Publications by authors named "Tuomas P Kilpeläinen"

21 Publications

  • Page 1 of 1

A three-feature prediction model for metastasis-free survival after surgery of localized clear cell renal cell carcinoma.

Sci Rep 2021 Apr 21;11(1):8650. Epub 2021 Apr 21.

Department of Oncology and Radiotherapy, Fican West Cancer Centre, University of Turku and Turku University Hospital, Hämeentie 11, Post Box 52, 20521, Turku, Finland.

After surgery of localized renal cell carcinoma, over 20% of the patients will develop distant metastases. Our aim was to develop an easy-to-use prognostic model for predicting metastasis-free survival after radical or partial nephrectomy of localized clear cell RCC. Model training was performed on 196 patients. Right-censored metastasis-free survival was analysed using LASSO-regularized Cox regression, which identified three key prediction features. The model was validated in an external cohort of 714 patients. 55 (28%) and 134 (19%) patients developed distant metastases during the median postoperative follow-up of 6.3 years (interquartile range 3.4-8.6) and 5.4 years (4.0-7.6) in the training and validation cohort, respectively. Patients were stratified into clinically meaningful risk categories using only three features: tumor size, tumor grade and microvascular invasion, and a representative nomogram and a visual prediction surface were constructed using these features in Cox proportional hazards model. Concordance indices in the training and validation cohorts were 0.755 ± 0.029 and 0.836 ± 0.015 for our novel model, which were comparable to the C-indices of the original Leibovich prediction model (0.734 ± 0.035 and 0.848 ± 0.017, respectively). Thus, the presented model retains high accuracy while requiring only three features that are routinely collected and widely available.
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http://dx.doi.org/10.1038/s41598-021-88177-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060273PMC
April 2021

Expected impact of MRI-related interreader variability on ProScreen prostate cancer screening trial: a pre-trial validation study.

Cancer Imaging 2020 Oct 9;20(1):72. Epub 2020 Oct 9.

Department of Urology, University of Helsinki and Helsinki University Hospital, PL900, 00029 HUS, Helsinki, Finland.

Background: The aim of this study is to investigate the potential impact of prostate magnetic resonance imaging (MRI) -related interreader variability on a population-based randomized prostate cancer screening trial (ProScreen).

Methods: From January 2014 to January 2018, 100 men aged 50-63 years with clinical suspicion of prostate cancer (PCa) in Helsinki University Hospital underwent MRI. Nine radiologists individually reviewed the pseudonymized MRI scans of all 100 men in two ProScreen trial centers. All 100 men were biopsied according to a histological composite variable comprising radical prostatectomy histology (N = 38) or biopsy result within 1 year from the imaging (N = 62). Fleiss' kappa (κ) was used to estimate the combined agreement between all individual radiologists. Sample data were subsequently extrapolated to 1000-men subgroups of the ProScreen cohort.

Results: Altogether 89% men of the 100-men sample were diagnosed with PCa within a median of 2.4 years of follow-up. Clinically significant PCa (csPCa) was identified in 76% men. For all PCa, mean sensitivity was 79% (SD ±10%, range 62-96%), and mean specificity 60% (SD ±22%, range 27-82%). For csPCa (Gleason Grade 2-5) MRI was equally sensitive (mean 82%, SD ±9%, range 67-97%) but less specific (mean 47%, SD ±20%, range 21-75%). Interreader agreement for any lesion was fair (κ 0.40) and for PI-RADS 4-5 lesions it was moderate (κ 0.60). Upon extrapolating these data, the average sensitivity and specificity to a screening positive subgroup of 1000 men from ProScreen with a 30% prevalence of csPCa, 639 would be biopsied. Of these, 244 men would be true positive, and 395 false positive. Moreover, 361 men would not be referred to biopsy and among these, 56 csPCas would be missed. The variation among the radiologists was broad as the least sensitive radiologist would have twice as many men biopsied and almost three times more men would undergo unnecessary biopsies. Although the most sensitive radiologist would miss only 2.6% of csPCa (false negatives), the least sensitive radiologist would miss every third.

Conclusions: Interreader agreement was fair to moderate. The role of MRI in the ongoing ProScreen trial is crucial and has a substantial impact on the screening process.
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http://dx.doi.org/10.1186/s40644-020-00351-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547469PMC
October 2020

Serum tumour associated trypsin inhibitor, as a biomarker for survival in renal cell carcinoma.

Scand J Urol 2020 Oct 4;54(5):413-419. Epub 2020 Aug 4.

Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Objective: Tumour associated trypsin inhibitor (TATI) is a peptide that is a marker for several tumours. TATI may also behave as an acute phase reactant in severe inflammatory disease. Overexpression of TATI predicts an unfavourable outcome for many cancers. This study aimed to evaluate the prognostic value of pre- and postoperative concentration of TATI in serum (S-TATI) of patients with renal cell carcinoma (RCC).

Materials And Methods: S-TATI was determined by time resolved immunofluorometric assay in preoperative and postoperative samples that were collected from 132 RCC patients, who underwent partial or complete nephrectomy in Helsinki University Hospital from May 2005 to July 2010.

Results: Preoperative S-TATI was significantly associated with tumour stage, lymph-node involvement, metastatic stage, Chronic Kidney Disease Stage (CKD grade), and preoperative C-reactive protein level ( < 0.05). Postoperative S-TATI was significantly associated only with CKD grade ( < 0.001). Multivariate Cox regression analysis of postoperative S-TATI, as a continuous variable, was an independent prognostic factor for overall survival (HR = 1.01, 95% CI = 1.00-1.01,  = 0.03) and cancer-specific survival (CSS) (HR = 1.01, 95% CI = 1.00-1.02,  = 0.004).

Conclusions: Our data suggest that elevated postoperative S-TATI may be associated with adverse prognosis in RCC patients.
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http://dx.doi.org/10.1080/21681805.2020.1798501DOI Listing
October 2020

Prostate MRI added to CAPRA, MSKCC and Partin cancer nomograms significantly enhances the prediction of adverse findings and biochemical recurrence after radical prostatectomy.

PLoS One 2020 9;15(7):e0235779. Epub 2020 Jul 9.

Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Background: To determine the added value of preoperative prostate multiparametric MRI (mpMRI) supplementary to clinical variables and their role in predicting post prostatectomy adverse findings and biochemically recurrent cancer (BCR).

Methods: All consecutive patients treated at HUS Helsinki University Hospital with robot assisted radical prostatectomy (RALP) between 2014 and 2015 were included in the analysis. The mpMRI data, clinical variables, histopathological characteristics, and follow-up information were collected. Study end-points were adverse RALP findings: extraprostatic extension, seminal vesicle invasion, lymph node involvement, and BCR. The Memorial Sloan Kettering Cancer Center (MSKCC) nomogram, Cancer of the Prostate Risk Assessment (CAPRA) score and the Partin score were combined with any adverse findings at mpMRI. Predictive accuracy for adverse RALP findings by the regression models was estimated before and after the addition of MRI results. Logistic regression, area under curve (AUC), decision curve analyses, Kaplan-Meier survival curves and Cox proportional hazard models were used.

Results: Preoperative mpMRI data from 387 patients were available for analysis. Clinical variables alone, MSKCC nomogram or Partin tables were outperformed by models with mpMRI for the prediction of any adverse finding at RP. AUC for clinical parameters versus clinical parameters and mpMRI variables were 0.77 versus 0.82 for any adverse finding. For MSKCC nomogram versus MSKCC nomogram and mpMRI variables the AUCs were 0.71 and 0.78 for any adverse finding. For Partin tables versus Partin tables and mpMRI variables the AUCs were 0.62 and 0.73 for any adverse finding. In survival analysis, mpMRI-projected adverse RP findings stratify CAPRA and MSKCC high-risk patients into groups with distinct probability for BCR.

Conclusions: Preoperative mpMRI improves the predictive value of commonly used clinical variables for pathological stage at RP and time to BCR. mpMRI is available for risk stratification prebiopsy, and should be considered as additional source of information to the standard predictive nomograms.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235779PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347171PMC
September 2020

Associations of PTEN and ERG with Magnetic Resonance Imaging Visibility and Assessment of Non-organ-confined Pathology and Biochemical Recurrence After Radical Prostatectomy.

Eur Urol Focus 2020 Jun 30. Epub 2020 Jun 30.

Research Program in Systems Oncology, University of Helsinki, Helsinki, Finland; Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Diagnosing clinically significant prostate cancer (PCa) is challenging, but may be facilitated by biomarkers and multiparametric magnetic resonance imaging (MRI).

Objective: To determine the association between biomarkers phosphatase and tensin homolog (PTEN) and ETS-related gene (ERG) with visible and invisible PCa lesions in MRI, and to predict biochemical recurrence (BCR) and non-organ-confined (non-OC) PCa by integrating clinical, MRI, and biomarker-related data.

Design, Setting, And Participants: A retrospective analysis of a population-based cohort of men with PCa, who underwent preoperative MRI followed by radical prostatectomy (RP) during 2014-2015 in Helsinki University Hospital (n = 346), was conducted. A tissue microarray corresponding to the MRI-visible and MRI-invisible lesions in RP specimens was constructed and stained for PTEN and ERG.

