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Publications (10 of 38) Show all publications
Wikström, P., Bergh, A., Josefsson, A., Thysell, E. & Welén, K. (2024). Molekylära subtyper och avancerad prostatacancer: nya möjligheter för anpassad behandling: [Molecular subtypes provide possibilities for precision medicine in a advanced prostate cancer]. Läkartidningen, 121, Article ID 23179.
Open this publication in new window or tab >>Molekylära subtyper och avancerad prostatacancer: nya möjligheter för anpassad behandling: [Molecular subtypes provide possibilities for precision medicine in a advanced prostate cancer]
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2024 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 121, article id 23179Article, review/survey (Refereed) Published
Abstract [en]

Increased molecular knowledge makes it possible to consider not only genetic defects but also expression profiles for precision medicine in advanced prostate cancer. Several prognostic and treatment-predictive classifiers for prostate cancer have been described, such as Prolaris, OncotypeDx, Decipher, Prostatype, PAM50, PCS1-2, and MetA-C, which all build upon transcript profiles. In research studies, the MetA-C classifier has shown clear prognostic information for patients with metastatic disease, in relation to outcome after androgen receptor targeting therapies, and so has immunohistochemical evaluation of tumor cell proliferation (Ki67) and PSA expression. Unfortunately, methods within clinical routine today do not allow molecular subclassification of prostate cancer. To enable comparison of the most promising treatment-predictive biomarkers and to evaluate the health economic value of implementing such precision medicine for prostate cancer, a prospective study is being planned as a joint initiative in Sweden that aims to evaluate and validate biomarkers and to establish a study platform for adaptive biomarker-driven clinical trials (sprintr.se).

Place, publisher, year, edition, pages
Läkartidningen Förlag AB, 2024
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-224113 (URN)2-s2.0-85191380918 (Scopus ID)
Available from: 2024-05-13 Created: 2024-05-13 Last updated: 2024-05-13Bibliographically approved
Rajwa, P., Borkowetz, A., Abbott, T., Alberti, A., Bjartell, A., Brash, J. T., . . . Willemse, P.-P. M. (2024). Research protocol for an observational health data analysis on the adverse events of systemic treatment in patients with metastatic hormone-sensitive prostate cancer: big data analytics using the PIONEER platform. European Urology Open Science, 63, 81-88
Open this publication in new window or tab >>Research protocol for an observational health data analysis on the adverse events of systemic treatment in patients with metastatic hormone-sensitive prostate cancer: big data analytics using the PIONEER platform
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2024 (English)In: European Urology Open Science, ISSN 2666-1691, E-ISSN 2666-1683, Vol. 63, p. 81-88Article in journal (Refereed) Published
Abstract [en]

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in “real-life” patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Androgen receptor signaling inhibitor, Big data, Docetaxel, Hormone sensitive, Metastatic, PIONEER, Prostate cancer
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-222894 (URN)10.1016/j.euros.2024.02.019 (DOI)38572301 (PubMedID)2-s2.0-85188780237 (Scopus ID)
Funder
EU, Horizon 2020
Available from: 2024-04-05 Created: 2024-04-05 Last updated: 2024-04-05Bibliographically approved
Josefsson, A., Jellvert, Å., Holmberg, E., Brasso, K., Meidahl Petersen, P., Aaltomaa, S., . . . Damber, J.-E. (2023). Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14). Acta Oncologica, 62(4), 372-380
Open this publication in new window or tab >>Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)
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2023 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 62, no 4, p. 372-380Article in journal (Refereed) Published
Abstract [en]

Background: Historically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS).

Materials and Methods: Patients with hormone-naïve, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m2, q3w, 8–10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis.

Results: Between 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0–5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50–0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49–0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse.

Conclusion: Docetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.

