| 1. |
|
|
| 2. |
|
|
| 3. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 4. |
|
|
| 5. |
- Arndt, D. S., et al.
(författare)
-
STATE OF THE CLIMATE IN 2017
- 2018
-
Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
-
Forskningsöversikt (refereegranskat)
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Haese, A., et al.
(författare)
-
A pre-specified model based on four kallikrein markers in blood improves predictions of adverse pathology and biochemical recurrence after radical prostatectomy
- 2020
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 123:4, s. 604-609
-
Tidskriftsartikel (refereegranskat)abstract
- Background A pre-specified model based on four kallikrein markers in blood, commercially available as 4Kscore, predicts Gleason Grade (GG) 3 + 4 or higher prostate cancer on biopsy. However, sampling error and variation in pathology reporting may miss aggressive disease. Methods The 4Kscore was measured in cryopreserved blood from 2330 men obtained before prostatectomy at a single institution between 2002 and 2010. Adverse surgical pathology and biochemical recurrence (BCR) were pre-specified to be assessed in all men, biopsy GG 3 + 3, and 3 + 4. Results Adjusted for established clinical predictors, the 4Kscore was significantly associated with adverse pathology (OR 1.49; 95% CI 1.32, 1.67;p < 0.0001). Adding 4Kscore increased discrimination from (AUC) 0.672 to 0.718 and 0.644 to 0.659 within biopsy GG 3 + 3 and 3 + 4, respectively. Higher 4Kscore was associated with higher risk of BCR (HR 1.16, 95% CI 1.06, 1.26;p = 0.001). Adding 4Kscore improved the prediction of BCR (C-index 0.630-0.660) within GG 3 + 3, but not GG 3 + 4. Conclusions The 4Kscore can help guide the clinical decision whether additional risk assessment-such as confirmatory biopsy-is needed to decide between active surveillance versus curative therapy. Evidence that the panel could influence management in biopsy GG 3 + 4 is less strong and requires further investigation.
|
|
| 11. |
- Chesnut, G. T., et al.
(författare)
-
Estimating patient health in prostate cancer treatment counseling
- 2023
-
Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 26, s. 271-275
-
Tidskriftsartikel (refereegranskat)abstract
- Background We assessed the concordance among urologists' judgment of health quartiles for patients with localized prostate cancer, and compared the life expectancy (LE) and ensuing treatment recommendations when following National Comprehensive Cancer Network (NCCN) guidelines based on actuarial life tables versus the Kent model, a validated LE prediction model. Methods NCCN suggests using actuarial life tables and relying on surgeon assessment of patient health to increase (for the best quartile) or decrease (for the worst quartile) LE by 50%. Eleven urologic surgeons allocated quartile of health and recommended treatments for ten patient vignettes. The 10-year survival probability was calculated using the Kent model and compared to the life-table estimate based on health quartile by surgeon consensus. Results Surgeon assessment agreed with the presumed true quartile of health based on a validated model in 41% of cases. For no case did three-quarters of surgeons assign health quartile correctly; in half of cases, <50% of surgeons assigned the correct quartile. The NCCN comorbidity-adjusted LE estimates underestimated risk of death in the best health quartile and overestimated risk of death in the worst health quartile, compared to the Kent model. Patients with LE > 10 years on NCCN estimation were recommended more frequently for surgery (81%) and those with <= 10 years estimated LE were more commonly recommended for radiation (57%) or observation (29%). Conclusions A method based on physician-assessed health quartiles for LE estimation, as suggested by the NCCN guidelines, appears too crude to be used in the treatment counseling of men with localized prostate cancer, as compared to a validated prediction model, such as the Kent model.
|
|
| 12. |
- Cheung, K. H., et al.
(författare)
-
Extending gene ontology in the context of extracellular RNA and vesicle communication
- 2016
-
Ingår i: Journal of Biomedical Semantics. - : Springer Science and Business Media LLC. - 2041-1480. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: To address the lack of standard terminology to describe extracellular RNA (exRNA) data/metadata, we have launched an inter-community effort to extend the Gene Ontology (GO) with subcellular structure concepts relevant to the exRNA domain. By extending GO in this manner, the exRNA data/metadata will be more easily annotated and queried because it will be based on a shared set of terms and relationships relevant to extracellular research. Methods: By following a consensus-building process, we have worked with several academic societies/consortia, including ERCC, ISEV, and ASEMV, to identify and approve a set of exRNA and extracellular vesicle-related terms and relationships that have been incorporated into GO. In addition, we have initiated an ongoing process of extractions of gene product annotations associated with these terms from Vesiclepedia and ExoCarta, conversion of the extracted annotations to Gene Association File (GAF) format for batch submission to GO, and curation of the submitted annotations by the GO Consortium. As a use case, we have incorporated some of the GO terms into annotations of samples from the exRNA Atlas and implemented a faceted search interface based on such annotations. Results: We have added 7 new terms and modified 9 existing terms (along with their synonyms and relationships) to GO. Additionally, 18,695 unique coding gene products (mRNAs and proteins) and 963 unique non-coding gene products (ncRNAs) which are associated with the terms: "extracellular vesicle", "extracellular exosome", "apoptotic body", and "microvesicle" were extracted from ExoCarta and Vesiclepedia. These annotations are currently being processed for submission to GO. Conclusions: As an inter-community effort, we have made a substantial update to GO in the exRNA context. We have also demonstrated the utility of some of the new GO terms for sample annotation and metadata search.
|
|
| 13. |
|
|
| 14. |
- Perera, M., et al.
