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  • 51. Marconi, Lorenzo
    et al.
    Dabestani, Saeed
    Lam, Thomas B.
    Hofmann, Fabian
    Stewart, Fiona
    Norrie, John
    Bex, Axel
    Bensalah, Karim
    Canfield, Steven E.
    Hora, Milan
    Kuczyk, Markus A.
    Merseburger, Axel S.
    Mulders, Peter F. A.
    Powles, Thomas
    Staehler, Michael
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Volpe, Alessandro
    Systematic Review and Meta-analysis of Diagnostic Accuracy of Percutaneous Renal Tumour Biopsy2016Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, nr 4, s. 660-673Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Context: The role of percutaneous renal tumour biopsy (RTB) remains controversial due to uncertainties regarding its diagnostic accuracy and safety.

    Objective: We performed a systematic review and meta-analysis to determine the safety and accuracy of percutaneous RTB for the diagnosis of malignancy, histologic tumour subtype, and grade.

    Evidence acquisition: Medline, Embase, and Cochrane Library were searched for studies providing data on diagnostic accuracy and complications of percutaneous core biopsy (CB) or fine-needle aspiration (FNA) of renal tumours. A meta-analysis was performed to obtain pooled estimates of sensitivity and specificity for diagnosis of malignancy. The Cohen kappa coefficient (κ) was estimated for the analysis of histotype/grade concordance between diagnosis on RTB and surgical specimen. Risk of bias assessment was performed (QUADAS-2).

    Evidence synthesis: A total of 57 studies recruiting 5228 patients were included. The overall median diagnostic rate of RTB was 92%. The sensitivity and specificity of diagnostic CBs and FNAs were 99.1% and 99.7%, and 93.2% and 89.8%, respectively. A good (κ = 0.683) and a fair (κ = 0.34) agreement were observed between histologic subtype and Fuhrman grade on RTB and surgical specimen, respectively. A very low rate of Clavien ≥2 complications was reported. Study limitations included selection and differential-verification bias.

    Conclusions: RTB is safe and has a high diagnostic yield in experienced centres. Both CB and FNA have good accuracy for the diagnosis of malignancy and histologic subtype, with better performance for CB. The accuracy for Fuhrman grade is fair. Overall, the quality of the evidence was moderate. Prospective cohort studies recruiting consecutive patients and using homogeneous reference standards are required.

    Patient summary: We systematically reviewed the literature to assess the safety and diagnostic performance of renal tumour biopsy (RTB). The results suggest that RTB has good accuracy in diagnosing renal cancer and its subtypes, and it appears to be safe. However, the quality of evidence was moderate, and better quality studies are required to provide a more definitive answer.

  • 52. Marconi, Lorenzo
    et al.
    Lam, Thomas B.
    Bex, Axel
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Volpe, Alessandro
    Reply to E. Jason Abel Letter to the Editor re: Lorenzo Marconi, Saeed Dabestani, Thomas B. Lam, et al. Systematic Review and Meta-analysis of Diagnostic Accuracy of Percutaneous Renal Tumour Biopsy. Eur Urol 2016;69:660-732016Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, nr 6, s. E119-E120Artikkel i tidsskrift (Fagfellevurdert)
  • 53. Marconi, Lorenzo
    et al.
    Lam, Thomas B.
    Bex, Axel
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Volpe, Alessandro
    Reply to Jae Heon Kim's Letter to the Editor re: Lorenzo Marconi, Saeed Dabestani, Thomas B. Lam, et al. Systematic Review and Meta-analysis of Diagnostic Accuracy of Percutaneous Renal Tumour Biopsy. Eur Urol 2016; 69: 660-732016Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 5, s. E141-E142Artikkel i tidsskrift (Fagfellevurdert)
  • 54.
    Ohlson, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nygren, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    The magnitude of early castration-induced primary tumour regression in prostate cancer does not predict clinical outcome2006Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 49, nr 4, s. 675-683Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: This study was designed to test whether early castration-induced short-term cellular changes in primary prostate tumours could predict clinical outcome in advanced disease. PATIENTS AND METHODS: Biopsies from 83 patients obtained before and within two weeks after surgical castration were investigated. Tumour epithelial cell apoptosis, proliferation, and prostate specific antigen (PSA) levels were quantified using immunohistochemistry, laser capture micro-dissection, and real time RT-PCR. Cellular effects were related to changes in serum PSA levels and clinical outcome. RESULTS: Decreased proliferation and PSA mRNA levels, and increased apoptosis were observed in most tumours. These early cellular responses were not correlated to each other and did not predict serum PSA response or cancer-specific survival. A nadir PSA level below 1 ng/ml predicted a longer cancer-specific survival after castration therapy. CONCLUSION: Castration therapy causes primary tumour regression in most patients with advanced prostate cancer, but these primary tumour effects are not predictive for systemic disease control. Studies of early changes in metastases during hormonal therapy will probably give more predictive information for clinical outcome than further studies in primary tumours.

