| 1. |
- Rueenauver, K., et al.
(författare)
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Prognostic significance of YWHAZ expression in localized prostate cancer
- 2014
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 17:4, s. 310-314
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer (PCa) patients are often over-treated because of the lack of biomarkers needed to distinguish the lethal from the indolent form of PCa. YWHAZ was recently identified as a potential therapeutic target in castration-resistant PCa (CRPC). Therefore, this study focused on determining the prognostic significance of YWHAZ in localized PCa.METHODS: YWHAZ expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded tissue from 213 men who underwent radical prostatectomy. Kaplan-Meier analysis and Cox proportional-hazards models were, used to assess the prognostic value of YWHAZ intensity.RESULTS: High YWHAZ expression was strongly associated with high Gleason score at the time of diagnosis (P<0.001) and PSA relapse (P=0.001). Importantly, patients with high expression of YWHAZ had a higher risk of CRPC development (P=0.002) and reduced survival time (P=0.002).CONCLUSIONS: Our findings indicate that YWHAZ could serve as a promising prognostic biomarker in localized PCa to predict poor prognosis and to identify a subgroup of tumors, which might benefit from earlier adjuvant or YWHAZ-targeted therapy.
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| 2. |
- Adolfsson, Jan, et al.
(författare)
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Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005 : Data from the national prostate cancer register in Sweden
- 2007
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Ingår i: Scandinavian Journal of Urology and Nephrology. - Stockholm : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer
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| 3. |
- Ali, Imran, et al.
(författare)
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Exposure to polychlorinated biphenyls and prostate cancer : population-based prospective cohort and experimental studies
- 2016
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 37:12, s. 1144-1151
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Tidskriftsartikel (refereegranskat)abstract
- Polychlorinated biphenyls (PCBs) are highly persistent environmental pollutants and are undesirable components of our daily food. PCBs are classified as human carcinogens, but the evidence for prostate cancer is limited and available data are inconsistent. We explored the link between non-dioxin-like PCB and grade of prostate cancer in a prospective cohort as well as in cell experiments. A population-based cohort of 32496 Swedish men aged 45-79 years was followed prospectively through 1998-2011, to assess the association between validated estimates of dietary PCB exposure and incidence of prostate cancer by grade (2789 cases, whereof 1276 low grade, 756 intermediate grade, 450 high grade) and prostate cancer mortality (357 fatal cases). In addition, we investigated a non-dioxin-like PCB153-induced cell invasion and related markers in normal prostate stem cells (WPE-stem) and in three different prostate cancer cell lines (PC3, DU145 and 22RV1) at exposure levels relevant to humans. After multivariable-adjustment, dietary PCB exposure was positively associated with high-grade prostate cancer, relative risk (RR) 1.35 [95% confidence interval (CI): 1.03-1.76] and with fatal prostate cancer, RR 1.43 (95% CI: 1.05-1.95), comparing the highest tertile with the lowest. We observed no association with low or intermediate grade of prostate cancer. Cell invasion and related markers, including MMP9, MMP2, Slug and Snail, were significantly increased in human prostate cancer cells as well as in prostate stem cells after exposure to PCB153. Our findings both from the observational and experimental studies suggest a role of non-dioxin-like PCB153 in the development of high-grade and fatal prostate cancer.
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| 4. |
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| 5. |
- Andrén, Ove, 1963-, et al.
(författare)
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How well does the Gleason score predict prostate cancer death? : A 20-year followup of a population based cohort in Sweden
- 2006
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Ingår i: Journal of Urology. - Baltimore : Williams and Wilkins Co.. - 0022-5347 .- 1527-3792. ; 175:4, s. 1337-1340
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Adenocarcinoma of the prostate is the most common cancer among men in Western countries. Although the prognostic heterogeneity of prostate cancer is enormous, clinically insignificant aggressive prostate cancers cannot be reliably distinguished. Therefore, identifying prognostic factors is increasingly important, notably among men diagnosed with localized prostate cancer, because many of them may not require aggressive treatment. Materials and Methods We analyzed a population based cohort of 253 men with early stage (T1a-b, Nx, M0) initially untreated prostate cancer diagnosed between 1977 and 1991, before PSA screening was available. Tissue samples were available for 240 patients diagnosed with transurethral resection. During complete followup through September 2003, standardized criteria were used to classify histopathological characteristics, progression and causes of death. Results Higher Gleason grade, higher nuclear grade and larger tumor volume were independent predictors of death in prostate cancer with monotonous and statistically significant trends (p <0.05). In contrast, the level of Ki-67 – strongly correlated to Gleason score – was not an independent predictor of prostate cancer death. Given a Gleason score of 7 or greater, the probability of dying of prostate cancer was 29%. The corresponding predictive value for Gleason score 8 or greater was 48%. Conclusions Although a high Gleason score is a determinant of prostate cancer death, its PPV is relatively low. Thus, further efforts in finding other or complementary indicators of prostate cancer outcome are needed.