(författare)
-
Outcomes of Grade Group 2 and 3 Prostate Cancer on Initial Versus Confirmatory Biopsy: Implications for Active Surveillance
- 2023
-
Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 9:4, s. 662-668
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Active surveillance (AS) is recommended as the preferred treatment for men with low-risk disease. In order to optimize risk stratification and exclude undiagnosed higher-grade disease, most AS protocols recommend a confirmatory biopsy.Objective: We aimed to compare outcomes among men with grade group (GG) 2/3 prostate cancer on initial biopsy with those among men whose disease was initially GG1 but was upgraded to GG2/3 on confirmatory biopsy.Design, setting, and participants: We reviewed patients undergoing radical prostatectomy (RP) in two cohorts: "immediate RP group,"with GG2/3 cancer on diagnostic biopsy, and "AS group,"with GG1 cancer on initial biopsy that was upgraded to GG2/3 on confirmatory biopsy.Outcome measurements and statistical analysis: Probabilities of biochemical recurrence (BCR) and salvage therapy were determined using multivariable Cox regression models with risk adjustment. Risks of adverse pathology at RP were also compared using logistic regression.Results and limitations: The immediate RP group comprised 4009 patients and the AS group comprised 321 patients. The AS group had lower adjusted rates of adverse pathology (27% vs 35%, p = 0.003). BCR rates were lower in the AS group, although this did not reach conventional significance (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.50-1.06, p = 0.10) compared with the immediate RP group. Risk-adjusted 1- and 5yr BCR rates were 4.6% (95% CI 3.0-6.5%) and 10.4% (95% CI 6.9-14%), respectively, for the AS group compared with 6.3% (95% CI 5.6-7.0%) and 20% (95% CI 19-22%), respectively, in the immediate RP group. A nonsignificant association was observed for salvage treatment-free survival favoring the AS group (HR 0.67, 95% CI 0.42, 1.06, p = 0.087).Conclusions: We found that men with GG1 cancer who were upgraded on confirmatory biopsy tend to have less aggressive disease than men with the same grade found at initial biopsy. These results must be confirmed in larger series before recommendations can
|
|
| 15. |
- Austria, M., et al.
(författare)
-
Patient Perceptions of a Decision Support Tool for Men with Localized Prostate Cancer
- 2023
-
Ingår i: Medical Decision Making Policy & Practice. - : SAGE Publications. - 2381-4683. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose. To evaluate patient perceptions of a Web-based decision aid for the treatment of localized prostate cancer. Methods. We assessed patient perceptions of a multicomponent, Web-based decision aid with a preference elicitation/values clarification exercise using adaptive conjoint analysis, the generation of a summary report, and provision of information about localized prostate cancer treatment options. Using a think-aloud approach, we conducted 21 cognitive interviews with prostate cancer patients presented with the decision aid prior to seeing their urologist. Thematic content analysis was used to examine patient perceptions of the tool's components and content prior to engaging in shared decision making with their clinician. Results. Five themes were identified: 1) patients had some negative emotional reactions to the tool, pointing out what they perceived to be unnecessarily negative framing and language used; 2) patients were forced to stop and think about preferences while going through the tool and found this deliberation to be useful; 3) patients were confused by the tool; 4) patients tried to discern the intent of the conjoint analysis questions; and 5) there was a disconnect between patients' negative reactions while using the tool and a contrasting general satisfaction with the final "values profile" created by the tool. Conclusions. Studies are needed to explore the disconnect between patients' expressing negative reactions while going through some components of decision aids but satisfaction with the final output. In particular, we hypothesize that this effect might be explained by cognitive biases such as choice-supportive bias, hindsight bias, and the "IKEA effect." This is one of the first projects to elicit patient reactions while they were completing a decision aid, and we recommend further similar, qualitative postprocess evaluation studies.
|
|
| 16. |
- Friberg, A. S., et al.
(författare)
-
Impact of previous depression on the risk of suicide among prostate cancer patients
- 2023
-
Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 62:1, s. 89-99
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrior studies of suicide risk among prostate cancer patients are conflicting. We compared the risk of suicide in prostate cancer patients to cancer-free men including adjustment for clinical stage, socioeconomic position, somatic comorbidity, and previous depression.Materials and methodsA cohort of 37,527 men diagnosed with prostate cancer in Denmark during 1998-2011 was identified in the Danish Prostate Cancer Registry (DaPCaR) and compared with 357,384 cancer-free men matched by age at the time of diagnosis. The primary outcome was death from suicide. Data were analyzed using cumulative incidence functions and multivariable Cox regression models.ResultsAmong prostate cancer patients, 3813 had a previous depression, defined as filed antidepressant prescription within three years before diagnosis. In the study period, 108 prostate cancer patients were registered with suicide as the cause of death, hereof 26 with previous depression. There was no difference in the cumulative incidence of suicide between prostate cancer patients and cancer-free men. There was no effect modification of previous depression on the risk of suicide (p = .12). The hazard ratio (HR) for suicide varied with time since diagnosis. A sensitivity analysis showed that the risk of suicide was highest within the first year of diagnosis where prostate cancer patients had a 1.70-fold increased hazard compared with cancer-free men (95% CI, 1.11-2.59). Men with prostate cancer and previous depression had a three-fold increased hazard for suicide compared with prostate cancer patients without a history of depression (HR 2.84, 95% CI, 1.82-4.45).ConclusionThe absolute risk of suicide is low following a prostate cancer diagnosis. Time since diagnosis and a history of depression was associated with the highest risk of suicide. Healthcare professionals should be aware of an increased risk of suicide among men with previous depression, especially in the immediate aftermath of the diagnosis.
|
|
| 17. |
|
|
| 18. |
- Lynch, K. A., et al.