Place, publisher, year, edition, pages
Taylor & Francis, 2023
Keywords
bicalutamide, docetaxel, Prostate cancer, psa relapse, randomized clinical trial
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-207884 (URN)10.1080/0284186X.2023.2199940 (DOI)000971229600001 ()37073813 (PubMedID)2-s2.0-85153790361 (Scopus ID)
Funder
ProstatacancerförbundetRegion Västra Götaland, ALFGBG-428341Region Västra Götaland, ALFGBG-7243Knut and Alice Wallenberg Foundation
Available from: 2023-05-08 Created: 2023-05-08 Last updated: 2024-02-01Bibliographically approved
Ahlin, R., Nørskov, N. P., Nybacka, S., Landberg, R., Skokic, V., Stranne, J., . . . Hedelin, M. (2023). Effects on serum hormone concentrations after a dietary phytoestrogen intervention in patients with prostate cancer: a randomized controlled trial. Nutrients, 15(7), Article ID 1792.
Open this publication in new window or tab >>Effects on serum hormone concentrations after a dietary phytoestrogen intervention in patients with prostate cancer: a randomized controlled trial
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2023 (English)In: Nutrients, E-ISSN 2072-6643, Vol. 15, no 7, article id 1792Article in journal (Refereed) Published
Abstract [en]

Phytoestrogens have been suggested to have an anti-proliferative role in prostate cancer, potentially by acting through estrogen receptor beta (ERβ) and modulating several hormones. We primarily aimed to investigate the effect of a phytoestrogen intervention on hormone concentrations in blood depending on the ERβ genotype. Patients with low and intermediate-risk prostate cancer, scheduled for radical prostatectomy, were randomized to an intervention group provided with soybeans and flaxseeds (∼200 mg phytoestrogens/d) added to their diet until their surgery, or a control group that was not provided with any food items. Both groups received official dietary recommendations. Blood samples were collected at baseline and endpoint and blood concentrations of different hormones and phytoestrogens were analyzed. The phytoestrogen-rich diet did not affect serum concentrations of testosterone, insulin-like growth factor 1, or sex hormone-binding globulin (SHBG). However, we found a trend of decreased risk of increased serum concentration of estradiol in the intervention group compared to the control group but only in a specific genotype of ERβ (p = 0.058). In conclusion, a high daily intake of phytoestrogen-rich foods has no major effect on hormone concentrations but may lower the concentration of estradiol in patients with prostate cancer with a specific genetic upset of ERβ.

Place, publisher, year, edition, pages
MDPI, 2023
Keywords
estradiol, insulin-like growth factor 1, isoflavones, lignans, phytoestrogens, prostate cancer, sex hormone-binding globulin, testosterone
National Category
Nutrition and Dietetics Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-207703 (URN)10.3390/nu15071792 (DOI)000969674300001 ()2-s2.0-85152777258 (Scopus ID)
Funder
King Gustaf V Jubilee Fund, 2021:353King Gustaf V Jubilee Fund, 2020:320King Gustaf V Jubilee Fund, 2019:262King Gustaf V Jubilee Fund, 2018:206King Gustaf V Jubilee Fund, 2017:145King Gustaf V Jubilee Fund, 2016:76Dr P Håkanssons stiftelseKnut and Alice Wallenberg Foundation, 2015.0114
Available from: 2023-04-28 Created: 2023-04-28 Last updated: 2024-02-01Bibliographically approved
Spyratou, V., Freyhult, E., Bergh, A., Thellenberg-Karlsson, C., Wikström, P., Welén, K. & Josefsson, A. (2023). Ki67 and prostate specific antigen are prognostic in metastatic hormone naïve prostate cancer. Acta Oncologica, 6212, 1698-1706
Open this publication in new window or tab >>Ki67 and prostate specific antigen are prognostic in metastatic hormone naïve prostate cancer
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2023 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 6212, p. 1698-1706Article in journal (Refereed) Published
Abstract [en]

Background: For metastatic hormone naïve prostate cancer patients, androgen deprivation therapy (ADT) with escalation therapy including docetaxel and/or androgen targeting drugs is the standard therapy. However, de-escalation is preferable to avoid unnecessary side effects, especially from docetaxel, but markers to identify these patients are lacking. The purpose of the present study was to investigate the potential of PSA and Ki67 immunoreactive scores as prognostic and treatment-predictive markers.