  • 55. Parker, Christopher C.
    et al.
    Coleman, Robert E.
    Sartor, Oliver
    Vogelzang, Nicholas J.
    Bottomley, David
    Heinrich, Daniel
    Helle, Svein I.
    O'Sullivan, Joe M.
    Fosså, Sophie D.
    Chodacki, Aleš
    Wiechno, Paweł
    Logue, John
    Seke, Mihalj
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johannessen, Dag Clement
    Hoskin, Peter
    James, Nicholas D.
    Solberg, Arne
    Syndikus, Isabel
    Kliment, Jan
    Wedel, Steffen
    Boehmer, Sibylle
    Dall'Oglio, Marcos
    Franzén, Lars
    Bruland, Øyvind S.
    Petrenciuc, Oana
    Staudacher, Karin
    Li, Rui
    Nilsson, Sten
    Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial2018Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, nr 3, s. 427-435Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment. Objective: To report updated ALSYMPCA safety, including long-term safety up to 3 yr after the first injection. Design, setting, and participants: Safety analyses from phase 3 randomized ALSYMPCA trial included patients receiving >= 1 study-drug injection (600 radium-223 and 301 placebo). Patients (405 radium-223 and 167 placebo) entered long-term safety follow-up starting 12 wk after the last study-drug injection, to 3 yr from the first injection. Forty-eight of 405 (12%) radium-223 and 12/167 (7%) placebo patients completed follow-up, with evaluations every 2 mo for 6 mo, then every 4 mo until 3 yr. Outcome measurements and statistical analysis: All adverse events (AEs) were collected until 12 wk after the last injection; subsequently, only treatment-related AEs were collected. Additional long-term safety was assessed by development of acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia, and secondary malignancies. Data analysis used descriptive statistics. Results and limitations: During treatment to 12 wk following the last injection, 564/600 (94%) radium-223 and 292/301 (97%) placebo patients had treatment-emergent AEs (TEAEs). Myelosuppression incidence was low. Grade 3/4 hematologic TEAEs in radium-223 and placebo groups were anemia (13% vs 13%), neutropenia (2% vs 1%), and thrombocytopenia (7% vs 2%). Ninety-eight of 600 (16%) radium-223 and 68/301 (23%) placebo patients experienced grade 5 TEAEs. Long-term follow-up showed no AML, MDS, or new primary bone cancer; secondary non-treatment-related malignancies occurred in four radium-223 and three placebo patients. One radium-223 patient had aplastic anemia 16 mo after the last injection. No other cases were observed. Limitations include short (3-yr) follow-up. Conclusions: Final long-term safety ALSYMPCA analysis shows that radium-223 remained well tolerated, with low myelosuppression incidence and no new safety concerns.

  • 56. Plym, Anna
    et al.
    Chiesa, Flaminia
    Voss, Margaretha
    Holmberg, Lars
    Johansson, Eva
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Urology, Uppsala University Hospital, Uppsala, Sweden.
    Lambe, Mats
    Work Disability After Robot-assisted or Open Radical Prostatectomy: A Nationwide, Population-based Study2016Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 1, s. 64-71Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Robot-assisted radical prostatectomy (RARP) has been associated with reduced bleeding and shorter hospital stays than open retropubic radical prostatectomy (RRP), but it is unclear whether these differences translate into shorter absence from work. Objective: To investigate short-and long-term rates of work disability following RARP and RRP. Design, setting, and participants: We conducted a nationwide population-based cohort study of 2571 men of working age treated with RARP or RRP between 2007 and 2009 identified in the National Prostate Cancer Register of Sweden. Information about physician-certified sick leave and disability pension was retrieved from the Swedish Social Insurance Agency through 2012. Outcome measurements and statistical analysis: We used Cox regression to calculate time to return to work (RTW, or duration of sick leave) after surgery and used generalised estimating equations to analyse days lost from work (because of sick leave and disability pension) after RTW. Results and limitations: Men treated with RARP returned to work after a median of 35 d, whereas the corresponding time for RRP was 48 d (p < 0.001). The difference was seen early; within the first month, men treated with RARP returned to work nearly four times faster than men treated with RRP (adjusted relative RTW rate 3.76; 95% confidence interval [CI], 3.04-4.66). During a median of 3.6 yr after return to work, men treated with RARP lost fewer days from work per person-year than men treated with RRP-12 d versus 15 d-but the association was not statistically significant (p = 0.10). The adjusted rate ratio was 1.08 (95% CI, 0.82-1.42). One limitation is the nonrandomised design of this study. Conclusions: RARP was associated with a faster RTW compared with RRP, but the surgical method did not influence long-term rates of work disability in terms of days lost from work after RTW. Patient summary: We compared disease-related absence from work between two surgical methods for the removal of the prostate. Robot-assisted surgery was associated with a faster return to work compared with open surgery but did not influence absence from work in a long-term perspective. 

