Decreasing trend in prostate cancer with high serum prostate-specific antigen levels detected at first prostate-specific antigen-based population screening in Japan

To clarify the recent trends in prostate-specific antigen （PSA） distribution in men in Japan, we analyzed the PSA distributions of men undergoing PSA-based population screening. We summarized the annual individual data of PSA-based population screening in Kanazawa, Japan, from 2000 to 2011, and analyzed baseline serum PSA values of the participants at the first population screening. Serum PSA distributions were estimated in all participants and those excluding prostate cancer patients according to age. From 2000 to 2011, 19 620 men participated aged 54-69 years old in this screening program. Mean baseline serum PSA level of all participants at the first screening was 2.64 ng m1-1 in 2000, and gradually decreased to approximately 1.30 ng ml-I in 2006. That of participants excluding prostate cancer patients was 1.46 ng m1-1 in 2000, and there was no remarkable change during the study period. The 95t＂ percentiles in the participants excluding prostate cancer patients detected at the first population screening of men aged 54-59, 60-64, and 65-69 years old were 2.90, 3.60, and 4.50 ng m1-1, respectively. After the commencement of population screening, the proportion of prostate cancer patients with high serum PSA levels decreased. However, there were no changes in serum PSA levels in men without prostate cancer. Age-specific PSA reference level of men without prostate cancer in Japan was similar to that in China and Korea.

Overdiagnosis of breast cancer in population screening:does it make breast screening worthless?

The risk of breast cancer(BC) overdiagnosis attributed to mammography screening is an unresolved issue, complicated by heterogeneity in the methodology of quantifying its magnitude, and both political and scientific elements surrounding interpretation of the evidence on this phenomenon. Evidence from randomized trials and also from observational studies shows that mammography screening reduces the risk of BC death; similarly, these studies provide sufficient evidence that overdiagnosis represents a serious harm from population breast screening. For both these outcomes of screening, BC mortality reduction and overdiagnosis, estimates of magnitude vary between studies however overdiagnosis estimates are associated with substantial uncertainty. The trade-off between the benefit and the collective harms of BC screening, including false-positives and overdiagnosis, is more finely balanced than initially recognized, however the snapshot of evidence presented on overdiagnosis does not mean that breast screening is worthless. Future efforts should be directed towards(a) ensuring that any changes in the implementation of BC screening optimize the balance between benefit and harms, including assessing how planned or actual changes modify the risk of overdiagnosis;(b) informing women of all the outcomes that may affect them when they participate in screening using well-crafted and balanced information; and(c) investing in research that will help define and reduce the ensuing overtreatment of screen-detected BC.

Similar fecal immunochemical test results in screening and referral colorectal cancer

AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mLvs 613 ± 368 ng/mL,P = 0.02). Tissue tumor stage (T stage) distribution was dif-ferent between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mLvs 870 ± 258 ng/mL,P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.

Colorectal and interval cancers of the Colorectal Cancer Screening Program in the Basque Country (Spain)

AIM To assess proportions, related conditions and survival of interval cancer(IC).METHODS The programme has a linkage with different clinical databases and cancer registers to allow suitable evaluation. This evaluation involves the detection of ICs after a negative faecal inmunochemical test(FIT), interval cancer FIT(IC-FIT) prior to a subsequent invitation, and the detection of ICs after a positive FIT and confirmatory diagnosis without colorectal cancer(CRC) detected and before the following recommended c o l o n o s c o p y, I C-c o l o n o s c o p y. W e c o n d u c t e d a retrospective observational study analyzing from January 2009 to December 2015 1193602 invited people onto the Programme(participation rate of 68.6%).RESULTS Two thousand five hundred and eighteen cancers were diagnosed through the programme, 18 cases of IC-colonoscopy were found before the recommended follow-up(43542 colonoscopies performed) and 186 IC-FIT were identified before the following invitation of the 769200 negative FITs. There was no statistically significant relation between the predictor variables of ICs with sex, age and deprivation index, but there was relation between location and stage. Additionally, it was observed that there was less risk when the location was distal rather than proximal(OR = 0.28, 95%CI: 0.20-0.40, P < 0.0001), with no statistical significance when the location was in the rectum as opposed to proximal. When comparing the screen-detected cancers(SCs) with ICs, significant differences in survival were found(P < 0.001); being the 5-years survival for SCs 91.6% and IC-FIT 77.8%.CONCLUSION These findings in a Population Based CRC Screening Programme indicate the need of population-based studies that continue analyzing related factors to improve their detection and reducing harm.

