| 1. |
- Bill-Axelson, Anna, et al.
(författare)
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Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
- 2008
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Fall, Katja, et al.
(författare)
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Prostate-specific antigen levels as a predictor of lethal prostate cancer
- 2007
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Ingår i: Journal of the National Cancer Institute. - Oxford : Oxford Univ. Press. - 0027-8874 .- 1460-2105. ; 99:7, s. 526-532
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rates of long-term survival among patients with untreated localized prostate cancer are high. To avoid unnecessary treatment, tools are needed to identify the small proportion of patients who are destined to develop lethal prostate cancer. Methods: To evaluate the accuracy of early changes in prostate-specific antigen (PSA) levels as predictors of prostate cancer outcome, we assessed serial measurements of PSA level among 267 men with localized prostate cancer in a Scandinavian cohort of men who were diagnosed between 1989 and 1999 and who were managed by watchful waiting. We then 1) fitted individual regression lines to the PSA values assessed for each patient during the first 2 years of follow-up by using three different models, 2) evaluated early PSA curve characteristics as determinants of the cumulative incidence of lethal prostate cancer and calculated hazard ratios for baseline PSA value and rate of change in PSA level to prostate cancer outcome, and 3) plotted time-dependent receiver operating characteristic (ROC) curves. All P values are two-sided. Results: During complete follow-up for a mean of 8.5 years, 34 patients (13%) died from prostate cancer, and 18 (7%) developed metastases but were still alive at end of follow-up. In a log-linear model, both PSA value at baseline (P = .05) and the rate of PSA change (P<.001) were associated with the development of lethal prostate cancer. In the ROC analysis, however, the accuracy of classifying the disease as either indolent or destined to progress was low, regardless of the cut point chosen for initial PSA level or rate of change in PSA level. Conclusions: Although baseline PSA value and rate of PSA change are prognostic factors for lethal prostate cancer, they are poor predictors of lethal prostate cancer among patients with localized prostate cancer who are managed by watchful waiting.
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| 3. |
- Helgesen, Fred, et al.
(författare)
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Trends in prostate cancer survival in Sweden, 1960 through 1988 : Evidence of increasing diagnosis of nonlethal tumors
- 1996
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Ingår i: Journal of the National Cancer Institute. - 0027-8874 .- 1460-2105. ; 88:17, s. 1216-1221
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The incidence of prostate cancer has increased during the past 30 years but has been paralleled by increases in survival rates from this disease, despite the absence of documented major improvement in curative treatment. Since a high prevalence of microscopic prostate cancer has been observed in autopsied men and because many prostate cancers may never surface clinically, increased diagnostic activities might have led to increased detection of less aggressive tumors. PURPOSE: This study was conducted to elucidate whether the trends in prostate cancer incidence and patient survival may be due to increasing diagnoses of nonlethal tumors. METHODS: We analyzed a population-based cohort comprising all cases of prostate cancer (n = 80,901) detected in Sweden during the period of 1960 through 1988. Five hundred eighteen patients (0.64% of the total number) who could not be followed because of emigration or an incomplete national registration number were excluded. Observed and relative survival rates were calculated for the entire cohort of 80,383 assessable patients per 5-year age group in 5-year periods of diagnosis and according to diagnostic method and were compared between geographic areas with differences in incidence rates. To estimate the independent effects of these determinants, multivariate analyses were performed. RESULTS: For the 80,383 patients with complete follow-up, the 10- and 20-year observed survival rates were 17.5% (95% confidence interval [CI] = 17.2%-17.9%) and 3.5% (95% CI = 3.2%-3.7%), and the relative survival rates were 41.1% (95% CI = 40.3%-41.9%) and 28.6% (95% CI = 26.5%-30.1%), respectively. Relative survival rates improved markedly over time; 10-year relative survival rates increased from 29% (95% CI = 27%-31%) among case patients diagnosed in 1960 through 1964 to 45% (95% CI = 43%-46%) among those diagnosed in 1975 through 1979. Relative survival rates leveled off after about 18 years at 18% (95% CI = 15%-20%) among patients diagnosed in 1960 through 1964 and at 31% (95% CI = 28%-34%) among those diagnosed in 1970 through 1974. An even more favorable outlook was observed in those case patients diagnosed later. In areas with a high or low incidence of prostate cancer, the 10-year relative survival rates were 45% (95% CI = 44%-47%) and 36% (95% CI = 34%-38%), respectively. In the early 1960s, the calculated loss of life expectancy after diagnosis varied from about 68% (95% CI = 61%-75%) of the expected length of life in the youngest age group to about 48% (95% CI = 46%-50%) in the oldest age group. From 1960 through 1964 to 1985 through 1988, the loss of life expectancy decreased by more than 50% in all age groups. The differences in relative survival rates between age groups were small, with a gradual decrease in age groups more than 60-64 years of age. CONCLUSIONS: Most of the great temporal improvement and geographic variation in survival rates are quantitatively consistent, with likely increases in the rate of detection of nonlethal tumors. IMPLICATIONS: The increase in relative survival rates must be taken into consideration when evaluating the outcome of treatment of prostate cancer, since nonrandomized comparisons may be confounded by time trends. Diagnosis of nonlethal tumors raises concerns because the individual would suffer from the psychologic burden of a cancer diagnosis without any therapeutic benefit.