Outcome Measurements And Statistical Analysis: Associations of PTEN and ERG with MRI-visible and MRI-invisible lesions were examined (Pearson's χ test), and predictions of non-OC disease together with clinical and MRI parameters were determined (area under the receiver operating characteristic curve and logistic regression analyses). BCR prediction was analyzed by Kaplan-Meier and Cox proportional hazard analyses.

Results And Limitations: Patients with MRI-invisible lesions (n = 35) had less PTEN loss and ERG-positive expression compared with patients (n = 90) with MRI-visible lesions (17.2% vs 43.3% [p = 0.006]; 8.6% vs 20.0% [p = 0.125]). Patients with invisible lesions had better, but not statistically significantly improved, BCR-free survival probability in Kaplan-Meier analyses (p = 0.055). Rates of BCR (5.7% vs 21.1%; p = 0.039), extraprostatic extension (11.4% vs 44.6%; p < 0.001), seminal vesicle invasion (0% vs 21.1%; p = 0.003), and lymph node metastasis (0% vs 12.2%; p = 0.033) differed between the groups in favor of patients with MRI-invisible lesions. Biomarkers had no independent role in predicting non-OC disease or BCR. The short follow-up period was a limitation.

Conclusions: PTEN loss, BCR, and non-OC RP findings were more often encountered with MRI-visible lesions.

Patient Summary: Magnetic resonance imaging (MRI) of the prostate misses some cancer lesions. MRI-invisible lesions seem to be less aggressive than MRI-visible lesions.
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http://dx.doi.org/10.1016/j.euf.2020.06.016DOI Listing
June 2020

Patients' education level and treatment modality for prostate cancer in the Finnish Randomized Study of Screening for Prostate Cancer.

Eur J Cancer 2020 05 28;130:204-210. Epub 2020 Mar 28.

Faculty of Social Sciences (Health Sciences), Tampere University, Tampere, Finland.

Background: In prostate cancer (PCa), lower education level is associated with less screening, more advanced stage at diagnosis and worse survival. The aim of this study was to estimate the association between education level and treatment modality and subsequently survival.

Methods: The 9255 men diagnosed with PCa in the Finnish Randomized Study of Screening for Prostate Cancer were included. Cancer stage, comorbidity, education level and primary treatment modality were extracted from the patient records, the Finnish Cancer Registry, Statistics Finland and the National Institute of Health and Welfare, and these covariates were used in logistic regression (treatment selection) and Cox regression (survival analysis).

Results: In high-risk cancers, men with tertiary education were more likely to be treated with radical prostatectomy (odds ratio [OR] = 1.76; 95% confidence interval [CI] = 1.27-2.44) than men with primary education. Men with secondary (OR = 0.57; 95% CI = 0.38-0.84) or tertiary (OR = 0.42; 95% CI = 0.29-0.60) education were managed less frequently with mere hormonal therapy. In locally advanced cases, tertiary education was associated with more curatively aimed therapies and less hormonal therapy (OR for radical prostatectomy = 2.34; 95% CI = 1.49-3.66; OR for radiotherapy = 1.42; 95% CI = 1.09-1.85; OR for hormonal therapy = 0.45; 95% CI = 0.33-0.60). The hazard ratio for PCa death was lower in men with secondary (0.81; 95% CI = 0.69-0.95) and tertiary (0.75; 95% CI = 0.65-0.87) education than in the patients with primary education.

Conclusions: When controlled for the cancer risk group, comorbidity and patient's age, low education level is independently associated with less curatively aimed treatment in men with high-risk or locally advanced PCa and subsequently worse prognosis.
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http://dx.doi.org/10.1016/j.ejca.2020.02.045DOI Listing
May 2020

Randomized Trials Show a Consistent Benefit of Radical Prostatectomy on Mortality Outcomes.

J Urol 2019 12 3;202(6):1106-1108. Epub 2019 Jul 3.

Departments of Urology and Public Health,.

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http://dx.doi.org/10.1097/JU.0000000000000423DOI Listing
December 2019

Decision Aids for Prostate Cancer Screening Choice: A Systematic Review and Meta-analysis.

JAMA Intern Med 2019 Aug;179(8):1072-1082

Department of Urology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Importance: US guidelines recommend that physicians engage in shared decision-making with men considering prostate cancer screening.

Objective: To estimate the association of decision aids with decisional outcomes in prostate cancer screening.

Data Sources: MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL were searched from inception through June 19, 2018.

Study Selection: Randomized trials comparing decision aids for prostate cancer screening with usual care.