  • 57. Plym, Anna
    et al.
    Voss, Margaretha
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Urology, Uppsala University Hospital, Uppsala, Sweden.
    Lambe, Mats
    Reply from Authors re: Matthew T. Gettman. Assessing Work Disability After Radical Prostatectomy. Eur Urol 2016;70:72-3 The Challenge of Assessing Work Disability2016Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 1, s. 73-74Artikkel i tidsskrift (Annet vitenskapelig)
  • 58. Powles, Thomas
    et al.
    Albiges, Laurence
    Staehler, Michael
    Bensalah, Karim
    Dabestani, Saeed
    Giles, Rachel H.
    Hofmann, Fabian
    Hora, Milan
    Kuczyk, Markus A.
    Lam, Thomas B.
    Marconi, Lorenzo
    Merseburger, Axel S.
    Fernández-Pello, Sergio
    Tahbaz, Rana
    Volpe, Alessandro
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bex, Axel
    Updated European Association of Urology Guidelines: Recommendations for the Treatment of First-line Metastatic Clear Cell Renal Cancer2018Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, nr 3, s. 311-315Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The randomised phase III clinical trial Checkmate-214 showed a survival superiority for the combination of ipilimumab and nivolumab when compared with the previous standard of care in first-line metastatic/advanced clear cell renal cell carcinoma (RCC) (Escudier B, Tannir NM, McDermott DF, et al. CheckMate 214: efficacy and safety of nivolumab plus ipilimumab vs sunitinib for treatment-naive advanced or metastatic renal cell carcinoma, including IMDC risk and PD-L1 expression subgroups. LBA5, ESMO 2017, 2017). These results change the frontline standard of care for this disease and have implications for the selection of subsequent therapies. For this reason the European Association of Urology RCC guidelines have been updated. Patient summary: The European Association of Urology guidelines will be updated based on the results of the phase III Checkmate-214 clinical trial. The trial showed superior survival for a combination of ipilimumab and nivolumab (IN), compared with the previous standard of care, in intermediate-and poor-risk patients with metastatic clear cell renal cell carcinoma. When IN is not safe or feasible, alternative agents such as sunitinib, pazopanib, and cabozantinib should be considered. Furthermore, at present, the data from the trial are immature in favourable-risk patients. Therefore, sunitinib or pazopanib remains the favoured agent for this subgroup of patients.

  • 59. Powles, Thomas
    et al.
    Staehler, Michael
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bensalah, Karim
    Canfield, Steven E.
    Dabestani, Saeed
    Giles, Rachel H.
    Hofmann, Fabian
    Hora, Milan
    Kuczyk, Markus A.
    Lam, Thomas
    Marconi, Lorenzo
    Merseburger, Axel S.
    Volpe, Alessandro
    Bex, Axel
    European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy2016Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 5, s. 705-706Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The European Association of Urology renal cancer guidelines panel recommends nivolumab and cabozantinib over the previous standard of care in patients who have failed one or more lines of vascular endothelial growth factor-targeted therapy. New data have recently become available showing a survival benefit for cabozantinib.

  • 60. Powles, Thomas
    et al.
    Staehler, Michael
    Ljungberg, Börje
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Bensalah, Karim
    Canfield, Steven E.
    Dabestani, Saeed
    Giles, Rachel
    Hofmann, Fabian
    Hora, Milan
    Kuczyk, Markus A.
    Lam, Thomas
    Marconi, Lorenzo
    Merseburger, Axel S.
    Volpe, Alessandro
    Bex, Axel
    Updated EAU Guidelines for Clear Cell Renal Cancer Patients Who Fail VEGF Targeted Therapy2016Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, nr 1, s. 4-6Artikkel i tidsskrift (Annet vitenskapelig)
  • 61. Price, Alison J
    et al.
    Travis, Ruth C
    Appleby, Paul N
    Albanes, Demetrius
    Barricarte Gurrea, Aurelio
    Bjørge, Tone
    Bueno-de-Mesquita, H Bas
    Chen, Chu
    Donovan, Jenny
    Gislefoss, Randi
    Goodman, Gary
    Gunter, Marc
    Hamdy, Freddie C
    Johansson, Mattias
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. International Agency for Research on Cancer, Lyon, France.
    King, Irena B
    Kühn, Tilman
    Männistö, Satu
    Martin, Richard M
    Meyer, Klaus
    Neal, David E
    Neuhouser, Marian L
    Nygård, Ottar
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Tell, Grethe S
    Trichopoulou, Antonia
    Tumino, Rosario
    Ueland, Per Magne
    Ulvik, Arve
    de Vogel, Stefan
    Vollset, Stein Emil
    Weinstein, Stephanie J
    Key, Timothy J
    Allen, Naomi E
    Circulating Folate and Vitamin B12 and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls2016Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 6, s. 941-951Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Folate and vitamin B12 are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear.

    OBJECTIVE: To investigate the associations between circulating folate and vitamin B12 concentrations and risk of PCa overall and by disease stage and grade.

