| 1. |
- Bjartell, Anders, et al.
(författare)
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Association of cysteine-rich secretory protein 3 and beta-microseminoprotein with outcome after radical prostatectomy
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 13:14, s. 4130-4138
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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.
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| 2. |
- Haas, Gabriel P, et al.
(författare)
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Needle biopsies on autopsy prostates: sensitivity of cancer detection based on true prevalence
- 2007
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 99:19, s. 1484-1489
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is difficult to estimate the diagnostic accuracy of biopsy for prostate cancer because men with negative biopsy do not undergo radical prostatectomy and thus have no confirmation of biopsy findings. METHODS: We performed 18-core needle biopsies on autopsy prostates from 164 men who had no history of prostate cancer. Six-core biopsies were taken from each of the mid peripheral zone (MPZ), the lateral peripheral zone (LPZ), and the central zone (CZ). We tested associations between age and tumor characteristics and analyzed the sensitivity of biopsies at each site. All statistical tests were two-sided. RESULTS: Prostate cancer was present in 47 (29%) prostates. Of the 47 cancers detected, 20 were clinically significant according to histologic criteria. Tumor volume was associated with tumor grade (P = .012) and with age (P<.001). The biopsies from the CZ did not detect any cancer that was not present in biopsies of either the MPZ or LPZ. The sensitivity of the biopsies taken from the MPZ and LPZ together (53%, 95% confidence interval [CI] = 38% to 68%) was therefore the same as that of 18-core biopsies and was superior to that of biopsies of the MPZ alone (30%, 95% CI = 17% to 45%) (P = .003). The sensitivities of biopsies from the MPZ for clinically significant and insignificant cancer were 55% (95% CI = 32% to 77%) and 11% (95% CI = 2% to 29%), respectively, compared with 80% (95% CI = 56% to 94%) and 33% (95% CI = 17% to 54%) for those from the MPZ and LPZ combined. CONCLUSIONS: The ability to detect prostate cancer was more related to the biopsy site than to the number of biopsy cores taken. The 12-core biopsies, six cores each from the MPZ and LPZ, were most likely to detect the majority of clinically significant cancers but also detected many insignificant cancers. When the six-core biopsies from the CZ were added, no increase in sensitivity was observed.
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| 3. |
- Lilja, Hans, et al.
(författare)
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Long-term prediction of prostate cancer up to 25 years before diagnosis of prostate cancer using prostate kallikreins measured at age 44 to 50 years.
- 2007
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 25:4, s. 431-436
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Tidskriftsartikel (refereegranskat)abstract
- Purpose We examined whether prostate-specific antigen (PSA) forms and human kallikrein 2 (hK2) measured at age 44 to 50 years predict long-term risk of incident prostate cancer. Methods From 1974 to 1986, 21,277 men age <= 50 years in Malmo, Sweden, enrolled onto a cardiovascular study (74% participation). The rate of PSA screening in this population is low. According to the Swedish Cancer Registry, 498 were later diagnosed with prostate cancer. We measured hK2, free PSA, and total PSA (tPSA) in archived blood plasma from 462 participants later diagnosed with prostate cancer and from 1,222 matched controls. Conditional logistic regression was used to test for association of prostate cancer with hK2 and PSA forms measured at baseline. Results Median delay between venipuncture and prostate cancer diagnosis was 18 years. hK2 and all PSA forms were strongly associated with prostate cancer (all P < .0005). None of the 90 anthropometric, lifestyle, biochemical, and medical history variables measured at baseline was importantly predictive. A tPSA increase of 1 ng/mL was associated with an increase in odds of cancer of 3.69 (95% CI, 2.99 to 4.56); addition of other PSA forms or hK2 did not add to the predictive value of tPSA. tPSA remained predictive for men diagnosed >= 20 years after venipuncture, and the predictive value remained unchanged in an analysis restricted to palpable disease. Conclusion A single PSA test at age 44 to 50 years predicts subsequent clinically diagnosed prostate cancer. This raises the possibility of risk stratification for prostate cancer screening programs.
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| 4. |
- Secin, Fernando P, et al.
(författare)
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Multi-institutional Study of Symptomatic Deep Venous Thrombosis and Pulmonary Embolism in Prostate Cancer Patients Undergoing Laparoscopic or Robot-Assisted Laparoscopic Radical Prostatectomy
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:1, s. 134-145
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The true incidence of symptomatic deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing laparoscopic radical prostatectomy is unknown. Our aim was to determine the incidence of symptomatic DVT and PE and the risk factors for these complications. METHODS: Fourteen surgeons from 13 referral institutions from both Europe and the United States provided retrospective data for all 5951 patients treated with laparoscopic radical prostatectomy (LRP), with or without robotic assistance, since the start of their institution's experience. Symptomatic DVT and PE within 90 d of surgery were regarded as venous thromboembolism (VTE). DVT was diagnosed mostly by Doppler ultrasound or contrast venography and PE by lung ventilation/perfusion scan or chest computed tomography or both. Statistical analysis included evaluation of incidence of symptomatic DVT and PE and risk factors as determined by exact methods and logistic regression. RESULTS: Of 5951 patients in the study, 31 developed symptomatic VTE (0.5%; 95% confidence interval [CI], 0.4%, 0.7%). Among patients with an event, 22 (71%) had DVT only, 4 had PE without identified DVT, and 5 had both. Two patients died of PE. Prior DVT (odds ratio [OR]=13.5; 95%CI, 1.4, 61.3), current tobacco smoking (OR=2.8; 95%CI, 1.0, 7.3), larger prostate volume (OR=1.18; 95%CI, 1.09, 1.28), patient re-exploration (OR=20.6; 95%CI, 6.6, 54.0), longer operative time (OR=1.05; 95%CI, 1.02, 1.09), and longer hospital stay (OR=1.05; 95%CI, 1.01, 1.09) were associated with VTE in univariate analysis. Neoadjuvant therapy, body mass index, surgical experience, surgical approach, pathologic stage, perioperative transfusion, and heparin administration were not significant predictors. CONCLUSIONS: The incidence of symptomatic VTE after LRP is low. These data do not support the administration of prophylactic heparin to all patients undergoing LRP, especially those without risk factors for VTE.
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| 5. |
- Steuber, Thomas, et al.
(författare)
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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
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 53:2, s. 233-240
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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
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| 6. |
- Ulmert, David, et al.
(författare)
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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
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 26:6, s. 835-841
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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.
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| 7. |
- Vickers, Andrew J., et al.
(författare)
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The predictive value of prostate cancer biomarkers depends on age and time to diagnosis: Towards a biologically-based screening strategy
- 2007
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:10, s. 2212-2217
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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.
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