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| 4. |
- Setlur, Sunita R., et al.
(författare)
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Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer
- 2008
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Ingår i: Journal of the National Cancer Institute. - Oxford : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:11, s. 815-825
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The majority of prostate cancers harbor gene fusions of the 5'-untranslated region of the androgen-regulated transmembrane protease serine 2 (TMPRSS2) promoter with erythroblast transformation-specific transcription factor family members. The common fusion between TMPRESS2 and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion. METHODS: We used complementary DNA-mediated annealing, selection, ligation, and extension to determine the expression profiles of 6144 transcriptionally informative genes in archived biopsy samples from 455 prostate cancer patients in the Swedish Watchful Waiting cohort (1987-1999) and the United States-based Physicians(') Health Study cohort (1983-2003). A gene expression signature for prostate cancers with the TMPRSS2-ERG fusion was determined using partitioning and classification models and used in computational functional analysis. Cell proliferation and TMPRSS2-ERG expression in androgen receptor-negative (NCI-H660) prostate cancer cells after treatment with vehicle or estrogenic compounds were assessed by viability assays and quantitative polymerase chain reaction, respectively. All statistical tests were two-sided. RESULTS: We identified an 87-gene expression signature that distinguishes TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity (area under the curve = 0.80, 95% confidence interval [CI] = 0.792 to 0.81; P < .001). Computational analysis suggested that this fusion signature was associated with estrogen receptor (ER) signaling. Viability of NCI-H660 cells decreased after treatment with estrogen (viability normalized to day 0, estrogen vs vehicle at day 8, mean = 2.04 vs 3.40, difference = 1.36, 95% CI = 1.12 to 1.62) or ERbeta agonist (ERbeta agonist vs vehicle at day 8, mean = 1.86 vs 3.40, difference = 1.54, 95% CI = 1.39 to 1.69) but increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at day 8, mean = 4.36 vs 3.40, difference = 0.96, 95% CI = 0.68 to 1.23). Similarly, expression of TMPRSS2-ERG decreased after ERbeta agonist treatment (fold change over internal control, ERbeta agonist vs vehicle at 24 hours, NCI-H660, mean = 0.57- vs 1.0-fold, difference = 0.43-fold, 95% CI = 0.29- to 0.57-fold) and increased after ERalpha agonist treatment (ERalpha agonist vs vehicle at 24 hours, mean = 5.63- vs 1.0-fold, difference = 4.63-fold, 95% CI = 4.34- to 4.92-fold). CONCLUSIONS: TMPRSS2-ERG fusion prostate cancer is a distinct molecular subclass. TMPRSS2-ERG expression is regulated by a novel ER-dependent mechanism.
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| 5. |
- Stattin, Pär, et al.
(författare)
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Outcomes in localized prostate cancer: National Prostate Cancer Register of Sweden follow-up study.
- 2010
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102:13, s. 950-8
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Tidskriftsartikel (refereegranskat)abstract
- Treatment for localized prostate cancer remains controversial. To our knowledge, there are no outcome studies from contemporary population-based cohorts that include data on stage, Gleason score, and serum levels of prostate-specific antigen (PSA).
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