(författare)
-
Suggestions for modifications to the Female Sexual Function Index based on cognitive interviews with sexual and gender minority individuals and cisgender, heterosexual persons
- 2023
-
Ingår i: Journal of Sexual Medicine. - 1743-6095 .- 1743-6109. ; 20:6, s. 871-877
-
Tidskriftsartikel (refereegranskat)abstract
- Background Patient-reported outcome measures for sexual health were often designed for research studies that included only heterosexual, partnered, and cisgender participants; as such, they may have limited applicability for clinical use among sexual and gender minority (SGM) individuals or those without a partner.Aim We aimed to conduct cognitive interviews with SGM persons and heterosexual women to determine the readability, comprehension, and applicability of questionnaire items to assess sexual function among diverse sexual and gender identities.Methods We conducted 4 rounds of cognitive interviews with 52 participants (28 SGM; 24 cisgender, heterosexual) who provided feedback on the comprehension and wording of questionnaire items and response scales. We used items from the Female Sexual Function Index (FSFI) and focused on establishing content validity of a modified measure. Participants made recommendations for changes to the questionnaire, which was iteratively revised between interview rounds. Two independent coders analyzed the transcripts using structural coding based on 5 predefined codes: satisfaction with item, specificity/language change needed, missing/suggested item, patient definitions of concepts, and confusion with item.Outcomes Content validity.Results After 3 rounds of cognitive interviews and revisions to the questionnaire, participants found the final version acceptable and understandable, thereby reaching thematic saturation and establishing content validity of the modified FSFI. Modifications included the following: replacing all instances of "sexual stimulation" and "intercourse" with "sexual activity (alone or with a partner)," broadening the definition of "vaginal penetration" beyond penile-vaginal penetration, and adding skip logic to include the option "no sexual activity." Participants identified missing concepts important to their sexual health, such as use of an external lubricant.Clinical Implications The FSFI and similar questionnaires need to be adapted to broader clinical practice populations such that all persons' experiences are accurately reflected and assessed, ensuring that sexual health needs can be met more inclusively.Strength and Limitations A strength of the study was using cognitive interviews engaging patient perspectives, which is considered the gold standard for establishing content validity. One limitation is that participants included predominantly White and highly educated women.Conclusion Feedback from interviews supports modifying FSFI items and further psychometric testing, and future studies should evaluate the measure among racially and educationally diverse groups.
|
|
| 19. |
|
|
| 20. |
- Perera, M., et al.
(författare)
-
Oncologic Outcomes of Total Length Gleason Pattern 4 on Biopsy in Men with Grade Group 2 Prostate Cancer
- 2022
-
Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 208:2, s. 309-316
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Gleason Score 7 prostate cancer comprises a wide spectrum of disease risk, and precise substratification is paramount. Our group previously demonstrated that the total length of Gleason pattern (GP) 4 is a better predictor than %GP4 for adverse pathological outcomes at radical prostatectomy. We aimed to determine the association of GP4 length on prostate biopsy with post-prostatectomy oncologic outcomes. Materials and Methods: We compared 4 GP4 quantification methods-including maximum %GP4 in any single core, overall %GP4, total length GP4 (mm) across all cores and length GP4 (mm) in the highest volume core-for prediction of biochemical recurrence-free survival after radical prostatectomy using multivariable Cox proportional hazards regression. Results: A total of 457 men with grade group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy. The 3-year biochemical recurrence-free survival probability was 85% (95% CI 81-88). On multivariable analysis, all 4 GP4 quantification methods were associated with biochemical recurrence-maximum % GP4 (HR=1.30; 95% CI 1.07-1.59; p=0.009), overall %GP4 (HR=1.61; 95% CI 1.21-2.15; p=0.001), total length GP4 (HR=2.48; 95% CI 1.36-4.52; p=0.003) and length GP4 in highest core (HR=1.32; 95% CI 1.11-1.57; p=0.001). However, we were unable to identify differences between methods of quantification with a relatively low event rate. Conclusions: These findings support further studies on GP4 quantification in addition to the ratio of GP3 and GP4 to classify prostate cancer risk. Research should also be conducted on whether GP4 quantification could provide a surrogate endpoint for disease progression for trials in active surveillance.
|
|
| 21. |
- Sheikh, A., et al.
(författare)
-
Enterotoxigenic Escherichia coli Degrades the Host MUC2 Mucin Barrier To Facilitate Critical Pathogen-Enterocyte Interactions in Human Small Intestine
- 2022
-
Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 90:2
-
Tidskriftsartikel (refereegranskat)abstract
- Enterotoxigenic Escherichia coli (ETEC) isolates are genetically diverse pathological variants of E. coli defined by the production of heat-labile (LT) and/or heat-stable (ST) toxins. ETEC strains are estimated to cause hundreds of millions of cases of diarrheal illness annually. However, it is not clear that all strains are equally equipped to cause disease, and asymptomatic colonization with ETEC is common in low- to middle-income regions lacking basic sanitation and clean water where ETEC are ubiquitous. Recent molecular epidemiology studies have revealed a significant association between strains that produce EatA, a secreted autotransporter protein, and the development of symptomatic infection. Here, we demonstrate that LT stimulates production of MUC2 mucin by goblet cells in human small intestine, enhancing the protective barrier between pathogens and enterocytes. In contrast, using explants of human small intestine as well as small intestinal enteroids, we show that EatA counters this host defense by engaging and degrading the MUC2 mucin barrier to promote bacterial access to target enterocytes and ultimately toxin delivery, suggesting that EatA plays a crucial role in the molecular pathogenesis of ETEC. These findings may inform novel approaches to prevention of acute diarrheal illness as well as the sequelae associated with ETEC and other pathogens that rely on EatA and similar proteases for efficient interaction with their human hosts. © 2022 American Society for Microbiology. All rights reserved.
|
|
| 22. |
- Austria, M. D., et al.