Material and methods: Prostate biopsies from 92 patients with metastatic hormone naïve PC (PSA > 80 ng/mL or clinical metastases) were immunohistochemically evaluated for PSA and Ki67. Gene expression analysis was performed with Clariom D microarrays to identify the phenotypic profile associated with the immunohistochemistry scores of biopsies. Cox regression analysis for progression free survival after ADT adjustment for age, ISUP, and serum PSA and Kaplan-Meier analyses were performed to assess prognostic values of Ki67, PSA, and the Ki67/PSA ratio.

Results: The immunohistochemical score for PSA was the strongest prognostic factor for progression-free and overall survival after ADT. Consequently, the ratio between Ki67 and PSA displayed a stronger prognostic value than Ki67 itself. Further, mRNA expression data analysis showed an association between high Ki67/PSA ratio, cell-cycle regulation, and DNA damage repair. In an exploratory sub-analysis of 12 patients treated with early docetaxel as addition to ADT and matched controls, a high Ki67/PSA ratio showed potential to identify those who benefit from docetaxel.

Conclusion: PSA and Ki67 immunoreactive scores are prognostic in the metastatic hormone-sensitive setting, with PSA being superior. The combination of Ki67 and PSA did not give additional prognostic value. The results suggest immunohistochemical scoring of PSA to have potential to improve identification of patients responding well to ADT alone.

Place, publisher, year, edition, pages
Taylor & Francis, 2023
Keywords
androgen deprivation therapy, biomarker, docetaxel, Metastatic prostate cancer, prostate specific antigen
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-214585 (URN)10.1080/0284186X.2023.2254480 (DOI)001068664400001 ()37713321 (PubMedID)2-s2.0-85171153075 (Scopus ID)
Funder
Swedish Research Council, 2022-00946Swedish Cancer Society, 19-0054Swedish Cancer Society, 19-0053Swedish Cancer Society, 20-1055Swedish Cancer Society, 21-1856Knut and Alice Wallenberg Foundation, 2020.0235Prostatacancerförbundet
Available from: 2023-09-28 Created: 2023-09-28 Last updated: 2024-02-01Bibliographically approved
Welén, K., Rosendal, E., Gisslén, M., Lenman, A., Freyhult, E., Fonseca Rodriguez, O., . . . Josefsson, A. (2022). A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data. European Urology, 81(3), 285-293
Open this publication in new window or tab >>A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
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2022 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 81, no 3, p. 285-293Article in journal (Refereed) Published
Abstract [en]

Background: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.

Objective: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection.

Designs, settings, and participants: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells.

Intervention: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care.

Outcome measurements: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition.

Results and limitations: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders.

Conclusions: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted.

Patient summary: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
COVID-19, SARS-CoV-2, Antiandrogen, Randomized trial, Enzalutamide, Bicalutamide, Androgen deprivation therapy
National Category
Cancer and Oncology Public Health, Global Health, Social Medicine and Epidemiology Urology and Nephrology Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-190911 (URN)10.1016/j.eururo.2021.12.013 (DOI)000809752100020 ()2-s2.0-85122412349 (Scopus ID)
Funder
Knut and Alice Wallenberg Foundation, 2020.0182ProstatacancerförbundetSwedish Cancer Society, 2017/478Swedish Cancer Society, 20 1055 PjFSwedish Heart Lung Foundation, 20200385Region Västerbotten, RV-836351Region Västerbotten, RV-939769
Available from: 2022-01-02 Created: 2022-01-02 Last updated: 2023-04-25Bibliographically approved
Sund, M., Fonseca-Rodríguez, O., Josefsson, A., Welen, K. & Fors Connolly, A.-M. (2022). Association between pharmaceutical modulation of oestrogen in postmenopausal women in Sweden and death due to COVID-19: a cohort study. BMJ Open, 12(2), Article ID e053032.
Open this publication in new window or tab >>Association between pharmaceutical modulation of oestrogen in postmenopausal women in Sweden and death due to COVID-19: a cohort study
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2022 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 2, article id e053032Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Determine whether augmentation of oestrogen in postmenopausal women decreases the risk of death following COVID-19.

