Risk of Clinically Significant Prostate Cancer after a Nonsuspicious Prostate MRI-A Comparison with the General Population.

BACKGROUND: We compare the risk of clinically significant (csPCa; ISUP Grade Group ≥ 2) and insignificant prostate cancer (isPCa; ISUP Grade Group 1) in men with a nonsuspicious prostate MRI (nMRI; PI-RADS ≤ 2) with the general population, and assess the value of PSA density (PSAD) in stratification. METHODS: In this retrospective population-based cohort study we identified 1,682 50-79-year-old men, who underwent nMRI at HUS (2016-2019). We compared their age-standardized incidence rates (IR) of csPCa and the odds of isPCa to a local age- and sex-matched general population (n = 230,458) during a six-year follow-up. Comparisons were performed by calculating incidence rate ratios (IRR) and ORs with 95% confidence intervals (CI). We repeated the comparison for the 920 men with nMRI and PSAD < 0.15 ng/mL/cm3. RESULTS: Compared with the general population, the IR of csPCa was significantly higher after nMRI [1,852 vs. 552 per 100,000 person-years; IRR 3.4 (95% CI, 2.8-4.1)]. However, the IR was substantially lower if PSAD was low [778 per 100,000 person-years; IRR 1.4 (95% CI, 0.9-2.0)]. ORs for isPCa were 2.4 (95% CI, 1.7-3.5) for all men with nMRI and 5.0 (95% CI, 2.8-9.1) if PSAD was low. CONCLUSIONS: Compared with the general population, the risk of csPCa is not negligible after nMRI. However, men with nMRI and PSAD <0.15 ng/mL/cm3 have worse harm-benefit balance than men in the general population. IMPACT: Prostate biopsies for men with nMRI should be reserved for cases indicated by additional risk stratification. See related In the Spotlight, p. 641.

Histomic and transcriptomic features of MRI-visible and invisible clinically significant prostate cancers are associated with prognosis.

Magnetic resonance imaging (MRI) is increasingly used to triage patients for prostate biopsy. However, 9% to 24% of clinically significant (cs) prostate cancers (PCas) are not visible in MRI. We aimed to identify histomic and transcriptomic determinants of MRI visibility and their association to metastasis, and PCa-specific death (PCSD). We studied 45 radical prostatectomy-treated patients with csPCa (grade group [GG]2-3), including 30 with MRI-visible and 15 with MRI-invisible lesions, and 18 men without PCa. First, histological composition was quantified. Next, transcriptomic profiling was performed using NanoString technology. MRI visibility-associated differentially expressed genes (DEGs) and Reactome pathways were identified. MRI visibility was classified using publicly available genes in MSK-IMPACT and Decipher, Oncotype DX, and Prolaris. Finally, DEGs and clinical parameters were used to classify metastasis and PCSD in an external cohort, which included 76 patients with metastatic GG2-4 PCa, and 84 baseline-matched controls without progression. Luminal area was lower in MRI-visible than invisible lesions and low luminal area was associated with short metastasis-free and PCa-specific survival. We identified 67 DEGs, eight of which were associated with survival. Cell division, inflammation and transcriptional regulation pathways were upregulated in MRI-visible csPCas. Genes in Decipher, Oncotype DX and MSK-IMPACT performed well in classifying MRI visibility (AUC = 0.86-0.94). DEGs improved classification of metastasis (AUC = 0.69) and PCSD (AUC = 0.68) over clinical parameters. Our data reveals that MRI-visible csPCas harbor more aggressive histomic and transcriptomic features than MRI-invisible csPCas. Thus, targeted biopsy of visible lesions may be sufficient for risk stratification in patients with a positive MRI.

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

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.

Association between grayscale sonographic and clinical findings in severe knee osteoarthritis.

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 < .001), lateral tibial osteophytes (P = .037), and damage to the lateral meniscus (P < .001). A strong association was observed between medial-sided pain and same-sided cartilage damage and osteophytes (P < .001). That inter-reader agreement was excellent on the medial side of the knee joint (PABAK = 0.811-0.887). CONCLUSIONS: US findings show a rather poor association with clinical OA findings. Inter-reader agreement of knee US is excellent on the medial side.

Charlson Comorbidity Index Based On Hospital Episode Statistics Performs Adequately In Predicting Mortality, But Its Discriminative Ability Diminishes Over Time.

PURPOSE: To evaluate the performance of Charlson Comorbidity Index (CCI) calculated using hospitalization and medication reimbursement databases in predicting mortality. PATIENTS AND METHODS: Information on hospitalizations was obtained from the national Care Register for Health Care (HILMO) and on medication reimbursements and entitlements for special reimbursements for medications from the Social Insurance Institution for 77,440 men aged 56-71 years at baseline. The subjects were followed up for mortality via Statistics Finland with 20,562 deaths during a 13-year follow-up. RESULTS: Compared to a CCI score of 0, the age-adjusted hazard ratio for all-cause mortality associated with HILMO-based CCI scores of 1, 2 and 3 or more were 2.39 (95% CI 2.29-2.49), 2.96 (95% CI 2.81-3.13) and 6.42 (95% CI 5.95-6.93) at 13 years. The C-statistic was 0.72 at 1, 0.68 at 5 and 0.66 at 13 years, with only minor improvement over age alone (0.10, 0.06 and 0.04 accordingly). Addition of medication data did not improve predictive abilities and medication-based CCI performed poorly on its own. CONCLUSION: The hospitalization-based CCI, as well as that based on both databases, predicts relative mortality adequately, but its discriminative ability diminishes over time. Conditions related to hospitalizations affect survival more than medications.

Ultrasonography of the late-stage knee osteoarthritis prior to total knee arthroplasty: comparison of the ultrasonographic, radiographic and intra-operative findings.

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.

Prognostic factors of prostate cancer mortality in a Finnish randomized screening trial.

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.