    DESIGN, SETTING, AND PARTICIPANTS: A study was performed with a nested case-control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B12 were calculated using multivariable adjusted conditional logistic regression.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incident PCa and subtype by stage and grade.

    RESULTS AND LIMITATIONS: Higher folate and vitamin B12 concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02-1.26], ptrend=0.018, for folate and 1.12 [95% CI, 1.01-1.25], ptrend=0.017, for vitamin B12), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (pheterogeneity<0.001); higher folate concentration was associated with an elevated risk of high-grade disease (OR for the top vs bottom fifth: 2.30 [95% CI, 1.28-4.12]; ptrend=0.001), with no association for low-grade disease. There was no evidence of heterogeneity in the association of folate with risk by stage or of vitamin B12 with risk by stage or grade of disease (pheterogeneity>0.05). Use of single blood-sample measurements of folate and B12 concentrations is a limitation.

    CONCLUSIONS: The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation.

    PATIENT SUMMARY: Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease.

  • 62. Rider, Jennifer R.
    et al.
    Sandin, Fredrik
    Andren, Ove
    Wiklund, Peter
    Hugosson, Jonas
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Long-term outcomes among noncuratively treated men according to Prostate Cancer risk category in a nationwide, population-based study2013Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, nr 1, s. 88-96Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Limited data exist on long-term outcomes among men with prostate cancer (PCa) from population-based cohorts incorporating information on clinical risk category. Objective: To assess 15-yr mortality for men with PCa treated with noncurative intent according to clinical stage, Gleason score (GS), serum levels of prostate specific antigen (PSA), comorbidity, and age. Design, setting, and participants: Register-based cohort study of 76 437 cases in the National Prostate Cancer Register (NPCR) of Sweden diagnosed from 1991 through 2009 and treated with noncurative intent. Each case was placed in one of five risk categories: (1) low risk: T1-T2 tumor, PSA level <10 ng/ml, and GS <= 6; (2) intermediate risk: T1-T2 tumor and PSA level 10-<20 ng/ml or GS 7; (3) high risk: T3 tumor or PSA level 20-<50 ng/ml or GS >= 8; (4) regional metastases: N1 or T4 tumor or PSA level 50-100 ng/ml; and (5) distant metastases: M1 tumor or PSA >= 100 ng/ml. Outcome measurements and statistical analysis: Ten-and 15-yr cumulative risk of death after diagnosis from PCa, cardiovascular disease, and other causes. Results and limitations: Among men with a Charlson Comorbidity Index (CCI) score of 0, no differences were found in observed versus expected all-cause mortality in the low-risk group. Observed mortality was only slightly greater in the intermediate-risk group, but men with high-risk localized PCa or more advanced disease had substantially higher mortality than expected. CCI was strongly associated with cumulative 10-yr mortality from causes other than PCa, especially for men <65 yr. Limitations include potential misclassification in risk category due to GS assignment. Conclusions: PCa mortality rates vary 10-fold according to risk category. The risk of death from causes other than PCa is most strongly related to comorbidity status in younger men. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.

  • 63. Robinson, David
    et al.
    Garmo, Hans
    Lissbrant, Ingela Franck
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Pettersson, Andreas
    Gunnlaugsson, Adalsteinn
    Adolfsson, Jan
    Bratt, Ola
    Nilsson, Per
    Stattin, Pär
    Prostate Cancer Death After Radiotherapy or Radical Prostatectomy: A Nationwide Population-based Observational Study2018Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, nr 4, s. 502-511Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There are no conclusive results from randomized trials on radiotherapy (RT) versus radical prostatectomy (RP) for prostate cancer. Numerous observational studies have suggested that RP is associated with a lower risk of prostate cancer death, but whether results have been biased due to limited adjustments for confounding factors is unknown.

    Objective: To compare the risk of prostate cancer death after RT versus RP.

    Design, setting, and participants: Nationwide population-based observational study of men in the Prostate Cancer data Base Sweden 3.0 who had undergone RT or RP between 1998 and 2012.

    Outcome measurements and statistical analysis: Prostate cancer deaths were compared. Hazard ratios (HRs) were calculated in Cox regression models, including clinical T stage, M stage, Gleason grade group, serum levels of prostate-specific antigen, proportion of biopsy cores with cancer, mode of detection, comorbidity, age, educational level, and civil status. Period analysis with left truncation was performed.

    Results and limitations: Primary treatment was RT or RP for 41 503 men. Treatment effect was associated with disease severity. In univariate analysis of RT versus RP, risk of prostate cancer death was higher after RT-low-and intermediate-risk cancer, HR 1.82 (95% confidence interval [CI]: 1.53-2.16), and high-risk cancer, HR 1.57 (95% CI: 1.33-1.85). After full adjustment in period analysis, this difference between the treatments was attenuated-low-and intermediate-risk cancer, HR 1.24 (95% CI: 0.97-1.58), and high-risk cancer, HR 1.03 (95% CI: 0.81-1.31). Confounding remained due to nonrandom allocation to treatment.