Impact of a colorectal cancer screening program implantation on delays and prognosis of non-screening detected colorectal cancer

BACKGROUND The implementation of a colorectal cancer(CRC)screening programme may increase the awareness of Primary Care Physicians,reduce the diagnostic delay in CRC detected outside the scope of the screening programme and thus improve prognosis.AIM To determine the effect of implementation of a CRC screening programme on diagnostic delays and prognosis of CRC detected outside the scope of a screening programme.METHODS We performed a retrospective intervention study with a pre-post design.We identified 322 patients with incident and confirmed CRC in the pre-implantation cohort(June 2014–May 2015)and 285 in the post-implantation cohort(June 2017-May 2018)in the Cancer Registry detected outside the scope of a CRC screening programme.In each patient we calculated the different healthcare diagnostics delays:global,primary and secondary healthcare,referral and colonoscopyrelated delays.In addition,we collected the initial healthcare that evaluated the patient,the home location(urban/rural),and the CRC stage at diagnosis.We determined the two-year survival and we performed a multivariate proportional hazard regression analysis to determine the variables associated with survival.RESULTS We did not detect any differences in the patient or CRC baseline-related variables.A total of 20.1%of patients was detected with metastatic disease.There was a significant increase in direct referral to colonoscopy from primary healthcare(25.5%,35.8%;P=0.04)in the post-implantation cohort.Diagnostic delay was reduced by 24 d(106.64±148.84 days,82.84±109.31 d;P=0.02)due to the reduction in secondary healthcare delay(46.01±111.65 d;29.20±60.83 d;P=0.02).However,we did not find any differences in CRC stage at diagnosis or in two-year survival(70.3%;P=0.9).Variables independently associated with twoyear risk of death were age(Hazard Ratio-HR:1.06,95%CI:1.04-1.07),CRC stage(II HR:2.17,95%CI:1.07-4.40;III HR:3.07,95%CI:1.56-6.08;IV HR:19.22,95%CI:9.86-37.44;unknown HR:9.24,95%CI:4.27-19.99),initial healthcare consultation(secondary HR:2.93,95%CI:1.01-8.55;emergency department HR:2.06,95%CI:0.67-6.34),hospitalization during the diagnostic process(HR:1.67,95%CI:1.17-2.38)and urban residence(HR:1.44,95%CI:1.06-1.98).CONCLUSION Although implementation of a CRC screening programme can reduce diagnostic delays for CRC detected in symptomatic patients,this has no effect on CRC stage or survival.

Prostate-specific antigen-based population screening for prostatecancer： current status in Japan and future perspective in Asia

In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen （PSA） testing remains very low compared with Western countries, and the benefits of population-based screening remain unclear. This review describes the current status of population screening and diagnosis for prostate cancer in Japan and discusses the efficacy of population screening for the Asian population. Since the 1990s, screening systems have been administered by each municipal government in Japan, and decreases in the prostate cancer mortality rate are expected in some regions where the exposure rate to PSA screening has increased markedly. A population-based screening cohort revealed that the proportion of metastatic disease in cancer detected by screening gradually decreased according to the increased exposure rate, and a decreasing trend in the proportion of cancer with high serum PSA levels after population screening was started. The prognosis of the prostate cancer detected by population screening was demonstrated to be more favorable than those diagnosed outside of the population screening. Recent results in screening cohorts demonstrated the efficacy of PSA. These recent evidences regarding population-based screening in Japan may contribute to establishing the optimal prostate cancer screeninK system in Asian individuals.

Comparison and development of advanced machine learning tools to predict nonalcoholic fatty liver disease:An extended study

Background:Nonalcoholic fatty liver disease(NAFLD)is a public health challenge and significant cause of morbidity and mortality worldwide.Early identification is crucial for disease intervention.We recently proposed a nomogram-based NAFLD prediction model from a large population cohort.We aimed to explore machine learning tools in predicting NAFLD.Methods:A retrospective cross-sectional study was performed on 15315 Chinese subjects(10373 training and 4942 testing sets).Selected clinical and biochemical factors were evaluated by different types of machine learning algorithms to develop and validate seven predictive models.Nine evaluation indicators including area under the receiver operating characteristic curve(AUROC),area under the precision-recall curve(AUPRC),accuracy,positive predictive value,sensitivity,F1 score,Matthews correlation coefficient(MCC),specificity and negative prognostic value were applied to compare the performance among the models.The selected clinical and biochemical factors were ranked according to the importance in prediction ability.Results:Totally 4018/10373(38.74%)and 1860/4942(37.64%)subjects had ultrasound-proven NAFLD in the training and testing sets,respectively.Seven machine learning based models were developed and demonstrated good performance in predicting NAFLD.Among these models,the XGBoost model revealed the highest AUROC(0.873),AUPRC(0.810),accuracy(0.795),positive predictive value(0.806),F1 score(0.695),MCC(0.557),specificity(0.909),demonstrating the best prediction ability among the built models.Body mass index was the most valuable indicator to predict NAFLD according to the feature ranking scores.Conclusions:The XGBoost model has the best overall prediction ability for diagnosing NAFLD.The novel machine learning tools provide considerable beneficial potential in NAFLD screening.