DESIGN: Nationwide registry-based study in Sweden based on registries from the Swedish Public Health Agency (all individuals who tested positive for SARS-CoV-2); Statistics Sweden (socioeconomical variables) and the National Board of Health and Welfare (causes of death).

PARTICIPANTS: Postmenopausal women between 50 and 80 years of age with verified COVID-19.

INTERVENTIONS: Pharmaceutical modulation of oestrogen as defined by (1) women with previously diagnosed breast cancer and receiving endocrine therapy (decreased systemic oestrogen levels); (2) women receiving hormone replacement therapy (increased systemic oestrogen levels) and (3) a control group not fulfilling requirements for group 1 or 2 (postmenopausal oestrogen levels). Adjustments were made for potential confounders such as age, annual disposable income (richest group as the reference category), highest level of education (primary, secondary and tertiary (reference)) and the weighted Charlson Comorbidity Index (wCCI). PRIMARY OUTCOME MEASURE: Death following COVID-19.

RESULTS: From a nationwide cohort consisting of 49 853 women diagnosed with COVID-19 between 4 February and 14 September 2020 in Sweden, 16 693 were between 50 and 80 years of age. We included 14 685 women in the study with 11 923 (81%) in the control group, 227 (2%) women in group 1 and 2535 (17%) women in group 2. The unadjusted ORs for death following COVID-19 were 2.35 (95% CI 1.51 to 3.65) for group 1 and 0.45 (0.34 to 0.6) for group 2. Only the adjusted OR for death remained significant for group 2 with OR 0.47 (0.34 to 0.63). Absolute risk of death was 4.6% for the control group vs 10.1% and 2.1%, for the decreased and increased oestrogen groups, respectively. The risk of death due to COVID-19 was significantly associated with: age, OR 1.15 (1.14 to 1.17); annual income, poorest 2.79 (1.96 to 3.97), poor 2.43 (91.71 to 3.46) and middle 1.64 (1.11 to 2.41); and education (primary 1.4 (1.07 to 1.81)) and wCCI 1.13 (1.1 to 1.16).

CONCLUSIONS: Oestrogen supplementation in postmenopausal women is associated with a decreased risk of dying from COVID-19 in this nationwide cohort study. These findings are limited by the retrospective and non-randomised design. Further randomised intervention trials are warranted.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2022
Keywords
COVID-19, epidemiology, sex steroids & HRT
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-192740 (URN)10.1136/bmjopen-2021-053032 (DOI)000755179700010 ()35165090 (PubMedID)2-s2.0-85124680027 (Scopus ID)
Funder
Region Västerbotten, RV-836351Knut and Alice Wallenberg Foundation
Available from: 2022-02-24 Created: 2022-02-24 Last updated: 2023-09-05Bibliographically approved
Thysell, E., Köhn, L., Semenas, J., Järemo, H., Freyhult, E., Lundholm, M., . . . Wikström, P. (2022). Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C. Molecular Oncology (4)
Open this publication in new window or tab >>Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C
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2022 (English)In: Molecular Oncology, ISSN 1574-7891, E-ISSN 1878-0261, no 4Article in journal (Refereed) Published
Abstract [en]