    Conclusions: In comparison with previous studies, the difference in prostate cancer mortality after RT and RP was much smaller.

    Patient summary: The difference in prostate cancer mortality after contemporary radiotherapy and radical prostatectomy was small in contrast to previous studies, indicating that potential side effects should be more emphasized when selecting treatment.

  • 64. Shui, Irene M.
    et al.
    Lindstroem, Sara
    Kibel, Adam S.
    Berndt, Sonja I.
    Campa, Daniele
    Gerke, Travis
    Penney, Kathryn L.
    Albanes, Demetrius
    Berg, Christine
    Bueno-de-Mesquita, H. Bas
    Chanock, Stephen
    Crawford, E. David
    Diver, W. Ryan
    Gapstur, Susan M.
    Gaziano, J. Michael
    Giles, Graham G.
    Henderson, Brian
    Hoover, Robert
    Johansson, Mattias
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. q International Agency for Research on Cancer, Lyon, France.
    Le Marchand, Loic
    Ma, Jing
    Navarro, Carmen
    Overvad, Kim
    Schumacher, Fredrick R.
    Severi, Gianluca
    Siddiq, Afshan
    Stampfer, Meir
    Stevens, Victoria L.
    Travis, Ruth C.
    Trichopoulos, Dimitrios
    Vineis, Paolo
    Mucci, Lorelei A.
    Yeager, Meredith
    Giovannucci, Edward
    Kraft, Peter
    Prostate Cancer (PCa) Risk Variants and Risk of Fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium2014Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 65, nr 6, s. 1069-1075Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM). Objective: To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM. Design, setting, and participants: We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred. Outcome measurements and statistical analysis: The main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls. Results and limitations: Among the cases, we found that 8 of the 47 SNPs were significantly associated (p < 0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p < 0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only. Conclusions: Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa. Patient summary: In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 65. Sooriakumaran, Prasanna
    et al.
    Nyberg, Tommy
    Akre, Olof
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Hamdy, Freddie
    Graefen, Markus
    Carlsson, Stefan
    Steineck, Gunnar
    Wiklund, N. Peter
    Survival Among Men at High Risk of Disseminated Prostate Cancer Receiving Initial Locally Directed Radical Treatment or Initial Androgen Deprivation Therapy2017Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, nr 3, s. 345-351Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There is increasing low-quality evidence rationalizing the use of radical therapy for men at high risk of disseminated prostate cancer. Objective: To investigate, using high-quality epidemiologic data, whether initial radical therapy in men at high risk of disseminated prostate cancer improves survival. Design, setting, and participants: An observational population-based Swedish study from 1996 to 2010 of men at high risk of disseminated prostate cancer (prostate-specific antigen [PSA] > 50) initially treated by radical therapy (radiation therapy [n = 630] or radical prostatectomy [n = 120]) or androgen deprivation therapy (n = 17 602), and followed for up to 15 yr. Outcome measurements and statistical analysis: Prostate-cancer and other-cause mortality was estimated for the treatment groups. We also matched the two cohorts for grade, T stage, M stage, Charlson score, year of diagnosis, age, and PSA, and found androgen deprivation therapy patient matches for 575 of the radical therapy patients, and then repeated comparative effectiveness analyses. Results and limitation: Prostate-cancer mortality was substantially greater in the androgen deprivation therapy group compared with the radically treated one, in unmatched (9062/17 602 vs 86/750) and matched (177/575 vs 71/575) cohorts. Among matched cohorts, initial androgen deprivation therapy was associated with nearly three-fold higher hazard of prostate-cancer death compared with initial radical therapy (2.87; 95% confidence interval 2.16-3.82). Multiple sensitivity analyses suggested that the findings were robust, although the general limitations of nonrandomized studies remain. Further, the study cohort may have included men with both systemic and nonsystemic disease, as a sole eligibility criterion of PSA > 50 was used. Conclusions: This large and comprehensive population-based study suggests that initial radical therapy in men at high risk of disseminated prostate cancer improves survival. Patient summary: This large Swedish study suggests that men with prostate cancer that has spread beyond the prostate benefit from treating the prostate itself with radiation therapy or surgery rather than treating the disease with hormones alone.

  • 66.
    Stattin, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Centre, New York, NY, USA.
    Loeb, Stacy
    Department of Urology, New York University and Manhattan Veterans Affairs Medical Centre, New York, NY, USA.
    "To Measure Is To Know. If You Cannot Measure It, You Cannot Improve It'': Statistical Modeling Cannot Compensate for Unmeasured Bias2014Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 65, nr 4, s. 701-703Artikkel i tidsskrift (Annet vitenskapelig)
  • 67.
    Stattin, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Robinson, David
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Lambe, Mats
    Uppsala University Hospital, Regional Cancer Center, Uppsala, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Re: Giorgio Gandaglia, Freddie Bray, Matthew R. Cooperberg, et al.: Prostate Cancer Registries: Current Status and Future Directions. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.05.0462015Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, nr 5, s. E110-E110Artikkel i tidsskrift (Fagfellevurdert)
  • 68.
    Stattin, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Sandin, Fredrik
    Birkebæk Thomsen, Frederik
    Garmo, Hans
    Robinson, David
    Franck Lissbrant, Ingela
    Jonsson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Bratt, Ola
    Association of Radical Local Treatment with Mortality in Men with Very High-risk Prostate Cancer: A Semiecologic, Nationwide, Population-based Study2017Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, nr 1, s. 125-134Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Current guidelines recommend androgen deprivation therapy only for men with very high-risk prostate cancer (PCa), but there is little evidence to support this stance.

