers clinical stage, pathologic grade, and prostate-specific antigen level (P = 0.016). A sequence variant in the MIC-1 gene was associated with decreased MIC-1 serum levels (P = 0.002) and decreased prostate cancer mortality (P = 0.003), suggesting a causative role of MIC-1 in prostate cancer prognosis. CONCLUSIONS: Serum MIC-1 concentration is a novel biomarker capable of predicting prostate cancer prognosis.
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| 65. |
- Crawley, Danielle, et al.
(författare)
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Association between duration and type of androgen deprivation therapy and risk of diabetes in men with prostate cancer
- 2016
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 139:12, s. 2698-2704
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Tidskriftsartikel (refereegranskat)abstract
- Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti-androgens (AA), orchiectomy, or gonadotropin-releasing hormone (GnRH) agonists compared to an age-matched, PCa-free comparison cohort (n=167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 121.5 years HR: 1.61 (95% CI: 1.36-1.91)], compared to PCa-free men. The risk decreased thereafter (e.g., 324 years HR: 1.17 (95% CI: 0.98-1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95% CI: 0.65-0.84). The incidence of T2DM per 1,000 person-years was 10 for PCa-free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM.
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| 66. |
- Crawley, Danielle, et al.
(författare)
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Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer.
- 2018
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 121:2, s. 209-216
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa.SUBJECTS AND METHODS: The Prostate Cancer database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n = 2210) for comparison with data on men with PCa only (n = 23 071). All men had intermediate- (T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20 ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL) localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate logistic regression was used to calculate the odds ratios (ORs) for receipt of curative treatment in men with and without T2DM. Overall survival, for up to 8 years of follow-up, was calculated both for men with T2DM only and for men with T2DM and PCa.RESULTS: Men with T2DM were less likely to receive curative treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69-0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and high-risk PCa who did and did not receive curative treatment, respectively.CONCLUSIONS: Men with T2DM were less likely to receive curative treatment for localized intermediate- and high-risk PCa. Men with T2DM and high-risk PCa who received curative treatment had substantially higher survival times than those who did not. Some of the survival differences represent a selection bias, whereby the healthiest patients received curative treatment. Clinicians should interpret this data carefully and ensure that individual patients with T2DM and PCa are not under- nor overtreated.
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| 67. |
- Danneman, Daniela, et al.
(författare)
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Gleason inflation 1998-2011 : a registry study of 97 168 men
- 2015
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Ingår i: BJU International. - : Wiley-Blackwell. - 1464-4096 .- 1464-410X. ; 115:2, s. 248-255
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study long-term trends in Gleason grading in a nationwide population and to assess the impact of the International Society of Urological Pathology (ISUP) revision in 2005 of the Gleason system on grading practices, as in recent years there has been a shift upwards in Gleason grading of prostate cancer. Patients and Methods: All newly diagnosed prostate cancers in Sweden are reported to the National Prostate Cancer Register (NPCR). In 97 168 men with a primary diagnosis of prostate cancer on needle biopsy from 1998 to 2011, Gleason score, clinical T stage (cT) and serum levels of prostate-specific antigen (s-PSA) at diagnosis were analysed. Results: Gleason score, cT stage and s-PSA were reported to the NPCR in 97%, 99% and 99% of cases. Before and after 2005, Gleason score 7-10 was diagnosed in 52% and 57%, respectively (P < 0.001). After standardisation for cT stage and s-PSA with 1998 as baseline these tumours increased from 59% to 72%. Among low-risk tumours (stage cT1 and s-PSA 4-10 ng/mL) Gleason score 7-10 increased from 16% in 1998 to 40% in 2011 (P trend < 0.001), mean 19% and 33% before and after 2005 (P < 0.001). Among high-risk tumours (stage T3 and s-PSA 20-50 ng/mL) Gleason score 7-10 increased from 65% in 1998 to 94% in 2011 (P trend < 0.001), mean 78% and 90% before and after 2005 (P < 0.001). A Gleason score of 2-5 was reported in 27% in 1998 and 1% in 2011. Gleason score 5 decreased sharply after 2005 and Gleason score 2-4 was almost abandoned. Conclusions: There has been a gradual shift towards higher Gleason grading, which started before 2005 but became more evident after the ISUP 2005 revision. Among low-stage tumours reporting of Gleason score 7-10 was more than doubled during the study period. When corrected for stage migration upgrading is considerable over recent decades. This has clinical consequences for therapy decisions such as eligibility for active surveillance. Grading systems need to be as stable as possible to enable comparisons over time and to facilitate the interpretation of the prognostic impact of grade.
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| 68. |
- Duggan, D., et al.
(författare)
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Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP
- 2007
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 99:24, s. 1836-1844
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Tidskriftsartikel (refereegranskat)abstract
- Background: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. Methods: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. Results: Among the approximately 60000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value =. 004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value =. 02). Conclusion: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.
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| 69. |
- 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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| 70. |
- Gedeborg, Rolf, et al.
(författare)
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An Aggregated Comorbidity Measure Based on History of Filled Drug Prescriptions : Development and Evaluation in Two Separate Cohorts
- 2021
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Ingår i: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 32:4, s. 607-615
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ability to account for comorbidity when estimating survival in a population diagnosed with cancer could be improved by using a drug comorbidity index based on filled drug prescriptions.Methods: We created a drug comorbidity index from age-stratified univariable associations between filled drug prescriptions and time to death in 326,450 control males randomly selected from the general population to men with prostate cancer. We also evaluated the index in 272,214 control females randomly selected from the general population to women with breast cancer.Results: The new drug comorbidity index predicted survival better than the Charlson Comorbidity Index (CCI) and a previously published prescription index during 11 years of follow-up. The concordance (C)-index for the new index was 0.73 in male and 0.76 in the female population, as compared with a C-index of 0.67 in men and 0.69 in women for the CCI. In men of age 75-84 years with CCI = 0, the median survival time was 7.1 years (95% confidence interval [CI] = 7.0, 7.3) in the highest index quartile. Comparing the highest to the lowest drug comorbidity index quartile resulted in a hazard ratio (HR) of 2.2 among men (95% CI = 2.1, 2.3) and 2.4 among women (95% CI = 2.3, 2.6).Conclusions: A new drug comorbidity index based on filled drug prescriptions improved prediction of survival beyond age and the CCI alone. The index will allow a more accurate baseline estimation of expected survival for comparing treatment outcomes and evaluating treatment guidelines in populations of people with cancer.
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