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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.

PURPOSE To assess whether ultrasonographic (US) findings associate with clinical findings in severe knee osteoarthritis (OA). Association of US findings with side-of-knee pain and inter-reader agreement of knee US were also evaluated. METHODS One-hundred-two patients (in total 123 knees) with severe knee OA were recruited for this cross-sectional study. US was performed by a single observer, and on 53 knees by two independent observers to assess inter-reader reliability. Preoperative clinical data was available for 69 knees. Cutoff values were applied to dichotomize US and clinical findings. The Chi-square test, Mann-Whitney test, and prevalence- and bias-adjusted kappa (PABAK) were applied for statistical analyses. RESULTS Seven of 99 associations tested were statistically significant. Associations were observed between range of flexion and lateral femoral (P = .009) and tibial (P = .001) osteophytes, mediolateral instability and damage to the lateral femoral cartilage (P = .014) and damage to the lateral meniscus (P = .031), and alignment and damage to the lateral femoral cartilage (P

Prostate MRI has high NPV (around 90%) for clinically significant prostate cancer (csPCa, ISUP grade group ≥ 2)1. However, clinicians are still faced with significant uncertainty when considering whether to avoid or to proceed to systematic biopsies in a man with negative MRI (nMRI). When making such an informed decision, information on the risk of subsequent csPCa diagnosis after nMRI in respect to risk of csPCa in general population may be beneficial. Hence, our objective was to compare incidence rate (IR) of csPCa and overdiagnosis rate (diagnosis of ISUP grade group 1 cancer, isPCa) after nMRI (PI-RADS 1-2) to outcomes in general population, and to assess the value of age and PSA-density in stratification. We utilized institutional and national registries to retrospectively identify 1,685 50-79-year-old PCa-free men who underwent a primary nMRI at our institution, of whom 906 men had PSA-D < 0.15 ng/ml/cm3. We compared the IR of csPCa and overdiagnosis rate in relation to general population (n=230,246) during follow-up (up to four years) under clinical routine since December 2015 (PIRADS v2 era). We calculated age-standardized IR ratios (IRR) of csPCa and odds ratios (OR) of overdiagnosis with 95% confidence intervals (95% CI) as age-pooled and among 10-year interval groups (50-59, 60-69 and 70-79 years). Follow-up times in general population cohort, nMRI cohort, and nMRI and low PSA-D cohort were 885,792, 3,363, and 1,821 years and IRs of csPCa were 406, 2,201, and 989 per 100,000 person years. In reference to general population, IRR of csPCa in nMRI cohort was 4.2 (95% CI 3.3-5.4) which reduced to 1.8 (95% CI 1.1-2.9) if PSA-D was < 0.15 ng/ml/cm3. ORs of isPCa were 3.0 (95% CI 2.0-4.6) and 4.6 (95% CI 2.2-9.5), respectively. IRRs of csPCa of 50-59, 60-69 and 70-79-year-old men were 14.1 (95% CI 10.5-25.4), 3.2 (95% CI 2.1-4.6) and 3.4 (95% CI 1.6-3.9). Limitations of this study include retrospective and registry-based design. In conclusion, the risk of subsequent csPCa after nMRI in young men is significant, when compared to population risk. However, with advancing age, these risks converge. For a subgroup of men with PSA-D < 0.15 ng/ml/cm3, the relative risk of csPCa is low in all age groups and comparable to population risk. At the same time, the risk of overdiagnosis after nMRI is substantially higher than in general population. In light of our results, elderly men with nMRI and men at all age groups with nMRI and PSA-D < 0.15 ng/ml/cm3 could be considered candidates for follow-up instead of systematic biopsy. References: 1. Sathianathen NJ, Omer A, Harriss E, et al. Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in the Detection of Clinically Significant Prostate Cancer in the Prostate Imaging Reporting and Data System Era: A Systematic Review and Meta-analysis. Eur Urol. 2020;78(3):402-414. doi:10.1016/j.eururo.2020.03.048 Citation Format: Juho Pylväläinen, Jaakko Hoffström, Anu Kenttämies, Anssi Auvinen, Tuomas Mirtti, Antti Rannikko. Incidence of clinically significant prostate cancer after negative prostate MRI - comparison to general population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2234.