    Objective: To investigate the association between radical local treatment and mortality in men with very high-risk PCa.

    Design, setting, and participants: Semiecologic study of men aged <80 yr within the Prostate Cancer data Base Sweden, diagnosed in 1998–2012 with very high-risk PCa (local clinical stage T4 and/or prostate-specific antigen [PSA] level 50–200 ng/ml, any N, and M0). Men with locally advanced PCa (local clinical stage T3 and PSA level <50 ng/ml, any N, and M0) were used as positive controls.

    Intervention: Proportion of men who received prostatectomy or full-dose radiotherapy in 640 experimental units defined by county, diagnostic period, and age at diagnosis.

    Outcome measurements and statistical analysis: PCa and all-cause mortality rate ratios (MRRs).

    Results and limitations: Both PCa and all-cause mortality were half as high in units in the highest tertile of exposure to radical local treatment compared with units in the lowest tertile (PCa MRR: 0.51; 95% confidence interval [CI], 0.28–0.95; and all-cause MRR: 0.56; 95% CI, 0.33–0.92). The results observed for locally advanced PCa for highest versus lowest tertile of exposure were in agreement with results from randomized trials (PCa MRR: 0.75; 95% CI, 0.60–0.94; and all-cause MRR: 0.85; 95% CI, 0.72–1.00). Although the semiecologic design minimized selection bias on an individual level, the effect of high therapeutic activity could not be separated from that of high diagnostic activity.

    Conclusions: The substantially lower mortality in units with the highest exposure to radical local treatment suggests that radical treatment decreases mortality even in men with very high-risk PCa for whom such treatment has been considered ineffective.

    Patient summary: Men with very high-risk prostate cancer diagnosed and treated in units with the highest exposure to surgery or radiotherapy had a substantially lower mortality.

  • 69.
    Stattin, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Sandin, Fredrik
    Reg Canc Ctr, Uppsala, Sweden.
    Hugosson, Jonas
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden.
    Reply from authors re: Urs E. Studer, Peter C. Albertsen. It's Time to Change the Treatment Paradigm for Prostate Cancer! Eur Urol 2013;63:97-9 PCBaSe Sweden combines the National Prostate Cancer Register of Sweden with Health Care Registers and Demographic Databases: A useful tool for observational studies2013Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, nr 1, s. 99-100Artikkel i tidsskrift (Annet vitenskapelig)
  • 70.
    Stattin, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Vickers, Andrew J.
    New York, NY, USA.
    Sjoberg, Daniel D.
    New York, NY, USA.
    Johansson, Robert
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Granfors, Torvald
    Stockholm, Sweden.
    Johansson, Mattias
    Section of Genetics, The International Agency for Research on Cancer, Lyon, France.
    Pettersson, Kim
    Turku, Finland.
    Scardino, Peter T.
    New York, NY, USA.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Lilja, Hans
    New York, NY, USA; Headington, Oxford, UK; Malmö, Sweden.
    Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: a Nested Case-Control Study2015Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, nr 2, s. 207-213Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death. Objective: To increase the specificity of screening for lethal PCa at an early stage. Design, setting, and participants: We conducted a case-control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Vasterbotten, Sweden. Of 40 379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12 542 men were followed for > 15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis. Outcome measurements and statistical analysis: Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers. Results and limitations: Mostmetastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (<= 0.6%). Among men with PSA > 2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA > 2 ng/ml were defined as low risk by this model and had a <= 1% 15-yr risk of metastasis. Conclusions: Screening at ages 50-60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making. Patient summary: For men in their fifties, screening should focus on those in the top 10% to 25% of PSA values because the majority of subsequent cases of distant metastasis are found among these men. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making.

