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Holmberg, Lars
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Publications (10 of 240) Show all publications
Wennstig, A.-K., Wadsten, C., Garmo, H., Fredriksson, I., Blomqvist, C., Holmberg, L., . . . Sund, M. (2020). Long-term risk of ischemic heart disease after adjuvant radiotherapy in breast cancer: results from a large population-based cohort. Breast Cancer Research, 22, Article ID 10.
Open this publication in new window or tab >>Long-term risk of ischemic heart disease after adjuvant radiotherapy in breast cancer: results from a large population-based cohort
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2020 (English)In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 22, article id 10Article in journal (Refereed) Published
Abstract [en]

Background: Adjuvant radiotherapy (RT) for breast cancer (BC) has been associated with an increased risk of ischemic heart disease (IHD). We examined the incidence of IHD in a large population-based cohort of women with BC.

Methods: The Breast Cancer DataBase Sweden (BCBaSe) includes all women diagnosed with BC from 1992 to 2012 (n = 60,217) and age-matched women without a history of BC (n = 300,791) in three Swedish health care regions. Information on comorbidity, educational level, and incidence of IHD was obtained through linkage with population-based registries. The risk of IHD was estimated by Cox proportional hazard regression analyses and cumulative incidence by the Kaplan-Meier method.

Results: Women with BC had a lower risk of IHD compared to women without BC with a hazard ratio (HR) of 0.91 (95% CI 0.88-0.95). When women with left-sided BC were compared to right-sided BC, an increased HR for IHD of 1.09 (95% CI 1.01-1.17) was seen. In women receiving RT, a HR of 1.18 (95% CI 1.06-1.31) was seen in left-sided compared to right-sided BC, and the HRs increased with more extensive lymph node involvement and with the addition of systemic therapy. The cumulative IHD incidence was increased in women receiving left-sided RT compared to right-sided RT, starting from the first years after RT and sustained with longer follow-up.

Conclusions: Women given RT for left-sided BC during 1992 to 2012 had an increased risk of IHD compared to women treated for right-sided BC. These women were treated in the era of three-dimensional conformal RT (3DCRT), and the results emphasize the importance of further developing and implementing RT techniques that lower the cardiac doses, without compromising the beneficial effects of RT.

Place, publisher, year, edition, pages
BMC, 2020
Keywords
Breast cancer, Radiotherapy, Survivorship, Ischemic heart disease, Long-term side effects
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-407283 (URN)10.1186/s13058-020-1249-2 (DOI)000513643300002 ()31969169 (PubMedID)
Funder
The Breast Cancer Foundation, 750491
Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-03-25Bibliographically approved
Beckmann, K., Garmo, H., Adolfsson, J., Bosco, C., Johansson, E., Robinson, D., . . . Van Hemelrijck, M. (2019). Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer. European Urology, 75(4), 676-683
Open this publication in new window or tab >>Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer
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2019 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, no 4, p. 676-683Article in journal (Refereed) Published
Abstract [en]

Background: Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.

Objective: To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.

Design, setting, and participants: Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT).

Outcome measures and statistical methods: Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.

Results and limitations: Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20-144).

Conclusions: Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment.

Patient summary: Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2019
Keywords
Androgen deprivation therapy, Antiandrogen monotherapy, Comorbidity, Gonadotropin-releasing hormone agonists, Prostate cancer
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-380435 (URN)10.1016/j.eururo.2018.11.022 (DOI)000461049200041 ()30497883 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2019-04-09Bibliographically 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
Plym, A., Johansson, A. L. ., Bower, H., Voss, M., Holmberg, L., Fredriksson, I. & Lambe, M. (2019). Causes of sick leave, disability pension, and death following a breast cancer diagnosis in women of working age. Breast, 45, 48-55
Open this publication in new window or tab >>Causes of sick leave, disability pension, and death following a breast cancer diagnosis in women of working age
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2019 (English)In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 45, p. 48-55Article in journal (Refereed) Published
Abstract [en]

Objectives: Women diagnosed with breast cancer during working age are at increased risk of permanent absence from work, but the underlying medical causes have rarely been studied. We examined the risk of cause-specific sick leave, disability pension, and the competing event death after a breast cancer diagnosis in a population-based cohort study.

Materials and methods: From the Breast Cancer Data Base Sweden, we identified 16,603 women diagnosed with stage I-III breast cancer between 2000 and 2012, and 63,773 control women. Using multi-state modelling, we calculated probabilities and durations of sick leave, disability pension, and death by registered cause, together with cause-specific hazard ratios.

