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Holmberg, Lars
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Publications (10 of 11) Show all publications
Bill-Axelson, A., Holmberg, L., Garmo, H., Rider, J. R., Taari, K., Busch, C., . . . Johansson, J.-E. (2014). Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer. New England Journal of Medicine, 370(10), 932-942
Open this publication in new window or tab >>Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer
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2014 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 10, p. 932-942Article in journal (Refereed) Published
Abstract [en]

Background: Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain.

Methods: Between 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy.

Results: During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04).

Conclusions: Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.)

The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...

Place, publisher, year, edition, pages
Waltham: Massachusetts Medical Soc., 2014
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-35215 (URN)10.1056/NEJMoa1311593 (DOI)000332309800010 ()24597866 (PubMedID)2-s2.0-84895473498 (Scopus ID)
Funder
Swedish Cancer Society, 07 05 12 09 05 12NIH (National Institute of Health), 1ROI CA 108746-O1A1
Note

Funding Agencies:

Karolinska Institutet 2368/10-221

Prostate Cancer Foundation

Percy Falk Foundation

Available from: 2014-06-03 Created: 2014-06-02 Last updated: 2018-09-07Bibliographically approved
Botling, J., Edlund, K., Lohr, M., Hellwig, B., Holmberg, L., Lambe, M. G., . . . Micke, P. (2013). Biomarker Discovery in Non-Small Cell Lung Cancer: Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation. Clinical Cancer Research, 19(1), 194-204
Open this publication in new window or tab >>Biomarker Discovery in Non-Small Cell Lung Cancer: Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation
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2013 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 19, no 1, p. 194-204Article in journal (Refereed) Published
Abstract [en]

Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.

Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).

Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate < 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.

Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194-204. (c) 2012 AACR.

National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-38714 (URN)10.1158/1078-0432.CCR-12-1139 (DOI)000313051100021 ()23032747 (PubMedID)2-s2.0-84871959921 (Scopus ID)
Note

Funding agencies are:

Swedish Cancer Society  

Lions Cancer Foundation, Uppsala, Sweden  

German Research Foundation (DFG) RA 870/4-1, RA 870/5-1 

Astra Zeneca  

Knut and Alice Wallenberg Foundation 

Available from: 2014-11-18 Created: 2014-11-18 Last updated: 2018-08-27Bibliographically approved
Fall, K., Holmberg, L. & Sundström, J. (2013). Good prognosis studies can provide better clinical decisions. Validated risk-/prognosis factors helps the physician. Läkartidningen, 110(6), 279-283
Open this publication in new window or tab >>Good prognosis studies can provide better clinical decisions. Validated risk-/prognosis factors helps the physician
2013 (English)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 6, p. 279-283Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:oru:diva-32999 (URN)
Available from: 2014-01-09 Created: 2014-01-09 Last updated: 2017-12-06Bibliographically approved
Holmberg, L., Bill-Axelsson, A., Steineck, G., Garmo, H., Palmgren, J., Johansson, E., . . . Johansson, J.-E. (2012). Results from the scandinavian prostate cancer group trial number 4: a randomized controlled trial of radical prostatectomy versus watchful waiting. Journal of the National Cancer Institute. Monographs, 2012(45), 230-233
Open this publication in new window or tab >>Results from the scandinavian prostate cancer group trial number 4: a randomized controlled trial of radical prostatectomy versus watchful waiting
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2012 (English)In: Journal of the National Cancer Institute. Monographs, ISSN 1052-6773, E-ISSN 1745-6614, Vol. 2012, no 45, p. 230-233Article in journal (Refereed) Published
Abstract [en]

