[Why is the so-called most readily detectable cancer not detected, diagnosed and treated in its early stage?].
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Comparisons of cancer detection rate and costs of one cancer detected among different age-cohorts in immunochemical occult blood screening.
PURPOSE: This study was carried out to compare the detection rate for colorectal cancer and the average costs to detect one patient with colorectal cancer among three different age-cohorts in immunochemical occult blood screening by OC-Hemodia. METHODS: In a population-screening program, 17,432 subjects received an immunochemical fecal occult blood test. In a medical checkup for colorectal cancer 7,232 subjects received colonoscopy. They were divided into three groups according to their ages: younger (4,049 years); middle (50-59); and older (60+) groups. The detection rate for colorectal cancer and the average costs to detect one patient with colorectal cancer were evaluated among the three groups. RESULTS: In the screening program-based study, the cancer detection rate and the average costs for one colorectal cancer detected were calculated as 0.09% and $13,352, 0.28% and $4,555, 0.29% and $4,461 for the younger, middle, and older groups, respectively. In addition, in the medical checkup-based study, the detection rate and the average costs were calculated as 0.3% and $6,851, 1.5% and $1,517, 1.7% and $1,391 for the younger, middle, and older groups, respectively. In these two studies, the cancer detection rates were significantly different between the younger and middle groups (P < 0.05), and between the younger and older groups (P < 0.05). CONCLUSIONS: These findings indicate that the subjects aged under 50 have some disadvantage when carrying out the immunochemical fecal occult blood test--OC-Hemodia for colorectal cancer screening--from the viewpoint of screening efficiency as well as cost-effectiveness.
Adult↗
Pathology review in an early prostate cancer detection program: results from the American Cancer Society-National Prostate Cancer Detection Project.
Biopsy materials obtained in the American Cancer Society National Prostate Cancer Detection Project were reviewed at the Central Pathology Laboratory at the Armed Forces Institute of Pathology. Of 265 cases submitted, 177 were diagnosed as prostatic carcinoma, 7 as prostatic intraepithelial neoplasia (PIN), 13 as atypical glands or atypical hyperplasia, and the remaining 68 were benign hyperplasias. Irrespective of the means of detectin or the grading system used (Gleason or WHO-Mostofi), a large majority of the cancers were detected as low-grade tumors. Of 27 cases of PIN reported, 20 were associated with cancer, leaving 7 cases with the sole diagnosis of PIN. These data may indicate the increased use of prostate-specific antigen (PSA), digital rectal examination (DRE), and transrectal ultrasound (TRUS) in the United States is shifting the spectrum of prostate cancer pathology toward early low-grade tumors.
Biopsy↗
A comparison of cancer detection rates achieved by breast cancer screening programmes by number of readers, for one and two view mammography: results from the UK National Health Service breast screening programme.
OBJECTIVE: To determine the increased cancer detection rate, if any, of programmes in the UK National Health Service breast screening programme (NHSBSP) using more than single reading of mammograms. DESIGN: Information on the detection of cancers by individual screening programmes from annual (KC62) returns, supplemented by questionnaire information about the number of readers. SETTING: The 87 NHSBSP programmes from England and Wales for the screening year 1 April 1996 to 31 March 1997. The study includes all programmes for prevalent screens where two views are mandatory, but excludes the four programmes using two view mammography for incident screening. MAIN OUTCOME MEASURES: Cancer detection, invasive cancer detection, and small (< 15 mm) invasive cancer detection by mammographic reading protocol using single reading as the reference level. RESULTS: Programmes collectively using single reading detected the lowest rate of cancers at both prevalent (first) and incident (subsequent) screening. The highest rate of age standardised cancer detection was achieved by programmes using double reading with arbitration. At prevalent screens, where all programmes used two views, those programmes using double reading with arbitration detected 32% (95% confidence interval (CI) 3% to 69%) more small (< 15 mm) invasive cancers than programmes using single reading. At incident screens, where all programmes analysed used one view this increased to 73% (95% CI 40% to 113%). Recall rates showed no obvious difference between single reading and the double reading protocols, being around 7% for prevalent screens and 3.5% for incident screens. DISCUSSION: The results suggest that the increase in cancer detection resulting from increasing the number of readers depends on the number of views, and is higher for one view than two views. Single reading of one view results in a low detection rate of small invasive cancers for most individual programmes. It is, however, recognised that a small number of individual readers may achieve high detection rates with such a protocol. All groups of programmes using different reader/view protocols are on average close to or above target cancer detection rates, except those using single reading of one view (mediolateral oblique) at incident screens.
