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- Li, Weiqiang, et al.
(author)
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Genome-wide Scan Identifies Role for AOX1 in Prostate Cancer Survival
- 2018
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 74:6, s. 710-719
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Journal article (peer-reviewed)abstract
- We performed genome-wide association studies and found single nucleotide polymorphisms (SNPs) at seven independent loci associated with prostate-cancer-specific survival time. Two SNPs replicated in an independent cohort. The SNP rs73055188 at AOX1 is associated with AOX1 gene expression level, which is correlated with biochemical recurrence.
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- Marconi, Lorenzo, et al.
(author)
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External validation of a predictive model of survival after cytoreductive nephrectomy for metastatic renal cell carcinoma
- 2018
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In: World journal of urology. - : Springer. - 0724-4983 .- 1433-8726. ; 36:12, s. 1973-1980
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Journal article (peer-reviewed)abstract
- IntroductionRecent trials have emphasized the importance of a precise patient selection for cytoreductive nephrectomy (CN). In 2013, a nomogram was developed for pre- and postoperative prediction of the probability of death (PoD) after CN in patients with metastatic renal cell carcinoma. To date, the single-institutional nomogram which included mostly patients from the cytokine era has not been externally validated. Our objective is to validate the predictive model in contemporary patients in the targeted therapy era.MethodsMulti-institutional European and North American data from patients who underwent CN between 2006 and 2013 were used for external validation. Variables evaluated included preoperative serum albumin and lactate dehydrogenase levels, intraoperative blood transfusions (yes/no) and postoperative pathologic stage (primary tumour and nodes). In addition, patient characteristics and MSKCC risk factors were collected. Using the original calibration indices and quantiles of the distribution of predictions, Kaplan-Meier estimates and calibration plots of observed versus predicted PoD were calculated. For the preoperative model a decision curve analysis (DCA) was performed.ResultsOf 1108 patients [median OS of 27months (95% CI 24.6-29.4)], 536 and 469 patients had full data for the validation of the pre- and postoperative models, respectively. The AUC for the pre- and postoperative model was 0.68 (95% CI 0.62-0.74) and 0.73 (95% CI 0.68-0.78), respectively. In the DCA the preoperative model performs well within threshold survival probabilities of 20-50%. Most important limitation was the retrospective collection of this external validation dataset.ConclusionsIn this external validation, the pre- and postoperative nomograms predicting PoD following CN were well calibrated. Although performance of the preoperative nomogram was lower than in the internal validation, it retains the ability to predict early death after CN.
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- Sjoberg, Daniel D., et al.
(author)
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Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men
- 2018
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In: European Urology. - : Elsevier BV. - 0302-2838. ; 73:6, s. 941-948
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Journal article (peer-reviewed)abstract
- Background: Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. Objective: To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Design, setting, participants: Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Outcome measurements and statistical analysis: Prostate cancer death (n = 317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Results and limitations: Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0. ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of <7.5%, translating into 1.7% risk of prostate cancer death at 15 yr-a similar estimate to that of a man with a PSA of 1.6. ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. Conclusions: A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Patient summary: Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy.
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| 5. |
- Vickers, Andrew, et al.
(author)
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Value of Intact Prostate Specific Antigen and Human Kallikrein 2 in the 4 Kallikrein Predictive Model : An Individual Patient Data Meta-Analysis
- 2018
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In: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 199:6, s. 1470-1474
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Journal article (peer-reviewed)abstract
- Purpose: The 4 kallikrein panel, commercially available as the 4Kscore®, is a statistical model that has been shown to accurately predict Gleason Grade Group 2 or greater (high grade) cancer on biopsy and the long-term risk of distant prostate cancer metastases. The panel includes 2 novel markers, namely intact prostate specific antigen and hK2. It has been questioned whether these 2 additional markers add discrimination to the clinical predictors of patient age, digital rectal examination and prior biopsy, and the established molecular markers total and free prostate specific antigen. Materials and Methods: We performed an individual patient data meta-analysis of published studies in which the 4 kallikrein panel was measured in men undergoing prostate biopsy. We assess the improvement in discrimination associated with including intact prostate specific antigen and hK2 along with total and free prostate specific antigen in the statistical model. Results: Included in analysis were 14,510 men from a total of 10 studies. The fixed effects meta-analytical estimate of the discrimination of the model without intact prostate specific antigen and hK2 was 0.742 (95% CI 0.727–0.756) compared to 0.813 (95% CI 0.801–0.825) for the full kallikrein model. The 95% CIs did not overlap and the difference in discrimination was highly statistically significant (0.069, 95% CI 0.057–0.080, p <0.0001). Intact prostate specific antigen (increase in discrimination 0.059, 95% CI 0.050–0.069) and hK2 (increase in discrimination 0.024, 95% CI 0.020–0.029, each p <0.0001) added independently to the model. Conclusions: The clinical value of the panel could not be replicated using data readily available to urologists without measuring intact prostate specific antigen and hK2.
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