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| 6. |
- Andrén, Ove, 1963-, et al.
(författare)
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MUC-1 gene is associated with prostate cancer death : a 20-year follow-up of a population-based study in Sweden
- 2007
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Ingår i: British Journal of Cancer. - London : Harcourt Publishers. - 0007-0920 .- 1532-1827. ; 97:6, s. 730-734
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Tidskriftsartikel (refereegranskat)abstract
- Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score >=7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3–128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.
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| 7. |
- Andrén, Ove, 1963-
(författare)
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Natural history and prognostic factors in localized prostate cancer
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The natural history of localized prostate cancer is not fully understood. In most patients the tumor will never progress to a lethal disease, while a subset of patients will ultimately die of the disease. Efficient tools to separate indolent from lethal disease is currently lacking which means that many patients will be offered treatment without any benefit, but still be at risk of experiencing treatment related side effects. The aims of these studies were to get more insight into the natural history of untreated localized prostate cancer, to assess the prognostic value of established clinical parameters such as Gleason score, nuclear grade and tumor volume and, moreover, some new prognostic markers Ki-67, AMACR and MUC-1. We also aimed to study time trends in the detection of incidental tumors in Sweden. Patients with localized disease (n=223) and no initial treatment were followed for 21 years. Most patients had a favorable outcome. However, a subset of patients developed lethal disease even beyond 15 years of follow-up and these patients define the group that may benefit most from treatment with curative intent. Patients with poorly differentiated tumors experienced a 9 time higher risk of dying in prostate cancer. The studies on prognostic markers are based on a cohort of patients (n=253) with incidental prostate cancer detected by transurethral resection for presumed benign hyperplasia. All patients were left without initial treatment. Gleason grade, nuclear grade and tumor volume turned all out to be independent prognostic factors. MUC-1, AMACR and Ki-67 also carried prognostic information. However, after adjustment for Gleason grade, nuclear grade and tumor volume only MUC-1 and AMACR remained as statistically significant prognostic factors. When tested for sensitivity and specificity they all failed and, consequently, they seem to be of less value in daily practice for cancelling an individual patient regarding the choice of treatment. Time trends in incidental prostate tumors in Sweden were analyzed in a cohort of patients with prostate tumors detected by transurethral resection (TUR-P). Through linkage of the national registration number (NRN) with several registers, e.g. the Swedish Cancer Registry, the National Inpatient registry and the Cause of Death Registry we identified, during the period 1970 through 2003, in total 23288 patients with incidental prostate cancer, who constituted the study group. As comparison group we choose all patients diagnosed with prostate cancer between 1970-2003 excluding those with incidental cancer, in total 112204 patients. Our result confirms earlier findings that there has been a dramatic change over time in incidence of incidental prostate cancers in Sweden, which parallels the introduction of prostate specific antigen. We also found that the cumulative incidence of prostate cancer death is high in the incidental group, opposing earlier findings that incidental tumours are a non-lethal disease.
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| 8. |
- Bill-Axelson, Anna, et al.
(författare)
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Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer
- 2014
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Ingår i: New England Journal of Medicine. - Waltham : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 370:10, s. 932-942
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRadical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. MethodsBetween 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. ResultsDuring 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). ConclusionsExtended 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 ...
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| 9. |
- Bill-Axelson, Anna, et al.
(författare)
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Radical Prostatectomy or Watchful Waiting in Prostate Cancer-29-Year Follow-up
- 2018
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Ingår i: New England Journal of Medicine. - : Massachussetts Medical Society. - 0028-4793 .- 1533-4406. ; 379:24, s. 2319-2329
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term followup is sparse. METHODS We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model. RESULTS By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer). CONCLUSIONS Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer.
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| 10. |
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