  • 71.
    Thysell, Elin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ylitalo, Erik B.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jernberg, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Reply to Isabel Heidegger, Renate Pichler, and Andreas Pircher's Letter to the Editor re: Erik Bovinder Ylitalo, Elin Thysell, Emma Jernberg, et al. Subgroups of Castration-resistant Prostate Cancer Bone Metastases Defined Through an Inverse Relationship Between Androgen Receptor Activity and Immune Response. Eur Urol 2017;71:776-872017Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, nr 4, s. e104-e105Artikkel i tidsskrift (Fagfellevurdert)
  • 72.
    Thysell, Elin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Ylitalo, Erik B.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Jernberg, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wikström, Pernilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Reply to Isabel Heidegger, Renate Pichler, and Andreas Pircher's Letter to the Editor re: Erik Bovinder Ylitalo, Elin Thysell, Emma Jernberg, et al. Subgroups of Castration-resistant Prostate Cancer Bone Metastases Defined Through an Inverse Relationship Between Androgen Receptor Activity and Immune Response. Eur Urol 2017;71:776-872017Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, nr 4, s. E104-E105Artikkel i tidsskrift (Fagfellevurdert)
  • 73. Van Hemelrijck, Mieke
    et al.
    Garmo, Hans
    Adolfsson, Jan
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Re: Adi J. Klil-Drori, Hui Yin, Vicky Tagalakis, Armen Aprikian, Laurent Azoulay. Androgen Deprivation Therapy for Prostate Cancer and Risk of Venous Thromboembolism Eur Urol 2016;70:56-612017Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, nr 2, s. E61-E62Artikkel i tidsskrift (Fagfellevurdert)
  • 74. Van Hemelrijck, Mieke
    et al.
    Garmo, Hans
    Holmberg, Lars
    Bill-Axelson, Anna
    Carlsson, Stefan
    Akre, Olof
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Adolfsson, Jan
    Thromboembolic events following surgery for prostate cancer2013Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, nr 2, s. 354-363Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Prostate cancer (PCa) and surgery are both associated with increased risk of thromboembolic diseases (TED). Objective: We assessed risk of TED among men undergoing different types of urologic surgery. Design, setting, and participants: Using the Prostate Cancer Database Sweden (PCBaSe) Sweden, we identified all men (n = 45 065) undergoing pelvic lymph node dissection (PLND), radical prostatectomy (RP) with or without PLND, orchiectomy due to PCa, or a transurethral resection of the prostate (TURP). We identified a comparison cohort from the population. Outcome measurements and statistical analysis: Main outcomes were deep venous thrombosis (DVT) and pulmonary embolism (PE) as primary diagnoses in the National Patient Register or Cause of Death Register (2002-2010). We calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable Cox proportional hazards models. Results and limitations: All surgical procedures were associated with increased risk of TED; laparoscopic and open RP with a PLND were the most strongly associated with TED (HR for PE: 8.1 [95% CI, 2.9-23.0] and 7.8 [95% CI, 4.9-13], respectively). For surgery including a PLND, the risk increased during the second half of the first postoperative month. The HR for PE after TURP in men with PCa was 3.0 (95% CI, 1.8-5.1). Patients with a history of TED had a strongly increased risk of TED (HR for DVT: 4.5; 95% CI, 2.6-8.0). A limitation is lack of information on TED prophylaxis, but its use was standardized during the study period for RP and PLND. Other limitations are lack of information on extent of PLND and lifestyle factors. Conclusions: Surgeries for PCa, including TURP, are associated with hospitalization for TED. Patients with a history of TED and patients undergoing a PLND were at highest risk. The largest risk was observed from days 14 to 28 postoperatively. Thus, our results suggest that prophylactic measures may be beneficial during the first 4 wk in these patients. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.

  • 75. Van Hemelrijck, Mieke
    et al.
    Garmo, Hans
    Holmberg, Lars
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Adolfsson, Jan
    Multiple events of fractures and cardiovascular and thromboembolic disease following prostate cancer diagnosis: results from the population-based PCBaSe Sweden2012Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 61, nr 4, s. 690-700Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: To date, adverse events of prostate cancer (PCa) treatment have only been studied as a single event, and little is known about the risk of subsequent adverse events.

    OBJECTIVE: We assessed the frequency of multiple events (fractures, stroke, heart disease [HD], and thromboembolic disease [TED]) following PCa diagnosis.

    DESIGN, SETTING, AND PARTICIPANTS: PCBaSe Sweden is based on the National Prostate Cancer Register (NPCR) that covers >96% of incident PCa cases in Sweden.

    MEASUREMENTS: We evaluated the number of events (fractures, stroke, HD, and TED) leading to hospitalisation recorded in the National Hospital Discharge Registry after PCa diagnosis and conducted multivariate age-adjusted Cox proportional hazards regression to estimate the risk of developing multiple events.

    RESULTS AND LIMITATIONS: Between 1997 and 2007, 30 642 men received primary endocrine treatment, 26 432 curative treatment, and 19 526 surveillance: 75% had no event during follow-up, 17% had one event, and 9% had more than one event. The incidence of any event was 102 in 1000 person-years. Men who already had experienced an event, particularly HD, before or after the date of PCa diagnosis were more likely to have multiple events afterwards. For example, the hazard ratio of developing a third event for those with two or more events of HD before PCa diagnosis was 1.40 (95% confidence interval, 1.28-1.52) compared with those with no events of HD before PCa diagnosis. Events treated without hospitalisation were not included, so the number of adverse events is possibly underestimated.