In the Scandinavian Prostate Cancer Group Trial Number 4 (SPCG-4), 347 men were randomly assigned to radical prostatectomy and 348 to watchful waiting. In the most recent analysis (median follow-up time = 12.8 years), the cumulative mortality curves had been stable over the follow-up. At 15 years, the absolute risk reduction of dying from prostate cancer was 6.1% following randomization to radical prostatectomy, compared with watchful waiting. Hence, 17 need to be randomized to operation to avert one death. Data on self-reported symptoms, stress from symptoms, and quality of life were collected at 4 and 12.2 years of median follow-up. These questionnaire studies show an intricate pattern of symptoms evolving after surgery, hormonal treatments, signs of tumor progression, and also from natural aging. This article discusses some of the main findings of the SPCG-4 study. The Scandinavian Prostate Cancer Group Trial Number 4 (SPCG-4) started in 1989 when radical prostatectomy was newly introduced in Scandinavia and when there was essentially no prostate-specific antigen (PSA) testing in asymptomatic men; such testing only became common at the end of the inclusion of the trial a decade later. However, the trial data continue to be important for several reasons. In many parts of the world, the clinical panorama of prostate cancer still resembles that in Sweden in the early 1990s. The trial results point to many of the issues that modern diagnosis and treatment have to solve. SPCG-4 is to date the only trial to inform about both forces of mortality and self-reported symptoms and quality of life in men after radical prostatectomy or watchful waiting two decades and more out after a primary diagnosis of prostate cancer. According to the protocol (http://www.roc.se/prostata/SPCG-4.pdf), the main trial data have been updated every 3 years since 2002 (1–6). In this presentation, we highlight some of the main findings with bearing on the topic of this conference and discuss some issues that have been raised when the trial results have been presented.

Place, publisher, year, edition, pages
Cary, USA: Oxford University Press, 2012
National Category
Medical and Health Sciences Cancer and Oncology Urology and Nephrology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-27457 (URN)10.1093/jncimonographs/lgs025 (DOI)23271778 (PubMedID)2-s2.0-84871757326 (Scopus ID)
Available from: 2013-02-06 Created: 2013-02-06 Last updated: 2018-05-12Bibliographically approved
Johansson, E., Steineck, G., Holmberg, L., Johansson, J.-E., Nyberg, T., Ruutu, M. & Bill-Axelsson, A. (2011). Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial. The Lancet Oncology, 12(9), 891-899
Open this publication in new window or tab >>Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial
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2011 (English)In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 12, no 9, p. 891-899Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years.

METHODS: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint.

FINDINGS: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7-17) and a median age of 77·0 years (range 61-88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07-1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life.

INTERPRETATION: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information.

Place, publisher, year, edition, pages
Elsevier, 2011
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-27435 (URN)10.1016/S1470-2045(11)70162-0 (DOI)000294293500020 ()21821474 (PubMedID)2-s2.0-80052368164 (Scopus ID)
Funder
Swedish Cancer Society
Note

Funding Agencies:

US National Institutes of Health  R01 CA108746-01A1

Foundation in Memory of Johanna Hagstrand and Sigfrid Linner

Available from: 2013-02-06 Created: 2013-02-06 Last updated: 2018-09-14Bibliographically approved
Tilling, K., Garmo, H., Metcalfe, C., Holmberg, L., Hamdy, F. C., Neal, D. E., . . . Donovan, J. L. (2010). Development of a new method for monitoring prostate-specific antigen changes in men with localised prostate cancer: a comparison of observational cohorts. European Urology, 57(3), 446-452
Open this publication in new window or tab >>Development of a new method for monitoring prostate-specific antigen changes in men with localised prostate cancer: a comparison of observational cohorts
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2010 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, no 3, p. 446-452Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Prostate-specific antigen (PSA) measurements are increasingly used to monitor men with localised prostate cancer (PCa), but there is little consensus about the method to use. OBJECTIVE: To apply age-specific predictions of PSA level (developed in men without cancer) to one cohort of men with clinically identified PCa and one cohort of men with PSA-detected PCa. We hypothesise that among men with clinically identified cancer, the annual increase in PSA level would be steeper than in men with PSA-detected cancer. DESIGN, SETTING, AND PARTICIPANTS: The Scandinavian Prostate Cancer Group 4 (SPCG-4) cohort consisted of 321 men assigned to the watchful waiting arm of the SPCG-4 trial. The UK cohort consisted of 320 men with PSA-detected PCa in the Prostate testing for cancer and Treatment (ProtecT) study who opted for monitoring. Multilevel models describing changes in PSA level were fitted to the two cohorts, and average PSA level at age 50, change in PSA level with age, and predicted PSA values were derived. MEASUREMENTS: PSA level. RESULTS AND LIMITATIONS: In the SPCG-4 cohort, mean PSA at age 50 was similar to the cancer-free cohort but with a steeper yearly increase in PSA level (16.4% vs 4.0%). In the UK cohort, mean PSA level was higher than that in the cancer-free cohort (due to a PSA biopsy threshold of 3.0 ng/ml) but with a similar yearly increase in PSA level (4.1%). Predictions were less accurate for the SPCG-4 cohort (median difference between observed and predicted PSA level: -2.0 ng/ml; interquartile range [IQR]: -7.6-0.7 ng/ml) than for the UK cohort (median difference between observed and predicted PSA level: -0.8 ng/ml; IQR: -2.1-0.1 ng/ml). CONCLUSIONS: In PSA-detected men, yearly change in PSA was similar to that in cancer-free men, whereas in men with symptomatic PCa, the yearly change in PSA level was considerably higher. Our method needs further evaluation but has promise for refining active monitoring protocols.

