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Disease-Specific Survival in Prostate Cancer Patients: Results from the Scandinavian Prostate Cancer Group (SPCG) Trial No. 5 and Regional Cancer Register Data
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
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 [en]
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: urn:nbn:se:liu:diva-132385DOI: 10.3384/diss.diva-132385ISBN: 9789176857168 (Print)OAI: oai:DiVA.org:liu-132385DiVA: diva2:1044795
Public defence
2016-11-11, Berzeliussalen, Campus US, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-11-07 Created: 2016-11-07 Last updated: 2016-11-07Bibliographically approved
List of papers
1. The Long-term Disease-specific Mortality of Low-risk Localized Prostate Cancer: A Prospective Population-based Register Study Over Two Decades
Open this publication in new window or tab >>The Long-term Disease-specific Mortality of Low-risk Localized Prostate Cancer: A Prospective Population-based Register Study Over Two Decades
2016 (English)In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 91, 77-82 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE To identify prognostic factors, and to estimate the long-term disease-specific and annual disease-specific mortality rates of low-risk prostate cancer patients from the early prostate-specific antigen (PSA) era. PATIENTS AND METHODS We studied data extracted from the Southeast Region Prostate Cancer Register in Sweden, on 1300 patients with clinically localized low-risk tumors, T1-2, PSA level amp;lt;= 10 mu g/L and Gleason scores 2-6 or World Health Organization Grade 1, diagnosed 1992-2003. The Cox multivariate regression model was used to evaluate factors predicting survival. Prostate cancer death rates per 1000 person-years were estimated for 4 consecutive follow-up time periods: 0-5, 5-10, 10-15, and 15+ years after diagnosis. RESULTS During the follow-up of overall survivors (mean 10.6 years; maximum 21.8 years), 93 patients (7%) died of prostate cancer. Cancer-specific survival was 0.98 (95% confidence interval [CI] 0.97-0.99), 0.95 (95% CI 0.93-0.96), 0.89 (95% CI 0.86-0.91), and 0.84 (95% CI 0.80-0.88), 5, 10, 15, and 20 years after diagnosis. The 5-year increases in cancer-specific mortality were statistically significant (P amp;lt;. 001). Patients with PSA amp;gt;= 4 mu g/L managed initially with watchful waiting and those aged 70 years or older had a significantly higher risk of dying from their prostate cancer. CONCLUSION The long-term disease-specific mortality of low-risk localized prostate cancer is low, but the annual mortality rate from prostate cancer gradually increases. This indicates that some tumors slowly develop into lethal cancer, particularly in patients 70 years or older with a PSA level amp;gt;= 4 mu g/L. (C) 2016 Elsevier Inc.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2016
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:liu:diva-129173 (URN)10.1016/j.urology.2016.01.033 (DOI)000375901500023 ()26879734 (PubMedID)
Available from: 2016-06-13 Created: 2016-06-13 Last updated: 2016-11-07
2. Clinical characteristics and quality-of-life in patients surviving a decade of prostate cancer with bone metastases
Open this publication in new window or tab >>Clinical characteristics and quality-of-life in patients surviving a decade of prostate cancer with bone metastases
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2016 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 6, 904-913 p.Article in journal (Refereed) Published
Abstract [en]

Objective To describe characteristics and quality-of-life (QoL), and to define factors associated with long-term survival in a subgroup of patients with prostate cancer with M1b disease. Patients and Methods The study was based on 915 patients from a prospective randomised multicentre trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Long-term survival was defined as patients having an overall survival of &gt;= 10 years, and logistic regression models were constructed to identity clinical predictors of survival. QoL during follow-up was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire - C30 version 1 (EORTC-C30) ratings. Results In all, 40 (4.4%) of the 915 men survived for &gt;10 years. Factors significantly associated with increased likelihood of surviving for &gt;10 years in the univariate analyses were: absence of cancer-related pain; Eastern Cooperative Oncology Group (ECOG) performance status of &lt;2; negligible analgesic consumption; T-category of 1-2; prostate-specific antigen (PSA) level of &lt;231 mu g/L; and a Soloway score of 1. In the multivariate analyses, ECOG performance status of &lt;2, PSA level of &lt;231 mu g/L, and Soloway score of 1, were all independent predictors of long-term survival. All subscales of the EORTC-C30 were higher in this group than for patients with short survival, but slowly declined over the decade. Conclusion A subgroup of patients with prostate cancer with M1b disease and certain characteristics showed a positive long-term response to androgen-deprivation therapy with an acceptable QoL over a decade or more. Independent predictors of long-term survival were identified as ECOG performance status of &lt;2, limited extent of bone metastases (Soloway score of 1), and a PSA level of &lt;231 mu g/L at the time of enrolment.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
Keyword
prostate cancer; bone metastases; long-term survival; quality-of-life
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-128927 (URN)10.1111/bju.13190 (DOI)000376009800015 ()26033416 (PubMedID)
Available from: 2016-06-09 Created: 2016-06-07 Last updated: 2016-11-07
3. Predictors of early androgen deprivation treatment failure in prostate cancer with bone metastases
Open this publication in new window or tab >>Predictors of early androgen deprivation treatment failure in prostate cancer with bone metastases
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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
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
Keyword
Androgen deprivation treatment; bone metastases; clinical predictors; early failure; prostate cancer
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127443 (URN)10.1002/cam4.594 (DOI)000373203000003 ()26765317 (PubMedID)
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: 2016-11-07
4. Clinical presentation and predictors of survival related to extent of bone metastasis in 900 prostate cancer patients
Open this publication in new window or tab >>Clinical presentation and predictors of survival related to extent of bone metastasis in 900 prostate cancer patients
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2016 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 5, 352-359 p.Article in journal (Refereed) Published
Abstract [en]

Objective: The aim of this study was to investigate the impact of bone metastasis on survival and quality of life (QoL) in men with hormone-naive prostate cancer. Materials and methods: The study included 900 patients from a randomized trial (No. 5) by the Scandinavian Prostate Cancer Group, comparing parenteral oestrogen with total androgen blockade. Extent of bone metastasis was categorized according to a modified Soloway score: score 1, n=319; score 2, n = 483; and score 3, n = 98 patients. The primary outcome measurements were mean differences in QoL and overall survival. Results: QoL rating scales showed a decrease with increasing extent of bone metastasis (p amp;lt; 0.001). The mean global health status decreased from 64.4 to 50.5 for Soloway score 1 and 3, respectively. Following adjustment for performance status, analgesic consumption, grade of malignancy, alkaline phosphatase, prostate-specific antigen, haemoglobin and global health status, Soloway score 2 and 3 had a 47% [hazard ratio (HR) 1.47, 95% confidence interval (CI) 1.21-1.80] and 78% (HR 1.78 95%, CI 1.32-2.42) increased mortality, respectively, compared to Soloway score 1. Independent predictive factors of mortality were assessed. Conclusions: Patient grouping based on three categories of extent of bone metastasis related to performance status, haemoglobin and global health status at presentation, as independent predictors of mortality, may provide improved accuracy of prognosis.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2016
Keyword
Androgen deprivation treatment; bone metastasis; extent of disease; hormone-naive; predictors of survival; prostate cancer
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:liu:diva-132207 (URN)10.1080/21681805.2016.1209689 (DOI)000384068000005 ()27603423 (PubMedID)
Note

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

Available from: 2016-11-01 Created: 2016-10-21 Last updated: 2016-11-30

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