(författare)
-
Sexual and Gender Minority Persons' Perception of the Female Sexual Function Index
- 2021
-
Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6095. ; 18:12, s. 2020-2027
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patient-reported outcome instruments to assess sexual functioning typically assume that patients are heterosexual and have a single sexual partner, thus they may have limited applicability for sexual and gender minority (SGM) populations as well as for nonpartnered individuals or those with multiple partners. Aim: To explore the perceptions of SGM persons regarding the Female Sexual Function Index (FSFI), a commonly used sexual functioning questionnaire. Methods: We conducted 2 rounds of cognitive interviews with 27 SGM persons with and without a cancer diagnosis. Interviews were audio-recorded and transcribed. Two researchers independently coded the transcripts using inductive thematic analysis to identify major themes. Outcomes: Themes identified via qualitative analysis. Results: Cognitive debriefing with the participants provided critical insights about the way we ask questions about sexual functioning in the oncology clinic. Three overarching themes arose from the data: (i) Certain aspects of the questionnaire were felt to unnecessarily medicalize sexuality; (ii) FSFI domains were perceived to represent a narrow and heteronormative experience of sexuality focused on penile-vaginal intercourse; (iii) Questionnaire domains emphasizing sexual "performance" were perceived as male-oriented. Clinical implications: Questionnaires such as the FSFI that were developed in research studies with specific eligibility criteria need to be adapted to the broader population seen in clinical practice. Strengths & Limitations: Strengths of the study include purposive sampling of SGM persons through LGBTQ networks. Our sample included individuals of different sexual orientations, gender identities, marital status, and cancer histories. However, a limitation is that the the majority of the sample was white and college-educated. Other limitations of the study include the potential sampling bias of self-selected participants with a particular interest in the study questions. Conclusion: The findings provide important evidence for the development of a more inclusive sexual function measure, moving away from the traditional heteronormative, cisnormative approach to measuring sexual function. Copyright (C) 2021, International Society of Sexual Medicine. Published by Elsevier Inc. All rights reserved.
|
|
| 23. |
- Fong, L. G., et al.
(författare)
-
Prelamin A and lamin A appear to be dispensable in the nuclear lamina
- 2006
-
Ingår i: J Clin Invest. ; 116:3, s. 743-752
-
Tidskriftsartikel (refereegranskat)abstract
- Lamin A and lamin C, both products of Lmna, are key components of the nuclear lamina. In the mouse, a deficiency in both lamin A and lamin C leads to slow growth, muscle weakness, and death by 6 weeks of age. Fibroblasts deficient in lamins A and C contain misshapen and structurally weakened nuclei, and emerin is mislocalized away from the nuclear envelope. The physiologic rationale for the existence of the 2 different Lmna products lamin A and lamin C is unclear, although several reports have suggested that lamin A may have particularly important functions, for example in the targeting of emerin and lamin C to the nuclear envelope. Here we report the development of lamin C-only mice (Lmna(LCO/LCO)), which produce lamin C but no lamin A or prelamin A (the precursor to lamin A). Lmna(LCO/LCO) mice were entirely healthy, and Lmna(LCO/LCO) cells displayed normal emerin targeting and exhibited only very minimal alterations in nuclear shape and nuclear deformability. Thus, at least in the mouse, prelamin A and lamin A appear to be dispensable. Nevertheless, an accumulation of farnesyl-prelamin A (as occurs with a deficiency in the prelamin A processing enzyme Zmpste24) caused dramatically misshapen nuclei and progeria-like disease phenotypes. The apparent dispensability of prelamin A suggested that lamin A-related progeroid syndromes might be treated with impunity by reducing prelamin A synthesis. Remarkably, the presence of a single Lmna(LCO) allele eliminated the nuclear shape abnormalities and progeria-like disease phenotypes in Zmpste24-/- mice. Moreover, treating Zmpste24-/- cells with a prelamin A-specific antisense oligonucleotide reduced prelamin A levels and significantly reduced the frequency of misshapen nuclei. These studies suggest a new therapeutic strategy for treating progeria and other lamin A diseases.
|
|
| 24. |
- Gupta, A., et al.
(författare)
-
A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer Screening in Rotterdam, Netherlands
- 2010
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 103:5, s. 708-714
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA. METHODS: The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (>= 3 ngml(-1)), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy. RESULTS: The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), P<0.001, and high-grade cancer (Gleason >= 7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P 0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less. CONCLUSIONS: Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies. British Journal of Cancer (2010) 103, 708-714. doi:10.1038/sj.bjc.6605815 www.bjcancer.com Published online 27 July 2010 (C) 2010 Cancer Research UK
|
|
| 25. |
- Bjartell, Anders, et al.
(författare)
-
Association of cysteine-rich secretory protein 3 and beta-microseminoprotein with outcome after radical prostatectomy
- 2007
-
Ingår i: Clinical Cancer Research. - 1078-0432. ; 13:14, s. 4130-4138
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: It has been suggested that cysteine-rich secretory protein 3 (CRISP-3) and p-microseminoprotein (MSP) are associated with outcome in prostate cancer. We investigated whether these markers are related to biochemical recurrence and whether addition of the markers improves prediction of recurring disease. Experimental Design: Tissue microarrays of radical prostatectomy specimens were analyzed for CRISP-3 and MSP by immunohistochemistry. Associations between marker positivity and postprostatectomy biochemical recurrence [prostate-specific antigen (PSA) > 0.2 ng/mL with a confirmatory level] were evaluated by univariate and multivariable Cox proportional hazards regression. Multivariable analyses controlled for preoperative PSA and pathologic stage and grade. Results: Among 945 patients, 224 had recurrence. Median follow-up for survivors was 6.0 years. Patients positive for CRISP-3 had smaller recurrence-free probabilities, whereas MSP-positive patients had larger recurrence-free probabilities. On univariate analysis, the hazard ratio for patients positive versus negative for CRISP-3 was 1.53 (P =0.010) and for MSP was 0.63 (P = 0.004). On multivariable analysis, both CRISP-3 (P = 0.007) and MSP (P = 0.002) were associated with recurrence. The hazard ratio among CRISP-3-positive/MSP-negative patients compared with CRISP-3-negative/MSP-positive patients was 2.38. Adding CRISP-3 to a base model that included PSA and pathologic stage and grade did not enhance the prediction of recurrence, but adding MSP increased the concordance index minimally from 0.778 to 0.781. Conclusion: We report evidence that CRISP-3 and MSP are independent predictors of recurrence after radical prostatectomy for localized prostate cancer. However, addition of the markers does not importantly improve the performance of existing predictive models. Further research should aim to elucidate the functions of CRISP-3 and MSP in prostate cancer cells.
