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Predictors of early androgen deprivation treatment failure in prostate cancer with bone metastases
Linköping University, Department of Clinical and Experimental Medicine, Urology. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
EpiStat, Sweden.
Karolinska Institute, Sweden.
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2016 (English)In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 5, no 3, 407-414 p.Article in journal (Refereed) Published
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Text
Abstract [en]

Approximately 15% of men with hormone naive metastatic prostate cancer primarily fail to respond to androgen deprivation treatment (ADT). The reason why the response to ADT differs in this subgroup of men with prostate cancer remains unclear. The aim of this study was to describe the characteristics of these men and to thereby define predictors of early ADT failure in prostate cancer patients with bone metastases. The study was based on 915 men from the prospective randomized multicenter trial (no. 5) conducted by the Scandinavian Prostate Cancer Group comparing parenteral estrogen with total androgen blockade. Early ADT failure was defined as death from metastatic prostate cancer within 12months after the start of ADT. Multivariate logistic regression models were applied to identify clinical predictors of early ADT failure. Ninety-four (10.3%) men were primarily nonresponders to ADT. Independent predictors of early ADT failure were poor Eastern Cooperative Oncology Group performance status (PS), analgesic consumption, low hemoglobin, and high Soloway score (extent of disease observed on the scan), in where patients with poor PS and/or high analgesic consumption had a threefold risk of early ADT failure. Not significantly factors related to early ADT failure were age, treatment, cardiovascular comorbidity, T category, grade of malignancy, serum estrogen level, and SHBG at enrolment. We analyzed characteristics of a subgroup of patients who primarily failed to respond to ADT. Four independent clinical predictors of early ADT failure could be defined, and men exhibiting these features should be considered for an alternative treatment.

Place, publisher, year, edition, pages
WILEY-BLACKWELL , 2016. Vol. 5, no 3, 407-414 p.
Keyword [en]
Androgen deprivation treatment; bone metastases; clinical predictors; early failure; prostate cancer
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-127443DOI: 10.1002/cam4.594ISI: 000373203000003PubMedID: 26765317OAI: oai:DiVA.org:liu-127443DiVA: diva2:925215
Note

Funding Agencies|Ferring AB Malmo, Sweden; Ferring Laegemidler A/S Copenhagen, Denmark; Pharmacia AB, Uppsala, Sweden; Schering-Plough AB, Stockholm, Sweden

Available from: 2016-04-30 Created: 2016-04-26 Last updated: 2017-11-30
In thesis
1. Disease-Specific Survival in Prostate Cancer Patients: Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data
Open this publication in new window or tab >>Disease-Specific Survival in Prostate Cancer Patients: Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction

Prostate cancer (PCa) is the most common cancer among men in Sweden. The clinical course varies considerably, which makes it difficult to predict the prognosis in the individual case. In order to explore the early as well as the late course of the disease, large study groups and population-based cohorts are necessary.

Aims

  • To explore factors that influence the long-term outcome of men with low-risk tumours in a population-based register, to predict the long-term course, and to assess the mortality rate for men with prostate cancer (Paper I)
  • To analyse long-term outcome and to investigate factors associated with long-term survival in patients with metastases to the skeleton (Paper II)
  • To analyse early androgen deprivation treatment (ADT) failure and to define clinical predictors associated with short survival due to early ADT failure in prostate cancer patients with bone metastases (Paper III)
  • To analyse the prognostic significance of the extent of bone metastases in relation to other pretreatment variables in prostate cancer patients, and to explore the impact of bone metastases on quality-of-life (Paper IV)

Material and methods

The study groups were assembled from The South East Region Prostate Cancer Register (SERPCR), and The Scandinavian Prostate Cancer Group (SPCG) Trial No. 5. In the first study, prognostic factors and long-term disease-specific mortality rates of low-risk prostate cancer patients from the early PSA era were analysed. In the second study, patient-related factors, quality-of-life (QoL) and long-term survival in 915 PCa patients with bone metastases (M1b) under ADT, were analysed. In Study III factors predicting primary failure to respond to ADT were identified. Study IV explored the impact of the extent of bone metastases on survival and QoL for these men.

Result and conclusions

The long-term disease-specific mortality of low-risk localised PCa is low, but the annual mortality rate gradually increases. This indicates that some tumours slowly develop into lethal cancer, particularly in men 70 years or older and with a PSA level ≥ 4 μg/L. From the SPCG Trial No. 5, a subgroup of patients with M1b disease and favourable set of predictive factors survived more than 10 years under ADT with an acceptable QoL. Independent predictors of long-term survival were identified as performance status (PS) < 2, limited extent of bone metastases, and a PSA level < 231 μg/L at the time of enrolment in the trial. However, four independent clinical predictors of early ADT failure could be defined. Men exhibiting these features should be considered for an alternative treatment. Patient grouping based on three categories of extent of bone metastases related to PS, haemoglobin, and QoL at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 96 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1527
Keyword
Androgen deprivation treatment; bone metastases; early failure; extent of disease; hormone-naïve; long-term disease-specific survival; low-risk; mortality; quality-of-life; predictors of survival; prostate cancer.
National Category
Urology and Nephrology Cancer and Oncology Surgery Orthopedics Family Medicine
Identifiers
urn:nbn:se:liu:diva-132385 (URN)10.3384/diss.diva-132385 (DOI)9789176857168 (ISBN)
Public defence
2016-11-11, Berzeliussalen, Campus US, Linköping, 13:00 (Swedish)
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Available from: 2016-11-07 Created: 2016-11-07 Last updated: 2016-11-07Bibliographically approved

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Varenhorst, Eberhard

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UrologyFaculty of Health SciencesDepartment of Urology in ÖstergötlandDepartment of Clinical and Experimental MedicineFaculty of Medicine and Health Sciences
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