Data Extraction And Synthesis: Independent duplicate assessment of eligibility and risk of bias, rating of quality of the decision aids, random-effects meta-analysis, and Grading of Recommendations, Assessment, Development and Evaluations rating of the quality of evidence.

Main Outcomes And Measures: Knowledge, decisional conflict, screening discussion, and screening choice.

Results: Of 19 eligible trials (12 781 men), 9 adequately concealed allocation and 8 blinded outcome assessment. Of 12 decision aids with available information, only 4 reported the likelihood of a true-negative test result, and 3 presented the likelihood of false-negative test results or the next step if the screening test result was negative. Decision aids are possibly associated with improvement in knowledge (risk ratio, 1.38; 95% CI, 1.09-1.73; I2 = 67%; risk difference, 12.1; low quality), are probably associated with a small decrease in decisional conflict (mean difference on a 100-point scale, -4.19; 95% CI, -7.06 to -1.33; I2 = 75%; moderate quality), and are possibly not associated with whether physicians and patients discuss prostate cancer screening (risk ratio, 1.12; 95% CI, 0.90-1.39; I2 = 60%; low quality) or with men's decision to undergo prostate cancer screening (risk ratio, 0.95; 95% CI, 0.88-1.03; I2 = 36%; low quality).

Conclusions And Relevance: The results of this study provide moderate-quality evidence that decision aids compared with usual care are associated with a small decrease in decisional conflict and low-quality evidence that they are associated with an increase in knowledge but not with whether physicians and patients discussed prostate cancer screening or with screening choice. Results suggest that further progress in facilitating effective shared decision-making may require decision aids that not only provide education to patients but are specifically targeted to promote shared decision-making in the patient-physician encounter.
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http://dx.doi.org/10.1001/jamainternmed.2019.0763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593633PMC
August 2019

A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer.

Eur Urol 2019 07 26;76(1):43-51. Epub 2019 Feb 26.

Erasmus Medical Centre, Rotterdam, The Netherlands.

Background: The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality.

Objective: To determine whether PSA screening decreases PCa mortality for up to 16yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended.

Design, Setting, And Participants: This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182160 men, followed up until 2014 (maximum of 16yr), with a predefined core age group of 162389 men (55-69yr), selected from population registry.

Outcome Measurements And Statistical Analysis: The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended.

Results And Limitations: The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72-0.89, p<0.001) at 16yr. The difference in absolute PCa mortality increased from 0.14% at 13yr to 0.18% at 16yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16yr compared with 742 at 13yr. The number needed to diagnose was reduced to 18 from 26 at 13yr. Men with PCa detected during the first round had a higher prevalence of PSA >20ng/ml (9.9% compared with 4.1% in the second round, p<0.001) and higher PCa mortality (hazard ratio=1.86, p<0.001) than those detected subsequently.

Conclusions: Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level.

Patient Summary: In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer.
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http://dx.doi.org/10.1016/j.eururo.2019.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513694PMC
July 2019

Surgery for metastases of renal cell carcinoma: outcome of treatments and preliminary assessment of Leuven-Udine prognostic groups in the targeted therapy era.

Scand J Urol 2018 Oct - Dec;52(5-6):419-426. Epub 2019 Jan 20.

a Department of Urology , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.

Aim: This study was conducted to evaluate the efficacy of surgical treatment for metastases accompanied by modern targeted therapies and to evaluate the performance of the Leuven-Udine (L.U.) prognostic groups model.

Methods: This retrospective analysis included 97 consecutive patients with metastatic renal cell carcinoma (mR.C.C.) who underwent surgery for metastases at Helsinki University Hospital between 2006 and 2017. The endpoints were overall survival (O.S.), cancer-specific survival (C.S.S.), recurrence-free survival (R.F.S.) and interval from diagnosis to oncological treatment.

Results: The median follow-up time was 46 months (interquartile range, I.Q.R. = 24-74). The estimated median O.S. was 67 months (I.Q.R. = 30-130). A radical surgical result at metastasectomy was achieved in 46 of 97 patients (47%). Of those 46 patients, 28 (61%) experienced recurrence after complete metastasectomy. Median R.F.S. after complete metastasectomy was 10 months (I.Q.R. = 3-37). Five-year O.S. was 59% for patients with complete metastasectomy and 44% for patients with non-complete metastasectomy (p = .035). The median interval from diagnosis to the initiation of targeted oncological treatment was 19 months for patients with non-complete metastasectomy and has hitherto not been reached for patients with complete metastasectomy (p = .006). A statistically significant validation of the prognostic value of the L.U. prognostic groups for predicting C.S.S. was not obtained (p = .420).