|
|
| 26. |
- Carlsson, Sigrid, 1982, et al.
(författare)
-
Shared Medical Appointments for Prostate Cancer Active Surveillance Followup Visits
- 2021
-
Ingår i: Urology Practice. - : Ovid Technologies (Wolters Kluwer Health). - 2352-0779. ; 8:5, s. 541-545
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: To accommodate for the rapidly increasing patient volume and followup visits of men with prostate cancer on active surveillance (AS), we carried out a quality improvement project to secure high-quality care and enhance patient experience. Methods: We proposed an innovative clinic systems redesign-"shared medical appointments" (SMAs)-in which multiple patients were seen in a group format at the same time by the health care team led by a urologist leading the Institution's AS program. Results: We piloted four SMAs during July-November 2019. Running the SMAs was feasible and improved the contact time for each patient while at the same time being time and resource efficient for the health care providers and using the standard billing processes. The group dynamic was open and pleasant. The majority of patients rated their overall experience with SMA as excellent. Almost all patients responded that they were likely or very likely to attend another SMA in the future. All patients said that they would either definitely or probably recommend this visit type to a friend of family member with prostate cancer. Most patients rated their overall satisfaction with the SMA as extremely high. Conclusions: Utilizing SMAs for AS followup visits was feasible and acceptable. Our promising findings suggest that SMAs can ensure high-quality patient care. Well-controlled studies comparing SMAs to individual usual care visits should be conducted with end points including knowledge, patient and staff satisfaction, anxiety and quality-of-life outcomes, AS adherence, process measures and resource utilization.
|
|
| 27. |
- Gallagher, David J., et al.
(författare)
-
Susceptibility Loci Associated with Prostate Cancer Progression and Mortality
- 2010
-
Ingår i: Clinical Cancer Research. - 1078-0432. ; 16:10, s. 2819-2832
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Prostate cancer is a heterogenous disease with a variable natural history that is not accurately predicted by currently used prognostic tools. Experimental Design: We genotyped 798 prostate cancer cases of Ashkenazi Jewish ancestry treated for localized prostate cancer between June 1988 and December 2007. Blood samples were prospectively collected and de-identified before being genotyped and matched to clinical data. The survival analysis was adjusted for Gleason score and prostate-specific antigen. We investigated associations between 29 single nucleotide polymorphisms (SNP) and biochemical recurrence, castration-resistant metastasis, and prostate cancer-specific survival. Subsequently, we did an independent analysis using a high-resolution panel of 13 SNPs. Results: On univariate analysis, two SNPs were associated (P < 0.05) with biochemical recurrence, three SNPs were associated with clinical metastases, and one SNP was associated with prostate cancer specific mortality. Applying a Bonferroni correction (P < 0.0017), one association with biochemical recurrence (P = 0.0007) was significant. Three SNPs showed associations on multivariable analysis, although not after correcting for multiple testing. The secondary analysis identified an additional association with prostate cancer-specific mortality in KLK3 (P < 0.0005 by both univariate and multivariable analysis). Conclusions: We identified associations between prostate cancer susceptibility SNPs and clinical end points. The rs61752561 in KLK3 and rs2735839 in the KLK2-KLK3 intergenic region were strongly associated with prostate cancer-specific survival, and rs10486567 in the 7JAZF1 gene were associated with biochemical recurrence. A larger study will be required to independently validate these findings and determine the role of these SNPs in prognostic models. Clin Cancer Res; 16(10); 2819-32. (C) 2010 AACR.
|
|
| 28. |
- Lilja, Hans, et al.
(författare)
-
Prediction of Significant Prostate Cancer Diagnosed 20 to 30 Years Later With a Single Measure of Prostate-Specific Antigen at or Before Age 50
- 2011
-
Ingår i: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 117:6, s. 1210-1219
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported that a single prostate-specific antigen (PSA) measured at ages 44-50 was highly predictive of subsequent prostate cancer diagnosis in an unscreened population. Here we report an additional 7 years of follow-up. This provides replication using an independent data set and allows estimates of the association between early PSA and subsequent advanced cancer (clinical stage >= T3 or metastases at diagnosis). METHODS: Blood was collected from 21,277 men in a Swedish city (74% participation rate) during 1974-1986 at ages 33-50. Through 2006, prostate cancer was diagnosed in 1408 participants; we measured PSA in archived plasma for 1312 of these cases (93%) and for 3728 controls. RESULTS: At a median follow-up of 23 years, baseline PSA was strongly associated with subsequent prostate cancer (area under the curve, 0.72; 95% Cl, 0.70-0.74; for advanced cancer, 0.75; 95% Cl, 0.72-0.78). Associations between PSA and prostate cancer were virtually identical for the initial and replication data sets, with 81% of advanced cases (95% Cl, 77%-86%) found in men with PSA above the median (0.63 ng/mL at ages 44-50). CONCLUSIONS: A single PSA at or before age 50 predicts advanced prostate cancer diagnosed up to 30 years later. Use of early PSA to stratify risk would allow a large group of low-risk men to be screened less often but increase frequency of testing on a more limited number of high-risk men. This is likely to improve the ratio of benefit to harm for screening. Cancer 2011;117:1210-9. (C) 2010 American Cancer Society
|
|
| 29. |
- Liu, Yao, et al.
