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Robinson, D., Garmo, H., Van Hemelrijck, M., Damber, J.-E., Bratt, O., Holmberg, L., . . . Adolfsson, J. (2019). Androgen deprivation therapy for prostate cancer and risk of dementia. BJU International, 124(1), 87-92
Open this publication in new window or tab >>Androgen deprivation therapy for prostate cancer and risk of dementia
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2019 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 124, no 1, p. 87-92Article in journal (Refereed) Published
Abstract [en]

Objectives

To study whether androgen deprivation therapy (ADT), the mainstay treatment for advanced and disseminated prostate cancer, is associated with risk of dementia.

Methods

Risk of dementia in men with prostate cancer primarily managed with ADT or watchful waiting (WW) in the Prostate Cancer Database Sweden, PCBaSe, was compared with that in prostate cancer-free men, matched on birth year and county of residency. We used Cox regression to calculate the hazard ratios (HRs) for Alzheimer's and non-Alzheimer's dementia (vascular dementia, dementia secondary to other diseases or unspecified dementias) for different types and duration of ADT and oral antiandrogens (AAs) as well as for men managed with WW.

Results

A total of 25 967 men with prostate cancer and 121 018 prostate cancer-free men were followed for a median of 4 years. In both groups 6% of the men were diagnosed with dementia. In men with prostate cancer, gonadotropin-releasing hormone agonist treatment ( HR 1.15, 95% confidence interval [CI] 1.07-1.23) and orchiectomy (HR 1.60, 95% CI 1.32-1.93) were associated with an increased risk of dementia, as compared to no treatment in prostate cancer-free men; however, this increase in risk was only observed for non-Alzheimer's dementia and occurred from year 1-4 after start of ADT. No increase in risk for any type of dementia was observed for men treated with AAs or for men on WW.

Conclusion

This population-based cohort study does not support previous observations of an increased risk of Alzheimer's dementia for men on ADT; however, there was a small increase in risk of non-Alzheimer's dementia.

Keywords
androgen deprivation therapy, dementia, #ProstateCancer, #PCSM, #ADT, #Dementia
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-388761 (URN)10.1111/bju.14666 (DOI)000471830900016 ()30637900 (PubMedID)
Funder
Swedish Research Council, 825-2012-5047Swedish Cancer Society, 16-0700Swedish Cancer Society, 16-286Swedish Cancer Society, 16-464
Available from: 2019-08-13 Created: 2019-08-13 Last updated: 2019-08-14Bibliographically approved
Thomsen, F. B., Bosco, C., Garmo, H., Adolfsson, J., Hammar, N., Stattin, P. & Van Hemelrijck, M. (2019). Anti-androgen monotherapy versus gonadotropin-releasing hormone agonists in men with advanced, non-metastatic prostate cancer: a register-based, observational study. Acta Oncologica, 58(1), 110-118
Open this publication in new window or tab >>Anti-androgen monotherapy versus gonadotropin-releasing hormone agonists in men with advanced, non-metastatic prostate cancer: a register-based, observational study
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2019 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 1, p. 110-118Article in journal (Refereed) Published
Abstract [en]

Background:

In randomised controlled trials, men with advanced, non-metastatic prostate cancer (PCa) treated with anti-androgen monotherapy (AA) had similar all-cause mortality as men treated with gonadotropin-releasing hormone (GnRH) agonists. Using real-world evidence (i.e., observational data), we aimed to further assess the difference in mortality between these two drug categories.

Material and Methods:

We emulated a trial using data from Prostate Cancer data Base Sweden 3.0. We specifically focused on men diagnosed in 2006-2012 with high-risk PCa who had no distant metastasis. They either received primary hormonal therapy with AA (n=2078) or GnRH agonists (n=4878) who were followed for a median time of 5 years. Risk of death from PCa and other causes was assessed using competing risk analyses and Cox proportional hazards regression analyses, including propensity score matching.

Results:

The cumulative 5-year PCa mortality was lower for men treated with AA (16% [95% confidence interval, CI, 15-18%]) than men treated with GnRH agonists (22% [95% CI 21-24%]). The 5-year other cause mortality was also lower for men on AA (17% [95% CI 15-19%] compared to men on GnRH agonists (27% [95% CI 25-28%]). In regression analyses, the risk of PCa death was similar, GnRH agonists versus AA (reference), hazard ratio (HR) 1.08 (95% CI 0.95-1.23), but the risk of death from all causes was higher for men on GnRH agonists, HR 1.23 (95% CI 1.13-1.34). Consistent results were seen in the propensity score-matched cohort.