Results: Five years after diagnosis, causes other than cancer accounted for around half of all sick leave (3.5% out of 6.8% of women) and disability pension (1.4% out of 2.6%) in women with breast cancer. Compared with control women, women with breast cancer were at increased risk of sick leave and disability pension due to mental disorders (HR 1.24, 95% CI 1.15-1.33 and HR 1.54, 95% CI 1.29-1.85, respectively) and disability pension due to inflammatory diseases (HR 1.46, 95% CI 1.05-2.03). The risk of sick leave and disability pension due to cardiovascular disease was also elevated, although only statistically significant for disability pension in women diagnosed after 2005 (HR 2.24, 95% CI 1.22-4.13).

Conclusion: Follow-up, support, and rehabilitation programs for women diagnosed with breast cancer must address a wide range of psychological and physical conditions to limit the consequences on working life.

Place, publisher, year, edition, pages
CHURCHILL LIVINGSTONE, 2019
Keywords
Breast cancer, Cause of death, Disability pension, Employment, Mental disorders, Sick leave
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-383143 (URN)10.1016/j.breast.2019.02.012 (DOI)000465411900008 ()30852409 (PubMedID)
Funder
Swedish Cancer Society, 14-0324The Breast Cancer Foundation
Available from: 2019-05-13 Created: 2019-05-13 Last updated: 2019-05-13Bibliographically approved
Beckmann, K., Russell, B., Josephs, D., Garmo, H., Häggström, C., Holmberg, L., . . . Adolfsson, J. (2019). Chronic inflammatory diseases, anti-inflammatory medications and risk of prostate cancer: a population-based case-control study. BMC Cancer, 19, Article ID 612.
Open this publication in new window or tab >>Chronic inflammatory diseases, anti-inflammatory medications and risk of prostate cancer: a population-based case-control study
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2019 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, article id 612Article in journal (Refereed) Published
Abstract [en]

Background: Whether chronic inflammation increases prostate cancer risk remains unclear. This study investigated whether chronic inflammatory diseases (CID) or anti-inflammatory medication use (AIM) were associated with prostate cancer risk.

Methods: Fifty-five thousand nine hundred thirty-seven cases (all prostate cancer, 2007-2012) and 279,618 age-matched controls were selected from the Prostate Cancer Database Sweden. CIDs and AIMs was determined from national patient and drug registers. Associations were investigated using conditional logistic regression, including for disease/drug subtypes and exposure length/dose.

Results: Men with a history of any CID had slightly increased risk of any prostate cancer diagnosis (OR: 1.08; 95%CI: 1.04-1.12) but not unfavourable' (high-risk or advanced) prostate cancer. Generally, risk of prostate cancer was highest for shorter exposure times. However, a positive association was observed for asthma >5years before prostate cancer diagnosis (OR: 1.21; 95%CI: 1.05-1.40). Risk of prostate cancer was increased with prior use of any AIMs (OR: 1.26; 95%CI: 1.24-1.29). A positive trend with increasing cumulative dose was only observed for inhaled glucocorticoids (p<0.011).

Conclusion: Detection bias most likely explains the elevated risk of prostate cancer with prior history of CIDs or use of AIMs, given the higher risk immediately after first CID event and lack of dose response. However, findings for length of time with asthma and dose of inhaled glucocorticoids suggest that asthma may increase risk of prostate cancer through other pathways.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Prostate cancer, Chronic inflammatory disease, Autoimmune disease, Anti-inflammatory medication
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-390092 (URN)10.1186/s12885-019-5846-3 (DOI)000472477600005 ()31226970 (PubMedID)
Funder
Swedish Cancer Society, 2013/472
Available from: 2019-08-05 Created: 2019-08-05 Last updated: 2019-12-12Bibliographically approved
Bergengren, O., Garmo, H., Bratt, O., Holmberg, L., Johansson, E. & Bill-Axelson, A. (2019). Determinants for choosing and adhering to active surveillance for localised prostate cancer: a nationwide population-based study. BMJ Open, 9(12), Article ID e033944.
Open this publication in new window or tab >>Determinants for choosing and adhering to active surveillance for localised prostate cancer: a nationwide population-based study
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2019 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, no 12, article id e033944Article in journal (Refereed) Published
Abstract [en]

Objective: Knowledge about factors influencing choice of and adherence to active surveillance (AS) for prostate cancer (PC) is scarce. We aim to identify which factors most affected choosing and adhering to AS and to quantify their relative importance.

Design, setting and participants; In 2015, we sent a questionnaire to all Swedish men aged <= 70 years registered in the National Prostate Cancer Register of Sweden who were diagnosed in 2008 with low-risk PC and had undergone prostatectomy, radiotherapy or started on AS.

Outcome measurements and statistical analysis: Logistic regression was used to calculate ORs with 95% CIs for factors potentially affecting choice and adherence to AS.