Conclusions: Metastasectomy is an option for selected patients with mR.C.C. Complete resection should be attempted when feasible. The data failed to support the prognostic significance of the L.U. model in patients with mR.C.C.
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http://dx.doi.org/10.1080/21681805.2018.1553893DOI Listing
August 2019

Bias-corrected estimates of effects of PSA screening decisions on the risk of prostate cancer diagnosis and death: Analysis of the Finnish randomized study of screening for prostate cancer.

Int J Cancer 2019 08 4;145(3):632-638. Epub 2019 Feb 4.

Faculty of Social Sciences/Health Sciences, University of Tampere, Tampere, Finland.

More information is needed about effects of prostate-specific antigen (PSA) screening for informed decision making. The objective of our study is to evaluate the effects of an implemented screening decision on the risk of prostate cancer (PC) diagnosis and PC death. In a randomized trial, 31,867 Finnish men aged 55-67 years were allocated to the screening arm and 48,282 to the control arm during 1996-1999. Two to three screening rounds were offered to the screening arm with a PSA cut-off of 4.0 ng/ml. A counterfactual exclusion method was used to adjust for the effects of screening noncompliance and PSA contamination on risk of PC death and PC incidence by prognostic group at 15 years of follow up. After correcting for noncompliance and contamination, PSA screening led to 32.4 (95% CI 26.4, 38.6) more PC diagnoses per 1,000 men after 15 years and 1.4 (95% CI 0.0, 2.8) fewer PC deaths compared to the control arm. The corresponding results of an intention-to-screen analysis were 16.5 (95% CI 12.3, 20.7) and 0.8 (95% CI 0.5, 2.0), respectively. These results can be used for patient counseling in informed decision making about PC screening. A limitation of the study was the lack of comprehensive data on contamination.
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http://dx.doi.org/10.1002/ijc.32129DOI Listing
August 2019

Evolving Clinical Picture of Renal Cell Carcinoma: A Population-Based Study from Helsinki.

Urol Int 2019 11;102(4):390-398. Epub 2019 Jan 11.

Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: There is a lack of detailed population-based data for renal cell carcinoma (RCC).

Objectives: The study aimed to examine the contemporary changes in the clinical picture and treatment of RCC.

Methods: A total of 1,719 consecutive patients living in the Helsinki metropolitan area with a solid or cystic renal mass (Bosniak 3-4) ≥10 mm were identified. Data from medical records was evaluated for clinical characteristics and treatments in the periods I (2006-2008), II (2009-2011), III (2012-2014), and IV (2015-2016).

Results: The proportions of patients with comorbidities (Charlson index ≥2) and frailty (Eastern Co-operative Oncology Group classification ≥2) increased significantly during the study period. The percentage of clinical stage I patients, cystic tumors and use of needle biopsies increased significantly. Use of observation increased from 9% (I) to 32% (IV; p < 0.001). First-line oncological treatments within 6 months were given to 47% of 262 patients with metastases and -cytoreductive nephrectomy (CN) was delivered to 54% of those patients.

Conclusions: The size of renal tumors continued to decrease, while the percentage of patients with significant comorbidity or frailty increased. Active surveillance emerged as the initial strategy. Tyrosine kinase inhibitors with CN remained the primary option in patients with metastatic RCC.
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http://dx.doi.org/10.1159/000494363DOI Listing
January 2020

Repeat multiparametric MRI in prostate cancer patients on active surveillance.

PLoS One 2017 27;12(12):e0189272. Epub 2017 Dec 27.

Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Introduction: This study was conducted to describe the changes in repeat multiparametric MRI (mpMRI) occurring in prostate cancer (PCa) patients during active surveillance (AS), and to study possible associations between mpMRI-related parameters in predicting prostate biopsy (Bx) Gleason score (GS) upgrading >3+3 and protocol-based treatment change (TC).

Materials And Methods: The study cohort consisted of 76 AS patients with GS 3+3 PCa and at least two consecutive mpMRIs of the prostate performed between 2006-2015. Patients were followed according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol and an additional mpMRI. The primary end points were GS upgrading (GU) (>3+3) in protocol-based Bxs and protocol-based TC.

Results: Out of 76 patients, 53 (69%) had progression (PIRADS upgrade, size increase or new lesion[s]), while 18 (24%) had radiologically stable disease, and 5 (7%) had regression (PIRADS or size decrease, disappearance of lesion[s]) in repeat mpMRIs during AS. PIRADS scores of 4-5 in the initial mpMRI were associated with GU (p = 0.008) and protocol-based TC (p = 0.009). Tumour progression on repeat mpMRIs was associated with TC (p = 0.045) but not with GU (p = 1.00). PIRADS scores of 4-5 predict GU (sensitivity 0.80 [95% confidence interval (CI); 0.51-0.95, specificity 0.62 [95% CI; 0.52-0.77]) with PPV and NPV values of 0.34 (95% CI; 0.21-0.55) and 0.93 (95% CI; 0.80-0.98), respectively.