Conclusion:

Our results indicate that the use of AA as primary hormonal therapy in men with high-risk non-metastatic PCa does not increase PCa-specific mortality compared to GnRH. Using AA instead of GnRH agonists may result in shorter time on/exposure to GnRH-treatment, which may reduce the risk of adverse events associated with this treatment.

National Category
Cancer and Oncology Urology and Nephrology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-379242 (URN)10.1080/0284186X.2018.1529427 (DOI)000459620200015 ()30375907 (PubMedID)
Funder
Swedish Research Council, 825-2012-5047
Available from: 2019-03-19 Created: 2019-03-19 Last updated: 2019-03-19Bibliographically approved
Essen, A., Santaolalla, A., Garmo, H., Hammar, N., Walldius, G., Jungner, I., . . . Van Hemelrijck, M. (2019). Baseline serum folate, vitamin B12 and the risk of prostate and breast cancer using data from the Swedish AMORIS cohort. Cancer Causes and Control, 30(6), 603-615
Open this publication in new window or tab >>Baseline serum folate, vitamin B12 and the risk of prostate and breast cancer using data from the Swedish AMORIS cohort
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2019 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 30, no 6, p. 603-615Article in journal (Refereed) Published
Abstract [en]

Purpose: The roles of folate and vitamin B12 in prostate cancer (PCa) or breast cancer (BC) development are unclear. We investigated their roles using the prospective Swedish Apolipoprotein MOrtality RISk (AMORIS) study.

Methods: 8,783 men and 19,775 women with vitamin B12 and folate serum measurements were included. Their associations with PCa and BC risk categories were evaluated using Cox proportional hazards regression.

Results: During mean follow-up of 13years, 703 men developed PCa. There was an inverse association between folate>32nmol/L and high-risk PCa [hazard ratio (HR) 0.12, 95% confidence interval (CI) 0.02-0.90], and a positive association between folate<5nmol/L and metastatic PCa (HR 5.25, 95% CI 1.29-21.41), compared with folate 5-32nmol/L. No associations with vitamin B12 were found. 795 women developed BC during mean follow-up of 14years. When restricting to the fasting population, there was a positive association between folate>32nmol/L and BC (HR 1.47, 95% CI 1.06-2.04).

Conclusion: High folate levels may protect against PCa and low folate levels may increase risk of metastatic PCa. High fasting folate levels may be associated with an increased BC risk. Vitamin B12 was not found to be linked with risk of PCa or BC. Longitudinal studies with serum and dietary information could help define new prevention targets and add information on the role of folate fortification.

Place, publisher, year, edition, pages
SPRINGER, 2019
Keywords
Prostate cancer (PCa), Breast cancer (BC), Vitamin B12, Folate, Severity
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-384996 (URN)10.1007/s10552-019-01170-6 (DOI)000467796500005 ()31020446 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-06-11 Created: 2019-06-11 Last updated: 2019-06-11Bibliographically approved
Ventimiglia, E., Van Hemelrijck, M., Lindhagen, L., Stattin, P. & Garmo, H. (2019). How to measure temporal changes in care pathways for chronic diseases using health care registry data. BMC Medical Informatics and Decision Making, 19, Article ID 103.
Open this publication in new window or tab >>How to measure temporal changes in care pathways for chronic diseases using health care registry data
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2019 (English)In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 19, article id 103Article in journal (Refereed) Published
Abstract [en]