(författare)
-
Changes in TDP-43 expression in development, aging, and in the neurofilament light protein knockout mouse
- 2015
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 36:2, s. 1151-1159
-
Tidskriftsartikel (refereegranskat)abstract
- The transactive response DNA-binding protein 43 (TDP-43) has been identified as a neurofilament light (NF-L) messenger RNA (mRNA)-binding protein. Abnormally increased levels of TDP-43 are detected in patients with amyotrophic lateral sclerosis and a downregulation of NF-L mRNA. However, links between NF-L and TDP-43 expressions are unclear. In this study, we investigated whether the deficiency of NF-L protein can result in alterations in TDP-43 localization or protein expression and whether this is altered with aging. There was a significant increase in TDP-43 protein levels in the cortex and lumbar spinal cord in 12-month-old NF-L knockout (NF-L KO) mice, compared with wild-type (WT) C57BL/6 mice. However, there was no difference in either the phosphorylation of TDP-43 between WT and NF-L KO mice or the abnormal mislocalization of TDP-43 to the cytoplasm in NF-L KO animals. Our findings suggest that NF-L protein or mRNA may negatively affect the expression of TDP-43 in the central nervous system. However, altered phosphorylation of TDP-43 may be more highly associated with aging than the levels of TDP-43 expression.
|
|
| 30. |
- Malm, Johan, et al.
(författare)
-
Long-term prediction of prostate cancer diagnosis and death using PSA and obesity related anthropometrics at early middle age: Data from the malmö preventive project
- 2018
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:5, s. 5778-5785
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. Results: After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. Materials and Methods: In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Conclusions: Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multivariable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics. © Assel et al.
|
|
| 31. |
- Pellegrino, Francesco, et al.
(författare)
-
Predictive value of kallikrein forms and β-microseminoprotein in blood from patients with evidence of detectable levels of PSA after radical prostatectomy
- 2023
-
Ingår i: World Journal of Urology. - 1433-8726. ; 41, s. 1489-1495
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine whether β-microseminoprotein or any of the kallikrein forms in blood-free, total or intact PSA or total hK2-predict metastasis in patients with evidence of detectable levels of PSA in blood after radical prostatectomy.METHOD: We determined marker concentrations in blood from 173 men treated with radical prostatectomy and evidence of detectable levels of PSA in the blood (PSA ≥ 0.05) after surgery between 2014 and 2015 and at least 1 year after any adjuvant therapy. We used Cox regression to determine whether any marker was associated with metastasis using both univariate and multivariable models that included standard clinical predictors.RESULTS: Overall, 42 patients had metastasis, with a median follow-up of 67 months among patients without an event. The levels of intact and free PSA and free-to-total PSA ratio were significantly associated with metastasis. Discrimination was highest for free PSA (c-index: 0.645) and free-to-total PSA ratio (0.625). Only free-to-total PSA ratio remained associated with overall metastasis (either regional or distant) after including standard clinical predictors (p = 0.025) and increased discrimination from 0.686 to 0.697. Similar results were found using distant metastasis as an outcome (p = 0.011; c-index increased from 0.658 to 0.723).CONCLUSION: Our results provide evidence that free-to-total PSA ratio can risk stratifying patients with evidence of detectable levels of PSA in blood after RP. Further research is warranted on the biology of prostate cancer markers in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. Our findings on the free-to-total ratio for predicting adverse oncologic outcomes need to be validated in other cohorts.
|
|
| 32. |
|
|
| 33. |
- Steuber, Thomas, et al.
(författare)
-
Comparison of free and total forms of serum human kallikrein 2 and prostate-specific antigen for prediction of locally advanced and recurrent prostate cancer
- 2007
-
Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 53:2, s. 233-240
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We evaluated the association of total and free forms of serum human kallikrein 2 (hK2) and prostate-specific antigen (PSA) with prostate cancers of unfavorable prognosis. Methods: We retrospectively measured total PSA (tPSA), free PSA (fPSA), and total hK2 (thK2) in preoperative serum samples from 867 men [and assessed free hK2 (fhK2) measured in 577 of these men] treated with radical prostatectomy for clinically localized prostate cancer. Associations between biomarker concentrations and extracapsular extension, seminal vesicle invasion, and biochemical recurrence (BCR) were evaluated. A subset of patients with PSA <= 10 mu g/L, the group most commonly seen in clinical practice in the US, was analyzed. Results: thK2 was the strongest predictor of extracapsular extension and seminal vesicle invasion (areas under the ROC curve [AUC], 0.662 and 0.719, respectively), followed by tPSA (AUC, 0.654 and 0.663). All biomarkers were significant predictors of BCR. hK2 forms, but not PSA forms, remained highly significant for predicting BCR in the low-PSA group. Combining tPSA, fPSA, and thK2 in a multivariable model improved prediction compared with any biomarker used individually (AUC, 0.711, 0.755, and 0.752 for this combination predicting extracapsular extension, seminal vesicle invasion, and BCR, respectively; P < 0.001 for all). Conclusions: Increased concentrations of hK2 in the blood are significantly associated with unfavorable features of prostate cancer, and thK2 is predictive of locally advanced and recurrent cancer in patients with PSA <= <= 10 mu g/L. Independent of tPSA and fPSA, hK2 predicts unfavorable prognosis. (c) 2007 American Association for Clinical Chemistry
|
|
| 34. |
- Steuber, Thomas, et al.