Conclusion: mpMRI is a useful tool not only to select but also to monitor PCa patients on AS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189272PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5744936PMC
January 2018

Estimate of Opportunistic Prostate Specific Antigen Testing in the Finnish Randomized Study of Screening for Prostate Cancer.

J Urol 2017 07 16;198(1):50-57. Epub 2017 Jan 16.

School of Health Sciences, University of Tampere, Tampere, Finland.

Purpose: Screening for prostate cancer remains controversial, although ERSPC (European Randomized Study of Screening for Prostate Cancer) showed a 21% relative reduction in prostate cancer mortality. The Finnish Randomized Study of Screening for Prostate Cancer, which is the largest component of ERSPC, demonstrated a statistically nonsignificant 16% mortality benefit in a separate analysis. The purpose of this study was to estimate the degree of contamination in the control arm of the Finnish trial.

Materials And Methods: Altogether 48,295 and 31,872 men were randomized to the control and screening arms, respectively. The screening period was 1996 to 2007. The extent of prostate specific antigen testing was analyzed retrospectively using laboratory databases. The incidence of T1c prostate cancer (impalpable prostate cancer detected by elevated prostate specific antigen) was determined from the national Finnish Cancer Registry.

Results: Approximately 1.4% of men had undergone prostate specific antigen testing 1 to 3 years before randomization. By the first 4, 8 and 12 years of followup 18.1%, 47.7% and 62.7% of men in the control arm had undergone prostate specific antigen testing at least once and in the screening arm the proportions were 69.8%, 81.1% and 85.2%, respectively. The cumulative incidence of T1c prostate cancer was 6.1% in the screening arm and 4.5% in the control arm (RR 1.21, 95% CI 1.13-1.30).

Conclusions: A large proportion of men in the control arm had undergone a prostate specific antigen test during the 15-year followup. Contamination is likely to dilute differences in prostate cancer mortality between the arms in the Finnish screening trial.
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http://dx.doi.org/10.1016/j.juro.2017.01.048DOI Listing
July 2017

Prostate Cancer and Socioeconomic Status in the Finnish Randomized Study of Screening for Prostate Cancer.

Am J Epidemiol 2016 11;184(10):720-731

Prostate cancer (PC) screening remains controversial. We investigated whether screening reduces the difference in prostate cancer risk by socioeconomic status (SES). In 1996-2011, a total of 72,139 men from the Finnish Randomized Study of Screening for Prostate Cancer were analyzed. Outcome measures were PC incidence, mortality, and participation in screening. SES indicators were educational level, income, and home ownership status (data obtained from the Statistics Finland registry). The mean duration of follow-up was 12.7 years. Higher SES was associated with a higher incidence of low- to moderate-risk PC but with a lower risk of advanced PC. Higher education was associated with significantly lower PC mortality in both control and screening arms (risk ratio = 0.48-0.69; P < 0.05). Higher income was also associated with lower PC mortality but only in the control arm (risk ratio = 0.45-0.73; P < 0.05). There were no significant differences in SES gradient by arm (Pinteraction = 0.33 and Pinteraction = 0.47 for primary vs. secondary education and primary vs. tertiary education, respectively; Pinteraction = 0.65 and Pinteraction = 0.09 for low vs. intermediate income and low vs. high income, respectively; and Pinteraction = 0.27 among home ownership status strata). Substantial gradients by SES in PC incidence and mortality were observed in the control arm. Higher SES was associated with overdiagnosis of low-risk PC and, conversely, lower risk of incurable PC and lower PC mortality. Special attention should be directed toward recruiting men with low SES to participate in population-based cancer screening.
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http://dx.doi.org/10.1093/aje/kww084DOI Listing
November 2016

Estimating bias in causes of death ascertainment in the Finnish Randomized Study of Screening for Prostate Cancer.

Cancer Epidemiol 2016 Dec 14;45:1-5. Epub 2016 Sep 14.

School of Health Sciences, University of Tampere, FI-33014 Tampere, Finland.

Background: Precise cause of death (CoD) ascertainment is crucial in any cancer screening trial to avoid bias from misclassification due to excessive recording of diagnosed cancer as a CoD in death certificates instead of non-cancer disease that actually caused death. We estimated whether there was bias in CoD determination between screening (SA) and control arms (CA) in a population-based prostate cancer (PCa) screening trial.