Background: Disease trajectories for chronic diseases can span over several decades, with several time-dependent factors affecting treatment decisions. Thus, there is a need for long-term predictions of disease trajectories to inform patients and healthcare professionals on the long-term outcomes and provide information on the need of future health care. Here, we propose a state transition model to describe and predict disease trajectories up to 25 years after diagnosis in men with prostate cancer (PCa), as a proof of principle. Methods: States, state transitions, and transition probabilities were identified and estimated in Prostate Cancer data Base of Sweden (PCBaSeTraject), using nationwide population-based data from 118,743 men diagnosed with PCa. A state transition model in discrete time steps (i.e., 4 weeks) was developed and applied to capture all possible transitions (PCBaSeSim). Transition probabilities were estimated for changes in both treatment and comorbidity. These models combined yielded parameter estimates to run an individual-level simulation based on the state-transition model to obtain prediction estimates. Predicted estimates were then compared to real world data in PCBaSeTraject. Results: PCBaSeSim estimates for the cumulative incidence of first and second transitions, death from PCa and death from other causes were compared to observed transitions in PCBaSeTraject. A good agreement was found between simulated and observed estimates. Conclusions: We developed a reliable and accurate simulation tool, PCBaSeSim that provides information on disease trajectories for subjects with a chronic disease on an individual and population-based level.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Ageing, Chronic disease, Prostate cancer, State transition
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-386444 (URN)10.1186/s12911-019-0823-y (DOI)000469777500001 ()31146754 (PubMedID)
Funder
Swedish Research Council, 825-2008-5910Forte, Swedish Research Council for Health, Working Life and WelfareVästerbotten County CouncilThe Cancer Society in Stockholm
Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2019-06-26Bibliographically approved
Cazzaniga, W., Garmo, H., Robinson, D., Holmberg, L., Bill-Axelson, A. & Stattin, P. (2019). Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study. BJU International, 123(3), 421-428
Open this publication in new window or tab >>Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study
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2019 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 123, no 3, p. 421-428Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision-making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG-4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s.

PATIENTS AND METHODS: A propensity score-matched analysis of prostate cancer mortality and all-cause mortality in the SPCG-4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998-2006 was conducted. Cumulative incidence of prostate cancer mortality and all-cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR.

RESULTS: Matched men in the NPCR treated in 2005-2006 had half the risk of prostate cancer mortality compared to men in the SPCG-4 (HR 0.46, 95% CI 0.19-1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36-1.47).

CONCLUSIONS: Outcomes after RP for men in the SPCG-4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG-4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.

Keywords
Gleason Grade Groups, mortality, National Prostate Cancer Register of Sweden, Scandinavian Prostate Cancer Group Study Number 4, #PCSM, #ProstateCancer
National Category
Medical and Health Sciences Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-381179 (URN)10.1111/bju.14563 (DOI)000460173100013 ()30253031 (PubMedID)
Funder
Swedish Research Council, 2017-00847
Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-04-12Bibliographically approved
Hailer, N. P., Garland, A., Gordon, M., Karrholm, J., Skoldenberg, O., Eriksson, N., . . . Holmberg, L. (2019). No generally increased risk of cancer after total hip arthroplasty performed due to osteoarthritis. International Journal of Cancer
Open this publication in new window or tab >>No generally increased risk of cancer after total hip arthroplasty performed due to osteoarthritis
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Article in journal (Refereed) Epub ahead of print
Abstract [en]

Previous studies on the risk of cancer after total hip arthroplasty (THA) contradict each other, and many are hampered by small cohort sizes, residual confounding, short observation times or a mix of indications underlying the THA procedure. We evaluated the risk of cancer after total hip arthroplasty due to osteoarthritis in a nationwide cohort by comparing cancer incidences in individuals exposed to total hip arthroplasty due to osteoarthritis and in unexposed, sex-, age- and residence matched individuals. To address some previous studies' shortcomings, information on comorbidity and socioeconomic background were obtained and adjusted for. We included 126,276 patients exposed to a cemented THA between 1992 and 2012, and 555,757 unexposed individuals. Follow-up started on the day of surgery for exposed individuals and respective date for matched, unexposed individuals, and ended on the day of death, emigration, censuring or December 31st, 2012, whichever came first. The Swedish Hip Arthroplasty Registry (SHAR), the Swedish Cancer Registry, the Swedish National Patient Registry and Statistics Sweden were accessed to obtain information on procedural details of the THA, cancer diagnoses, comorbidities, and socioeconomic background. The primary outcome measure was the occurrence of any cancer after the index date. Exposed individuals had a slightly lower adjusted risk of developing any cancer than unexposed individuals (hazard ratio [HR] 0.97; CI 0.95-0.99). The only cancer with a statistically significant risk increase in exposed individuals was skin melanoma (HR 1.15; CI 1.05-1.24). We attained similar risk estimates in analyses stratified by sex, in individuals with minimum 5 years of follow-up, in an analysis including individuals with a history of previous cancer, and in patients with cementless THA. In this study on a large and well-defined population with long follow-up, we found no increased overall risk of cancer after THA. These reassuring findings could be included in the guidelines on preoperative information given to THA patients.