To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes, and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n=17), short-term castrated (n=21) or castration resistant (n=65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples was also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single-nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen-receptor-targeting treatments.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
MetA-C, Metastasis, Prognosis, Prostate cancer, Subtypes, Transcriptomic
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-190463 (URN)10.1002/1878-0261.13158 (DOI)000734478400001 ()34889043 (PubMedID)2-s2.0-85121666619 (Scopus ID)
Available from: 2021-12-16 Created: 2021-12-16 Last updated: 2023-10-23Bibliographically approved
Wikström, P., Halin Bergström, S., Josefsson, A., Semenas, J., Nordstrand, A., Thysell, E., . . . Bergh, A. (2022). Epithelial and stromal characteristics of primary tumors predict the bone metastatic subtype of prostate cancer and patient survival after androgen-deprivation therapy. Cancers, 14(21), Article ID 5195.
Open this publication in new window or tab >>Epithelial and stromal characteristics of primary tumors predict the bone metastatic subtype of prostate cancer and patient survival after androgen-deprivation therapy
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2022 (English)In: Cancers, ISSN 2072-6694, Vol. 14, no 21, article id 5195Article in journal (Refereed) Published
Abstract [en]

Prostate cancer (PC) bone metastases can be divided into transcriptomic subtypes, by us termed MetA-C. The MetB subtype, constituting about 20% of the cases, is characterized by high cell cycle activity, low androgen receptor (AR) activity, and a limited response to standard androgen deprivation therapy (ADT). Complementary treatments should preferably be introduced early on if the risk of developing metastases of the MetB subtype is predicted to behigh. In this study, we therefore examined if the bone metastatic subtype and patient outcome after ADT could be predicted by immunohistochemical analysis of epithelial and stromal cell markers in primary tumor biopsies obtained at diagnosis (n = 98). In this advanced patient group, primary tumor International Society of Urological Pathology (ISUP) grade was not associated with outcome or metastasis subtype. In contrast, high tumor cell Ki67 labeling (proliferation) in combination with low tumor cell immunoreactivity for PSA, and a low fraction of AR positive stroma cells in the primary tumors were prognostic for poor survival after ADT. Accordingly, the same tissue markers were associated with developing metastases enriched for the aggressive MetB subtype. The development of the contrasting MetA subtype, showing the best response to ADT, could be predicted by the opposite staining pattern. We conclude that outcome after ADT and metastasis subtype can, at least to some extent, be predicted by analysis of primary tumor characteristics, such as tumor cell proliferation and PSA expression, and AR expression in stromal cells.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
androgen receptor, bone metastases, ERG, Ki67, metastatic subtypes, PDGFRB, prostate cancer, PSA, SDF1, smooth muscle actin
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-201227 (URN)10.3390/cancers14215195 (DOI)000880962300001 ()36358614 (PubMedID)2-s2.0-85141664487 (Scopus ID)
Funder
Swedish Foundation for Strategic Research, RB13-0119Swedish Cancer Society, 19 0053Swedish Cancer Society, 19 0054Swedish Cancer Society, 21 1856Knut and Alice Wallenberg Foundation, KAW 2015.0114Swedish Research Council, 2018-02594Cancerforskningsfonden i Norrland, 22-2302Cancerforskningsfonden i Norrland, 21-2258
Available from: 2022-12-05 Created: 2022-12-05 Last updated: 2022-12-05Bibliographically approved
Josefsson, A. (2022). Little support for a protective effect of ADT against COVID-19. Scandinavian journal of urology, 56(2), 112-113
Open this publication in new window or tab >>Little support for a protective effect of ADT against COVID-19
2022 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 2, p. 112-113Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Taylor & Francis Group, 2022
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-202712 (URN)10.1080/21681805.2022.2033313 (DOI)000753284700001 ()35137649 (PubMedID)2-s2.0-85124360145 (Scopus ID)
Note

Editorial comment to the accepted article: "Androgen deprivation therapy, comorbidity, cancer stage and mortality from COVID-19 in men with prostate cancer", by Rolf Gedeborg, Lars Lindhagen, Stacy Loeb, Johan Styrke, Hans Garmo, Par Stattin. DOI: 10.1080/21681805.2021.2019304

Available from: 2023-01-13 Created: 2023-01-13 Last updated: 2023-01-16Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2013-0887

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