Prostate cancer (PCa) diagnostics are shifting towards multi-parametric magnetic resonance imaging (MRI) combined with targeted biopsies. However, some 10% of clinically significant PCa (csPCa) is missed with current MRI sequences. Evidence on biological differences between MRI visible and invisible csPCa is scarce. Our aim was to find out, whether MRI invisible lesions harbor more indolent characteristics compared to visible csPCa lesions, and to identify transcript markers of MRI visibility. Methods: A retrospective cohort of 45 radical prostatectomy-treated men with csPCa, including 30 with MRI visible lesions, 15 with MRI invisible lesions and additional 19 benign controls. Apparent diffusion coefficient (ADC) values of the invisible lesions were measured based on their topographical locations in histological slides. The histological slides were checked for histological subtypes of PCa and the prostate epithelium and stroma surface area were measured using machine learning. mRNA was analyzed using Nanostring nCounter platform. First, hierarchical clustering of transcript copy counts was performed. Next, differentially expressed genes (DEGs) between study groups were analyzed and Reactome pathway analysis was performed to identify genes and pathways responsible for MRI visibility. Random forest models (RFMs) were trained to predict MRI visibility using DEGs, and genes in MSK-IMPACT, Decipher, Oncotype DX and Prolaris. RFMs were also trained to predict metastatic and lethal PCa using DEGs. Results: MRI negative lesions remained invisible upon radiologist re-evaluation. Clinicopathological characteristics did not explain MRI invisibility, while ADC values were higher in invisible lesions than visible ones. Hierarchical clustering did not separate visible and invisible lesions, while benign samples formed a cluster. We identified a set of 10 and 52 DEGs and 65 enriched pathways between visible and invisible specimens. RFMs performed well in predicting MRI visibility for our 10- and 52-gene DEG sets (AUC = 0.92), for transcripts in Decipher, Oncotype DX, Prolaris (AUC = 0.69-0.86) and MSK-IMPACT (AUC = 0.93). RFMs based on 52- and 10-DEG sets showed independent value in predicting metastatic (AUC = 0.67 and 0.65) and lethal disease (AUC = 0.70 and 0.72) and the samples with predicted poor outcomes based on RFMs had significantly worse survival (p < 0.0001). Conclusions: MRI visibility is net result of many genes and might be linked to various biological processes. Invisible lesions harbor a less aggressive transcript signature than visible csPCa and might be considered for more conservative management. Further research is required to validate these findings on protein level and to find histological correlates. Promising markers altered in currently MRI invisible csPCa could be used to improve MRI sequences. Citation Format: Timo-Pekka K. Lehto, Carolin Stürenberg, Juho Pylväläinen, Kevin Sandeman, Anu Kenttämies, Stig Nordling, Jing Tang, Tuomas Mirtti, Antti Rannikko. Gene expression in multi-parametric MRI visible and invisible prostate cancers predicts progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5171.

Objectives To identify the prognostic factors of prostate cancer death among patients enrolled in a Finnish prostate cancer screening trial. Methods Data on TNM stage, Gleason score, serum prostate-specific antigen at diagnosis, comorbidity and primary treatment were collected from medical records, as well as date and cause of death from Statistics Finland. Four prognostic risk groups were defined based on TNM stage, Gleason score and prostate-specific antigen at diagnosis. Hazard ratios and their 95% confidence intervals for prostate cancer death were calculated using Cox regression and competing-risk analysis with follow up from randomization. The differences in the effects of prognostic factors were assessed using interaction terms. Results The 15-year survival was significantly lower among cases in the control arm compared with the screening arm (0.90 vs 0.92). However, the survival advantage was limited to screen-detected cases (0.94 vs 0.91 in cases detected outside screening). The prognostic risk group was the strongest factor predicting survival in the control arm, but weaker in screen-detected cases. Advanced disease was associated with substantially poorer outcome in cases detected outside screening than in screen-detected disease. Primary treatment had a similar effect in all groups. Comorbidity had a small prognostic effect in the control arm only. Conclusions Prognostic factors had a different effect on the outcome of cases detected through screening as those diagnosed otherwise. A high diagnostic prostate-specific antigen and advanced disease carried a poor prognosis, especially among the cases detected outside screening, even when lead-time was eliminated. This shows that the screening resulted in earlier treatment among the cases in the screening arm.

The purpose of this study was to assess the effectiveness of the ultrasonography (US) on detecting osteoarthritis of the knee, and compare US and radiographic findings to intraoperative total knee arthroplasty (TKA) findings. Fifty-seven late-stage osteoarthritic knees undergoing TKA were evaluated with US and radiography. Standard knee US assessing femoral cartilage damage, osteophytes, effusion, synovitis, and meniscal extrusion was performed. On radiographs, osteophytes, joint space narrowing, and Kellgren-Lawrence grade were evaluated. Corresponding intra-operative findings were assessed during TKA as the gold standard. On the damage of the medial femoral condyle cartilage, the sensitivity of US was high (92%), whereas on the lateral condyle and sulcus area, sensitivities were 58% and 46%, respectively. On osteophytes, the detection rate of the US was remarkable especially on the medial side yielding sensitivities of 90–95%. The sensitivities for detecting effusion and synovitis were also excellent (97%). US detection rate of femoral cartilage damage was in concordance with the radiographic joint space narrowing. For the detection of osteophytes, US provided superior results to radiography particularly on the medial side. In conclusion, US can reliably assess the late-stage OA changes of the knee especially on the medial side of the knee joint.