Keywords
total hip replacement, total hip arthroplasty, cancer, nationwide, Sweden
National Category
Cancer and Oncology Orthopaedics
Identifiers
urn:nbn:se:uu:diva-397670 (URN)10.1002/ijc.32711 (DOI)000494074900001 ()31595487 (PubMedID)
Available from: 2019-11-28 Created: 2019-11-28 Last updated: 2019-11-28Bibliographically approved
Bill-Axelson, A., Holmberg, L. & Garmo, H. (2019). Radical Surgery or Watchful Waiting in Prostate Cancer Reply [Letter to the editor]. New England Journal of Medicine, 380(11), 1084-1084
Open this publication in new window or tab >>Radical Surgery or Watchful Waiting in Prostate Cancer Reply
2019 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 380, no 11, p. 1084-1084Article in journal, Letter (Other academic) Published
National Category
Cancer and Oncology General Practice
Identifiers
urn:nbn:se:uu:diva-380667 (URN)10.1056/NEJMc1900410 (DOI)000461210000019 ()30865809 (PubMedID)
Available from: 2019-04-01 Created: 2019-04-01 Last updated: 2019-04-01Bibliographically approved
Wärnberg, F., Garmo, H., Folkvaljon, Y., Holmberg, L., Karlsson, P., Sandelin, K., . . . Bremer, T. (2018). Abstract GS5-08: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS). Paper presented at San Antonio Breast Cancer Symposium, DEC 05-09, 2017, San Antonio, TX. Cancer Research, 78(4)
Open this publication in new window or tab >>Abstract GS5-08: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS)
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2018 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, no 4Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-351602 (URN)10.1158/1538-7445.SABCS17-GS5-08 (DOI)000425489400036 ()
Conference
San Antonio Breast Cancer Symposium, DEC 05-09, 2017, San Antonio, TX
Note

Wos title: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS)

Supplement: S

Meeting Abstract: GS5-08

Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2018-09-12Bibliographically approved
Wadsten, C., Wärnberg, F., Tolockiene, E., Hartman, J., Fredriksson, I., Garmo, H. & Sund, M. (2018). Biomarkers in DCIS associated with breast cancer death. Paper presented at 11th European Breast Cancer Conference (EBCC), MAR 21-23, 2018, Barcelona, SPAIN. European Journal of Cancer, 92, S67-S68
Open this publication in new window or tab >>Biomarkers in DCIS associated with breast cancer death
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2018 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 92, p. S67-S68Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-357180 (URN)000429103100169 ()
Conference
11th European Breast Cancer Conference (EBCC), MAR 21-23, 2018, Barcelona, SPAIN
Available from: 2018-08-14 Created: 2018-08-14 Last updated: 2018-08-14Bibliographically approved
Ghoshal, A., Garmo, H., Hammar, N., Jungner, I., Malmström, H., Walldius, G. & Van Hemelrijck, M. (2018). Can pre-diagnostic serum levels of sodium and potassium predict prostate cancer survival?. BMC Cancer, 18, Article ID 1169.
Open this publication in new window or tab >>Can pre-diagnostic serum levels of sodium and potassium predict prostate cancer survival?
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2018 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 18, article id 1169Article in journal (Refereed) Published
Abstract [en]

There is evidence that derangement in serum electrolytes like sodium and potassium is associated with increased morbidity and mortality among hospitalized critically ill patients, but their role in the context of cancer survival remains poorly understood. We sought to investigate the association of pre-diagnostic serum sodium and potassium with risk of overall, cancer-specific, and cardiovascular (CV) death among 11,492 men diagnosed with prostate cancer (PCa) from the Swedish AMORIS study. Multivariable Cox proportional hazards regression was used to assess the risk of death by clinical categories of pre-diagnostic serum sodium and potassium. During a mean follow-up of 5.7years, 1649 men died of PCa. Serum levels of sodium were not indicative of PCa-specific or CV death. A weak positive association was found between pre-diagnostic higher serum potassium (>5mEq/L) and overall death [HR: 1.26 (95% CI: 1.01-1.59)] as compared to low/normal levels of clinical cut-offs. The current study did not find strong evidence for a role of electrolytes in PCa mortality. To further disentangle the potential role of electrolytes in cancer development, future studies should use repeated measurement of serum electrolytes. This research project was reviewed and approved by the Stockholm Ethical Committee (Dnr 2010/1:7).

Keywords
AMORIS cohort, Prospective study, Prostate cancer, Serum electrolytes, Survival analysis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-372450 (URN)10.1186/s12885-018-5098-7 (DOI)000451262600008 ()30477464 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-7181-7083

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