(författare)
-
Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator receptor in serum improve selection of patients for prostate cancer biopsy
- 2007
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 120:7, s. 1499-1504
-
Tidskriftsartikel (refereegranskat)abstract
- Clinicians currently use simple cut-points, such as serum prostate-specific antigen (PSA) >= 4 ng/ml, to decide whether to recommend further work-up for prostate cancer (PCa). As an alternative strategy, we evaluated multivariable models giving probabilities of a PCa diagnosis based on PSA and several circulating novel biomarkers. We measured total PSA, free PSA (fPSA), fPSA subfractions (single-chain fPSA-I and multichain fPSA-N), total human glandular kallikrein 2 (hK2) and full-length and cleaved forms of soluble urokinase plasminogen activator receptor (suPAR) in pretreatment serum from 355 men referred for prostate biopsy. Age and total PSA were combined in a "base" regression model to predict biopsy outcome. We then compared this base model to models supplemented by various combinations of circulating markers, using concordance index (AUC) to measure diagnostic discrimination. PCa prediction was significantly enhanced by models supplemented by measurements of suPAR fragments and fPSA isoforms. Addition of these markers improved bootstrap-corrected AUC from 0.611 for a cut-point and 0.706 for the base model to 0.754 for the full model (p = 0.005). This improved diagnostic accuracy was also seen in subanalysis of patients with PSA 2-9.99 ng/ml and normal findings on DRE (0.652 vs. 0.715, p = 0.039). In this setting, hK2 did not add diagnostic information. Measurements of individual forms of suPAR and PSA isoforms contributed significantly to discrimination of men with PCa from those with no evidence of malignancy. (c) 2007 Wiley-Liss, Inc.
|
|
| 35. |
- Steuber, T, et al.
(författare)
-
Risk assessment for biochemical recurrence prior to radical prostatectomy: significant enhancement contributed by human glandular kallikrein 2 (hk2) and free prostate specific antigen (PSA) in men with moderate PSA-elevation in serum
- 2006
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 118:5, s. 1234-1240
-
Tidskriftsartikel (refereegranskat)abstract
- Most models to predict biochemical recurrence (BCR) of prostate cancer use pretreatment serum prostate-specific antigen (PSA), clinical stage and prostate biopsy Gleason grade. We investigated whether human glandular kallikrein 2 (hK2) and free prostate-specific antigen (fPSA) measured in pretreatment serum enhance prediction. We retrospectively measured total PSA (tPSA), fPSA and hK2 in preoperative serum samples from 461 men with localized prostate cancer treated with radical prostatectomy between 1999 and 2001. We developed a regression model to predict BCR using preoperative tPSA, clinical stage and biopsy Gleason grade. We then compared the predictive accuracy of this "base" model with a model with fPSA and hK2 as additional predictors. BCR was observed in 90 patients (20%), including 48 patients with a pretreatment tPSA <= 14 ng/ml (13%), and 28 patients (10%) With a pretreatment tPSA <= 10 ng/ml. Overall, the predictive accuracy of the base model (bootstrap-corrected concordance index of 0.813) was not improved after the addition of fPSA or hK2 (0.818). However, for men with moderate tPSA-elevation (tPSA <= 10 ng/ml), addition of fPSA and hK2 data increased predictive accuracy (from a base model concordance index of 0.756-0.815, p = 0.005). The improvement in accuracy was not sensitive to the threshold for "moderately elevated" PSA. For patients with a moderate tPSA-elevation (tPSA <= 10 ng/ml), which closely corresponds to concurrent disease demographics, BCR-prediction was enhanced when fPSA and hK2 were added to the conventional model. Measurements of fPSA and hK2 improve on our ability to counsel patients prior to treatment as to their risk of BCR. (c) 2005 Wiley-Liss, Inc.
|
|
| 36. |
- Ulmert, David, et al.
(författare)
-
Long-term prediction of prostate cancer: Prostate-specific antigen (PSA) velocity is predictive but does not improve the predictive accuracy of a single PSA measurement 15 years or more before cancer diagnosis in a large, representative, unscreened population
- 2008
-
Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 26:6, s. 835-841
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose We tested whether total prostate-specific antigen velocity (tPSAv) improves accuracy of a model using PSA level to predict long-term risk of prostate cancer diagnosis. Methods During 1974 to 1986 in a preventive medicine study in Sweden, 5,722 men aged <= 50 gave two blood samples about 6 years apart. We measured free (fPSA) and total PSA (tPSA) in archived plasma samples from 4,907 participants. Prostate cancer was subsequently diagnosed in 443 (9%) men. Cox proportional hazards regression was used to evaluate tPSA and tPSAv as predictors of prostate cancer. Predictive accuracy was assessed by the concordance index. Results The median time from second blood draw to cancer diagnosis was 16 years; median follow-up for men without prostate cancer was 21 years. In univariate models, tPSA level at second assessment and tPSAv between first and second assessments were associated with prostate cancer (both P < .001). tPSAv was highly correlated with tPSA level (r = 0.93). Twenty-year probabilities of cancer for men at 50th, 90th, and 95th percentile of tPSA and tPSAv were 10.6%, 17.1%, and 21.2% for tPSA, and 9.1%, 11.8%, and 14.1% for tPSAv, respectively. The concordance index for tPSA level was 0.771. Adding tPSAv, fPSA, % fPSA or velocities of fPSA and % fPSA did not importantly increase accuracy of tPSA to predict prostate cancer. Results were unchanged if the analysis was restricted to patients with advanced cancer at diagnosis. Conclusion Although PSA velocity is significantly increased in men with prostate cancer up to two decades before diagnosis, it does not aid long-term prediction of prostate cancer.
|
|
| 37. |
- Ulmert, David, et al.