National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-12131 (URN)10.1016/j.eururo.2009.03.023 (DOI)000273988700014 ()19303695 (PubMedID)
Available from: 2010-10-07 Created: 2010-10-07 Last updated: 2018-02-27Bibliographically approved
Ahlin, C., Zhou, W., Holmqvist, M., Holmberg, L., Nilsson, C., Jirström, K., . . . Fjällskog, M.-L. (2009). Cyclin A is a proliferative marker with good prognostic value in node-negative breast cancer. Cancer Epidemiology, Biomarkers and Prevention, 18(9), 2501-2506
Open this publication in new window or tab >>Cyclin A is a proliferative marker with good prognostic value in node-negative breast cancer
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2009 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 9, p. 2501-2506Article in journal (Refereed) Published
Abstract [en]

Background: Proliferative markers are not recommended as prognostic factors for clinical use in breast cancer due to lack of standardization in methodology. However, proliferation is driving several gene expression signatures emphasizing the need for a reliable proliferative marker IF or clinical use. Studies suggest that cyclin A is a prognostic marker with satisfying reproducibility. We investigated cyclin A as a prognostic marker in node-negative breast cancer using previously defined cutoff values. Patients and Methods: In a case-control study, we defined 190 women who died from breast cancer as cases and 190 women alive at the time for the corresponding case's death as controls. Inclusion criteria were tumor size <= 50 mm, no lymph node metastases and no adjuvant chemotherapy. Tumor tissues were immunostained for cyclin A using commercially available antibodies. Results: We found a statistically significant association between expression of cyclin A and breast cancer death in a univariate model: odds ratio for cyclin A(ave) 2.7 [95% confidence interval (CI), 1.7-4.3] and cyclin A(max) 3.4 (CI, 2.1-5.5). Corresponding odds ratio for Ki67 were Ki67(ave) 1.9 (CI, 1.2-3.1) and Ki67(max) 1.7 (CI, 1.1-2.7) and for grade 3.1 (CI, 1.8-5.1). Cyclin A was strongly correlated to Ki67 and grade why a model including all was not appropriate. Conclusions: Cyclin A is a prognostic factor for breast cancer death in node-negative patients using standardized methodology regarding scoring and cutoff values. Adding cyclin A as a proliferative marker to established clinicopathologic factors will improve the separation of low and high risk breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2501-6)

National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-19185 (URN)10.1158/1055-9965.EPI-09-0169 (DOI)000269734100023 ()
Available from: 2011-10-05 Created: 2011-10-04 Last updated: 2017-12-08Bibliographically approved
Mucci, L. A., Pawitan, Y., Demichelis, F., Fall, K., Stark, J. R., Adami, H.-O., . . . Rubin, M. A. (2008). Nine-gene molecular signature is not associated with prostate cancer death in a watchful waiting cohort. Cancer Epidemiology, Biomarkers and Prevention, 17(1), 249-251
Open this publication in new window or tab >>Nine-gene molecular signature is not associated with prostate cancer death in a watchful waiting cohort
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2008 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 1, p. 249-251Article in journal (Refereed) Published
Abstract [en]

Tumor molecular markers hold promise to distinguish potentially lethal from indolent prostate cancer and to guide treatment choices. A previous study identified a nine-gene molecular signature in tumors associated with prostate-specific antigen relapse after prostatectomy. We examined this molecular model in relation to prostate cancer death among 172 men with initially localized disease. We quantified protein expression of the nine genes in tumors to classify progression risk. Accounting for clinical prognostic factors, the nine-gene model did not provide discrimination to predict lethal and indolent prostate cancer.