Methods: Our trial is the largest component of the European Randomized Study of Screening for Prostate Cancer with more than 80,000 men. Randomly selected deaths in men with PCa (N=442/2568 cases, 17.2%) were reviewed by an independent CoD committee. Median follow-up was 16.8 years in both arms.

Results: Overdiagnosis of PCa was present in the SA as the risk ratio for PCa incidence was 1.19 (95% confidence interval (CI) 1.14-1.24). The hazard ratio (HR) for PCa mortality was 0.94 (95%CI 0.82-1.08) in favor of the SA. Agreement with official CoD registry was 94.6% (κ=0.88) in the SA and 95.4% (κ=0.91) in the CA. Altogether 14 PCa deaths were estimated as false-positive in both arms and exclusion of these resulted in HR 0.92 (95% CI 0.80-1.06).

Conclusions: A small differential misclassification bias in ascertainment of CoD was present, most likely due to attribution bias (overdiagnosis in the SA). Maximum precision in CoD ascertainment can only be achieved with independent review of all deaths in the diseased population. However, this is cumbersome and expensive and may provide little benefit compared to random sampling.
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http://dx.doi.org/10.1016/j.canep.2016.08.022DOI Listing
December 2016

Outcome of surgery for patients with renal cell carcinoma and tumour thrombus in the era of modern targeted therapy.

Scand J Urol 2016 Oct;50(5):380-6

a Department of Urology , Helsinki University Hospital , Helsinki , Finland ;

Objective: This study evaluated the clinical outcome of patients with renal cell carcinoma (RCC) with tumour thrombus (TT) after surgical management.

Materials And Methods: In total, 142 consecutive RCC patients with TT who were operated on in Helsinki University Hospital between 2006 and 2014 were analysed. Eighty-eight (62%) of these patients had been operated on with radical intention and 54 (38%) with cytoreductive intention. A total of 73 patients (51%) received postoperative targeted therapy. The primary endpoint was cancer-specific survival (CSS).

Results: The 5 year CSS for level of involvement of TT in the renal vein, subdiaphragmatic vena cava and supradiaphragmatic vena cava was 60% (81 patients), 43% (52 patients) and 51% (nine patients), respectively (p = .42). The median CSS for lymph-node involvement was 63 months for patients with no lymph-node involvement but 10 months for patients with lymph-node involvement (p < .01). The median CSS for metastasis status was 63 months for patients with no metastases compared with 18 months for patients with metastases (p < .01). Among several factors examined, WHO performance status (p = .04), tumour necrosis (p = .05), presence of distant metastases (p = .04) and tumour histology (p = .05) were associated with CSS in the multivariate analysis.

Conclusions: Operative treatment for RCC with TT is associated with good prognosis when there is no lymph-node involvement or distant metastases.
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http://dx.doi.org/10.1080/21681805.2016.1217558DOI Listing
October 2016

The Finnish prostate cancer screening trial: analyses on the screening failures.

Int J Cancer 2015 May 10;136(10):2437-43. Epub 2014 Nov 10.

Department of Urology, Helsinki University Hospital, FI-00029, Helsinki, Finland.

Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). However, in the Finnish trial, which is the largest component of the ERSPC, no statistically significant mortality reduction was observed. We investigated which had the largest impact on PC deaths in the screening arm: non-participation, interval cancers or PSA threshold. The screening (SA) and control (CA) arms comprised altogether 80,144 men. Men in the SA were screened at four-year intervals and referred to biopsy if the PSA concentration was ≥ 4.0 ng/ml, or 3.0-3.99 ng/ml with a free/total PSA ratio ≤ 16%. The median follow-up was 15.0 years. A counterfactual exclusion method was applied to estimate the effect of three subgroups in the SA: the non-participants, the screen-negative men with PSA ≥ 3.0 ng/ml and a subsequent PC diagnosis, and the men with interval PCs. The absolute risk of PC death was 0.76% in the SA and 0.85% in the CA; the observed hazard ratio (HR) was 0.89 (95% confidence interval (CI) 0.76-1.04). After correcting for non-attendance, the HR was 0.78 (0.64-0.96); predicted effect for a hypothetical PSA threshold of 3.0 ng/ml the HR was 0.88 (0.74-1.04) and after eliminating the effect of interval cancers the HR was 0.88 (0.74-1.04). Non-participating men in the SA had a high risk of PC death and a large impact on PC mortality. A hypothetical lower PSA threshold and elimination of interval cancers would have had a less pronounced effect on the screening impact.
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http://dx.doi.org/10.1002/ijc.29300DOI Listing
May 2015

Prostate cancer mortality in the Finnish randomized screening trial.