    CONCLUSIONS: A third of PCa patients with an adverse event after treatment subsequently experienced another adverse event, but apart from history of HD or stroke before PCa diagnosis, no specific characteristics were found for these men. Thus PCa management needs to take into account the risk of adverse events in all PCa patients, especially those with a history of adverse events before PCa diagnosis.

  • 76. Van Hemelrijck, Mieke
    et al.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Adolfsson, Jan
    Reply from authors re: Matthew R. Cooperberg. Adverse effects of androgen deprivation and the limits of national tumor registries. Eur Urol. 2012;61:701–3, DOI 10.1016/j.eururo.2011.09.0102012Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 61, nr 4, s. 703-704Artikkel i tidsskrift (Annet vitenskapelig)
  • 77. Van Hemelrijck, Mieke
    et al.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Adolfsson, Jan
    Reply to Tommaso Cai, Carolina D'Elia, and Beatrice Detti's letter to the editor re: Mieke Van Hemelrijck, Hans Garmo, Lars Holmberg, et al. Multiple events of fractures and cardiovascular and thromboembolic disease following prostate cancer diagnosis: results from the population-based PCBaSe Sweden. Eur Urol 2012;61:690–7002012Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 61, nr 4, s. e28-Artikkel i tidsskrift (Annet vitenskapelig)
  • 78. Walker, Steven M
    et al.
    Knight, Laura A
    McCavigan, Andrena M
    Logan, Gemma E
    Berge, Viktor
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Pandha, Hardev
    Warren, Anne Y
    Davidson, Catherine
    Uprichard, Adam
    Blayney, Jaine K
    Price, Bethanie
    Jellema, Gera L
    Steele, Christopher J
    Svindland, Aud
    McDade, Simon S
    Eden, Christopher G
    Foster, Chris
    Mills, Ian G
    Neal, David E
    Mason, Malcolm D
    Kay, Elaine W
    Waugh, David J
    Harkin, D Paul
    Watson, R William
    Clarke, Noel W
    Kennedy, Richard D
    Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology2017Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, nr 4, s. 509-518Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy.

    OBJECTIVE: To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy.

    DESIGN, SETTING, AND PARTICIPANTS: Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis.

    RESULTS AND LIMITATIONS: A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; p<0.0001 and HR=7.53 [4.13-13.73]; p<0.0001, respectively). The retrospective nature of the study is acknowledged as a potential limitation.

    CONCLUSIONS: The metastatic assay may identify a molecular subgroup of primary prostate cancers with metastatic potential.

    PATIENT SUMMARY: The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population.

  • 79. Witjes, J. Alfred
    et al.
    Compérat, Eva
    Cowan, Nigel C.
    De Santis, Maria
    Gakis, Georgios
    Lebret, Thierry
    Ribal, Maria J.
    Van der Heijden, Antoine G.
    Sherif, Amir
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2013 Guidelines2014Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 65, nr 4, s. 778-792Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONTEXT: The European Association of Urology (EAU) guidelines panel on Muscle-invasive and Metastatic bladder cancer (BCa) updates its guidelines yearly. This updated summary provides a synthesis of the 2013 guidelines document, with emphasis on the latest developments.

    OBJECTIVE: To provide graded recommendations on the diagnosis and treatment of patients with muscle-invasive BCa (MIBC), linked to a level of evidence.

    EVIDENCE ACQUISITION: For each section of the guidelines, comprehensive literature searches covering the past 10 yr in several databases were conducted, scanned, reviewed, and discussed both within the panel and with external experts. The final results are reflected in the recommendations provided.

    EVIDENCE SYNTHESIS: Smoking and work-related carcinogens remain the most important risk factors for BCa. Computed tomography (CT) and magnetic resonance imaging can be used for staging, although CT is preferred for pulmonary evaluation. Open radical cystectomy with an extended lymph node dissection (LND) remains the treatment of choice for treatment failures in non-MIBC and T2-T4aN0M0 BCa. For well-informed, well-selected, and compliant patients, however, multimodality treatment could be offered as an alternative, especially if cystectomy is not an option. Comorbidity, not age, should be used when deciding on radical cystectomy. Patients should be encouraged to actively participate in the decision-making process, and a continent urinary diversion should be offered to all patients unless there are specific contraindications. For fit patients, cisplatinum-based neoadjuvant chemotherapy should always be discussed, since it improves overall survival. For patients with metastatic disease, cisplatin-containing combination chemotherapy is recommended. For unfit patients, carboplatin combination chemotherapy or single agents can be used.

    CONCLUSIONS: This 2013 EAU Muscle-invasive and Metastatic BCa guidelines updated summary aims to increase the quality of care and outcome for patients with muscle-invasive or metastatic BCa.

    PATIENT SUMMARY: In this paper we update the EAU guidelines on Muscle-invasive and Metastatic bladder cancer. We recommend that chemotherapy be administered before radical treatment and that bladder removal be the standard of care for disease confined to the bladder.

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