Results: 1288 out of 1720 men (75%) responded, 451 (35%) chose AS and 837 (65%) underwent curative treatment. Of those starting on AS, 238 (53%) diverted to treatment within 7 years. Most men (83%) choose AS because 'My doctor recommended AS'. Factors associated with choosing AS over treatment were older age (OR 1.81, 95% CI 1.29 to 2.54), a Charlson Comorbidity Index >2 (OR 1.50, 95% CI 1.06 to 2.13), being unaccompanied when notified of the cancer diagnosis (OR 1.45, 95% CI 1.11 to 1.89). Men with a higher prostate-specific antigen (PSA) at the time of diagnosis were less likely to adhere to AS (OR 0.26, 95% CI 0.10 to 0.63). The reason for having treatment after initial AS was 'the PSA level was rising' in 55% and biopsy findings in 36%.

Conclusions: A doctors recommendation strongly affects which treatment is chosen for men with low-risk PC. Rising PSA values were the main factor for initiating treatment for men on AS. These findings need be considered by healthcare providers who wish to increase the uptake of and adherence to AS.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2019
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-407279 (URN)10.1136/bmjopen-2019-033944 (DOI)000512773400283 ()31874896 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2020-03-23 Created: 2020-03-23 Last updated: 2020-03-23Bibliographically approved
Jahnson, S., Gårdmark, T., Hosseini, A., Jedström, T., Liedberg, F., Malmström, P.-U., . . . Aljabery, F. (2019). Management and outcome of TaG3 tumours of the urinary bladder in the nationwide, population-based bladder cancer database Sweden (BladderBaSe). Scandinavian journal of urology, 53(4), 200-205
Open this publication in new window or tab >>Management and outcome of TaG3 tumours of the urinary bladder in the nationwide, population-based bladder cancer database Sweden (BladderBaSe)
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2019 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 4, p. 200-205Article in journal (Refereed) Published
Abstract [en]

Purpose: To investigate the management of TaG3 tumours of the urinary bladder using nationwide population-based data in relation to the prevailing guidelines, patients' characteristics, and outcome. Materials and methods: The Bladder Cancer Data Base Sweden (BladderBaSe), including data from the Swedish National Register for Urinary Bladder Cancer (SNRUBC), was used to study all patients with TaG3 bladder cancer diagnosed from 2008 to 2014. Patients were divided into the following management groups: (1) transurethral resection (TUR) only, (2) TUR and intravesical instillation therapy (IVIT), (3) TUR and second-look resection (SLR), and (4) TUR with both SLR and IVIT. Patient and tumour characteristics and outcome were studied. Results: There were 831 patients (83% males) with a median age of 74 years. SLR was performed more often on younger patients, on men, and less often in the Western and Uppsala/orebro Healthcare regions. IVIT was performed more often with younger patients, with men, in the Western Healthcare region, and less often in the Uppsala/orebro Healthcare region. Death from bladder cancer occurred in 6% of cases within a median of 29 months (0-84 months) and was lower in the TUR/IVIT and TUR/SLR/IVIT groups compared to the other two groups. Conclusion: In the present study, there was, according to the prevailing treatment guidelines, an under-treatment with SLR for older patients, women, and in some healthcare regions and, similarly, there was an under-treatment with IVIT for older patients. Cancer-specific survival and relative survival were lower in the TUR only group compared to the TUR/IVIT and TUR/SLR/IVIT groups.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2019
Keywords
Bladder cancer, population-based, TaG3, second-look resection, intravesical instillation treatment
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-398723 (URN)10.1080/21681805.2019.1621377 (DOI)000471561600001 ()31144582 (PubMedID)
Funder
Swedish Cancer Society, CAN 2016/470Swedish Cancer Society, CAN 278
Available from: 2019-12-10 Created: 2019-12-10 Last updated: 2019-12-12Bibliographically 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
Ahlberg, M. S., Adami, H.-O., Beckmann, K., Bertilsson, H., Bratt, O., Cahill, D., . . . Bill-Axelson, A. (2019). PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer: rationale and design. BMJ Open, 9(8)
Open this publication in new window or tab >>PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer: rationale and design
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2019 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, no 8Article in journal (Refereed) Published
Abstract [en]

Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, <= T2a, prostate-specific antigen (PSA) <15ng/mL, PSA density <less than or equal to>0.2ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled. Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2019
Keywords
active surveillance, MRI, prostate cancer, randomised trial
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-401175 (URN)10.1136/bmjopen-2018-027860 (DOI)000502537200134 ()31444180 (PubMedID)
Funder
Swedish Cancer Society, 2016/466Swedish Cancer Society, 2014/1275Swedish Research Council, 2016-00177Swedish Research Council, 2016-01293
Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-01-07Bibliographically approved
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