J Natl Cancer Inst 2013 May 11;105(10):719-25. Epub 2013 Mar 11.

Department of Urology, University of Tampere and Tampere University Hospital, Tampere, Finland.

Background: Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality.

Methods: A total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0 ng/mL or 3.0 to 3.99 ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided.

Results: PC incidence was 8.8 per 1000 person-years in the SA and 6.6 in the CA (HR = 1.34, 95% confidence interval [CI] = 1.27 to 1.40). The incidence of advanced PC was lower in the SA vs CA arm (1.2 vs 1.6, respectively; HR = 0.73, 95% CI = 0.64 to 0.82; P < .001). For PC mortality, no statistically significant difference was observed between the SA and CA (HR = 0.85, 95% CI = 0.69 to 1.04) (with intention-to-screen analysis). To avoid one PC death, we needed to invite 1199 men to screening and to detect 25 PCs. We observed no difference in all-cause mortality between trial arms.

Conclusions: At 12 years, a relatively conservative screening protocol produced a small, non-statistically significant PC-specific mortality reduction in the Finnish trial, at the cost of moderate overdiagnosis.
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http://dx.doi.org/10.1093/jnci/djt038DOI Listing
May 2013

False-positive screening results in the European randomized study of screening for prostate cancer.

Eur J Cancer 2011 Dec 23;47(18):2698-705. Epub 2011 Jul 23.

Dept. of Urology, Tampere University Hospital and University of Tampere, Finland.

Background: Screening for prostate cancer (PC) with prostate-specific antigen (PSA) has been shown to decrease mortality, but has adverse effects, such as false-positive (FP) screening results. We describe the frequency of FP results and assess their relation to subsequent screening attendance, test results and prostate cancer risk in a large randomized trial.

Materials And Methods: We included data from five centres of the European Randomized Study of Screening for Prostate Cancer, altogether over 61,000 screened men. Men were screened with PSA test at a 2-7 year interval depending on the centre; PSA cut-off was 3.0-4.0 ng/ml. A positive screen with no histologically confirmed PC in biopsy within 1 year was defined as an FP result.

Results: Of the 61,604 men who were screened at least once, 17.8% had one or more FP result(s). Almost 20% of men who participated at all screening rounds had one or more FP result(s). More than half of the men with an FP result had another FP if screened again. Men with FP results had a fourfold risk of PC at subsequent screen (depending on the round, 10.0% versus 2.6-2.7% of men with negative screen, risk ratio 3.8-3.9). The PCs following an FP result were in 92.8% of cases localised and low-grade versus 90.4% following a screen-negative result.

Conclusions: Our results show that FP results are common adverse effects in PC screening, as they affect at least one in six screened men. False-positive men are more prone to be diagnosed with PC but are also likely to have consistently high PSA levels.
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http://dx.doi.org/10.1016/j.ejca.2011.06.055DOI Listing
December 2011

Results of the three rounds of the Finnish Prostate Cancer Screening Trial--the incidence of advanced cancer is decreased by screening.

Int J Cancer 2010 Oct;127(7):1699-705

Department of Urology, Tampere University Hospital and University of Tampere, FIN-33521 Tampere, Finland.

Screening for prostate cancer (PC) remains a controversial issue despite some new evidence on the mortality benefits of PC screening. We conducted a prospective, randomized screening trial in Finland to investigate whether screening decreases PC incidence. Here, we report the incidence results from three screening rounds during a 12-year period. Of the 80,144 men enrolled, 31,866 men were randomized to the screening arm (SA) and invited for screening with prostate-specific antigen test (cut-off 4.0 ng/ml) every 4 years, while the remaining men formed the control arm (CA) that received no interventions. The mean follow-up time for PC incidence in both arms was over 9 years. The incidence rate of PC (including screen-detected and interval cancers as well as cases among nonparticipants) was 9.1 per 1,000 person-years in the SA and 6.2 in the CA, yielding an incidence rate ratio (IRR) 1.5 (95% confidence interval 1.4-1.5). The incidence of advanced PC was 1.1 in the SA and 1.5 in the CA, IRR = 0.7 (0.6-0.8) and the difference emerges after 5-6 years of follow-up. The incidence of localized PC was 7.5 in the SA and 4.6 in the CA, IRR = 1.6 (1.5-1.7). The results from our large population-based trial indicate that screening for PC decreases the incidence of advanced PC. When compared with the CA, the PC detected in the SA there were substantially more often localized, low-grade PCs due to overdiagnosis.
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http://dx.doi.org/10.1002/ijc.25368DOI Listing
October 2010