Place, publisher, year, edition, pages
Baltimore: Waverly Press, 2008
Keywords
Aged, Cohort Studies, Gene Expression Profiling/*methods, Humans, Immunoenzyme Techniques, Male, Prostate-Specific Antigen/blood, Prostatic Neoplasms/epidemiology/*metabolism/*mortality, Survival Rate, Tissue Array Analysis, Tumor Markers; Biological/*metabolism
National Category
Medical and Health Sciences Cancer and Oncology Urology and Nephrology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-3673 (URN)10.1158/1055-9965.EPI-07-0722 (DOI)18199732 (PubMedID)
Available from: 2008-12-17 Created: 2008-12-17 Last updated: 2017-12-14Bibliographically approved
Bill-Axelson, A., Holmberg, L., Filén, F., Ruutu, M., Garmo, H., Busch, C., . . . Johansson, J.-E. (2008). Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. Journal of the National Cancer Institute, 100(16), 1144-1154
Open this publication in new window or tab >>Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial
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2008 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, no 16, p. 1144-1154Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.

METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.

RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).

CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery. 

Keywords
Aged, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Staging, Odds Ratio, Proportional Hazards Models, Prostate-Specific Antigen/blood, Prostatectomy/methods, Prostatic Neoplasms/immunology/*mortality/pathology/*surgery, Research Design, Risk Assessment, Scandinavia/epidemiology, Time Factors
National Category
Medical and Health Sciences Surgery Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-3665 (URN)10.1093/jnci/djn255 (DOI)18695132 (PubMedID)
Available from: 2008-12-17 Created: 2008-12-17 Last updated: 2017-12-14Bibliographically approved
Mucci, L. A., Pawitan, Y., Demichelis, F., Fall, K., Stark, J. R., Adami, H.-O., . . . Rubin, M. A. (2008). Testing a multigene signature of prostate cancer death in the Swedish Watchful Waiting Cohort. Cancer Epidemiology, Biomarkers and Prevention, 17(7), 1682-1688
Open this publication in new window or tab >>Testing a multigene signature of prostate cancer death in the Swedish Watchful Waiting Cohort
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2008 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 7, p. 1682-1688Article in journal (Refereed) Published
Abstract [en]

Although prostate cancer is a leading cause of cancer death, most men die with and not from their disease, underscoring the urgency to distinguish potentially lethal from indolent prostate cancer. We tested the prognostic value of a previously identified multigene signature of prostate cancer progression to predict cancer-specific death. The Örebro Watchful Waiting Cohort included 172 men with localized prostate cancer of whom 40 died of prostate cancer. We quantified protein expression of the markers in tumor tissue by immunohistochemistry and stratified the cohort by quintiles according to risk classification. We accounted for clinical variables (age, Gleason, nuclear grade, and tumor volume) using Cox regression and calculated receiver operator curves to compare discriminatory ability. The hazard ratio of prostate cancer death increased with increasing risk classification by the multigene model, with a 16-fold greater risk comparing highest-risk versus lowest-risk strata, and predicted outcome independent of clinical factors (P = 0.002). The best discrimination came from combining information from the multigene markers and clinical data, which perfectly classified the lowest-risk stratum where no one developed lethal disease; using the two lowest-risk groups as reference, the hazard ratio (95% confidence interval) was 11.3 (4.0-32.8) for the highest-risk group and difference in mortality at 15 years was 60% (50-70%). The combined model provided greater discriminatory ability (area under the curve = 0.78) than the clinical model alone (area under the curve = 0.71; P = 0.04). Molecular tumor markers can add to clinical variables to help distinguish lethal and indolent prostate cancer and hold promise to guide treatment decisions. 

Place, publisher, year, edition, pages
Philadelphia: American Association for Cancer Research, 2008
Keywords
Aged, DNA; Neoplasm/*genetics, Follow-Up Studies, Gene Expression Profiling, Gene Expression Regulation; Neoplastic, Humans, In Situ Hybridization; Fluorescence, Male, Phenotype, Prognosis, Prostatic Neoplasms/metabolism/*mortality/pathology, Retrospective Studies, Serine Endopeptidases/biosynthesis/*genetics, Severity of Illness Index, Survival Rate/trends, Sweden/epidemiology, Time Factors
National Category
Medical and Health Sciences Surgery Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-3669 (URN)10.1158/1055-9965.EPI-08-0044 (DOI)18583469 (PubMedID)
Available from: 2008-12-17 Created: 2008-12-17 Last updated: 2017-12-14Bibliographically approved

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