(författare)
-
Prostate-specific antigen at or before age 50 as a predictor of advanced prostate cancer diagnosed up to 25 years later: A case-control study
- 2008
-
Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Based on a large, representative unscreened cohort from Malmo, Sweden, we have recently reported that a single prostate-specific antigen (PSA) measurement at or before age 50 is a strong predictor of prostate cancer occurring up to 25 years subsequently. We aimed to determine whether this association holds for advanced cancers, defined as clinical stage T3 or higher, or skeletal metastasis at the time of the cancer diagnosis. Methods: In 1974-1986 blood samples were obtained from a cohort of 21,277 men aged up to 50. Through 1999, 498 men were diagnosed with prostate cancer, and of these 161 had locally advanced or metastatic prostate cancers. Three controls, matched for age and date of venipuncture, were selected for each case. Conditional logistic regression was used to test associations between molecular markers and advanced cancer. Results: Median time from venipuncture to diagnosis was 17 years. Levels of all PSA forms and hK2 were associated with case status. Total PSA was a strong and statistically significant predictor of subsequent advanced cancer ( area under the curve 0.791; p < 0.0005). Two-thirds of the advanced cancer cases occurred in men with the top 20% of PSA levels (0.9 ng/ml or higher). Conclusion: A single PSA test taken at or before age 50 is a very strong predictor of advanced prostate cancer diagnosed up to 25 years later. This suggests the possibility of using an early PSA test to risk-stratify patients so that men at highest risk are the focus of the most intensive screening efforts.
|
|
| 38. |
- Vickers, A. J., et al.
(författare)
-
A comparison of brief versus explicit descriptors for verbal rating scales: interrupted time series design
- 2023
-
Ingår i: Health and Quality of Life Outcomes. - 1477-7525. ; 21:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundVerbal rating scales (VRS) are widely used in patient-reported outcome (PRO) measures. At our institution, patients complete an online instrument using VRSs with a five-point brief response scale to assess symptoms as part of routine follow-up after ambulatory cancer surgery. We received feedback from patients that the brief VRS descriptors such as "mild" or "somewhat" were vague. We added explicit descriptors to our VRSs, for instance, "Mild: I can generally ignore my pain" for pain severity or "Somewhat: I can do some things okay, but most of my daily activities are harder because of fatigue" for fatigue interference. We then compared responses before and after this change was made.MethodsThe symptoms investigated were pain, fatigue and nausea. Our hypothesis was that the explicit descriptors would reduce overall variance. We therefore compared the coefficient of variation of scores and tested the association between symptoms scores and known predictors thereof. We also compared time to completion between questionnaires with and without the additional descriptors.ResultsA total of 17,500 patients undergoing 21,497 operations were assigned questionnaires in the period before the descriptors were added; allowing for a short transition period, 1,417 patients having 1436 operations were assigned questionnaires with the additional descriptors. Symptom scores were about 10% lower with the additional descriptors but the coefficient of variation was slightly higher. Moreover, the only statistically significant difference between groups for association with a known predictor favored the item without the additional language for nausea severity (p = 0.004). Total completion time was longer when the instrument included the additional descriptors, particularly the first and second time that the questionnaire was completed.ConclusionsAdding descriptors to a VRS of post-operative symptoms did not improve scale properties in patients undergoing ambulatory cancer surgery. We have removed the additional descriptors from our tool. We recommend further comparative psychometric research using data from PROs collected as part of routine clinical care.
|
|
| 39. |
- Vickers, Andrew J., et al.
(författare)
-
Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen
- 2014
-
Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA. Methods: Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162). Results: If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality. Conclusions: Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening.
|
|
| 40. |
- Vickers, Andrew J., et al.
(författare)
-
The predictive value of prostate cancer biomarkers depends on age and time to diagnosis: Towards a biologically-based screening strategy
- 2007
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:10, s. 2212-2217
-
Tidskriftsartikel (refereegranskat)abstract
- Both benign and malignant prostate diseases elevate total prostate-specific antigen (tPSA), and the incidence of benign disease increases markedly with age. There is evidence, however, that free-to-total PSA ratio (%fPSA) and human kallikrein 2 (hK2) more closely reflect the malignant process. We tested the hypothesis that tPSA levels are more strongly predictive of cancer in younger when compared to older men, whereas %fPSA and hK2 are more strongly predictive in men tested closer to diagnosis. The study included 13,676 men age >= 44 in Sweden, where PSA screening was uncommon during the study period. fPSA, tPSA and hK2 were measured in archived plasma collected during 1974-1986 in 501 men subsequently diagnosed with prostate cancer up to 1999 and in 1,292 matched controls. The predictive value of tPSA was lower in older men (p = 0.003) but was not strongly affected by time to diagnosis (p = 0.3); the predictive value of hK2 was higher closer to diagnosis (p < 0.0005) but was not modified by age (p = 0.7). A model including tPSA, fPSA and hK2 was superior (p = 0.02) to tPSA alone in older (AUC 0.819 vs. 0.794), but not in younger men (0.758 vs. 0.759). Total PSA can be used as a single marker at early middle age to predict long-term risk of prostate cancer and thus to determine intensity of subsequent screening. In contrast, %fPSA and hK2 add important predictive value in older men and much closer to diagnosis. Strategies for prostate cancer screening should be based on thorough understanding of the interaction of kallikreinrelated biomarkers with prostate pathobiology.
|
|
| 41. |
|
|