Breast Neoplasms↗
Prospective evaluation of systematic sextant transition zone biopsies in large prostates for cancer detection.
OBJECTIVES: A prospective evaluation was performed to define the role of systematic transition zone (TZ) biopsies in prostates larger than 50 cc. METHODS: From August 1994 to July 1997, 213 consecutive patients referred because of an abnormal digital rectal examination or prostate-specific antigen greater than 4.0 ng/mL had a calculated prostate size greater than 50 cc by transrectal ultrasound (TRUS) measurement. These patients underwent TRUS-guided sextant biopsies of the peripheral zone (PZ) and TZ. RESULTS: The median calculated prostate size was 70 cc with a TZ size of 39 cc. Fifty-five cases of carcinoma of the prostate were found, giving a 26% detection rate. The TZ biopsies detected cancer in 30 of the 55 patients (55% sensitivity) compared with the 47 patients detected by the PZ biopsies (85% sensitivity). Seven cancers (13%) were detected only by the additional TZ biopsies. TZ biopsies revealed bilateral tumors when the PZ biopsies had shown unilateral disease in 2 cases. In 6 cases the TZ biopsies showed higher Gleason grade tumors than was found in the PZ. In the 30 cases with positive TZ biopsy, concordance between the PZ and TZ biopsies occurred in 74% (133 of 180) of the sectors. The PZ biopsy detected cancer in 43 of 66 corresponding sectors that had positive TZ biopsies, giving a sensitivity of 65% and a negative predictive value of 80%. CONCLUSIONS: Routine PZ biopsies missed detecting 13% of the cancers found with the addition of sextant TZ biopsies in patients with large prostates (greater than 50 cc). In addition, 14% of the patients with cancer had upgrading or detection of bilateral tumor with the added biopsies. Routine systematic sextant TZ biopsies should be considered in patients with prostates greater than 50 cc in size.
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Circulating microRNA panels for multi-cancer detection and gastric cancer screening: leveraging a network biology approach.
BACKGROUND: Screening tests, particularly liquid biopsy with circulating miRNAs, hold significant potential for non-invasive cancer detection before symptoms manifest. METHODS: This study aimed to identify biomarkers with high sensitivity and specificity for multiple and specific cancer screening. 972 Serum miRNA profiles were compared across thirteen cancer types and healthy individuals using weighted miRNA co-expression network analysis. To prioritize miRNAs, module membership measure and miRNA trait significance were employed. Subsequently, for specific cancer screening, gastric cancer was focused on, using a similar strategy and a further step of preservation analysis. Machine learning techniques were then applied to evaluate two distinct miRNA panels: one for multi-cancer screening and another for gastric cancer classification. RESULTS: The first panel (hsa-miR-8073, hsa-miR-614, hsa-miR-548ah-5p, hsa-miR-1258) achieved 96.1% accuracy, 96% specificity, and 98.6% sensitivity in multi-cancer screening. The second panel (hsa-miR-1228-5p, hsa-miR-1343-3p, hsa-miR-6765-5p, hsa-miR-6787-5p) showed promise in detecting gastric cancer with 87% accuracy, 90% specificity, and 89% sensitivity. CONCLUSIONS: Both panels exhibit potential for patient classification in diagnostic and prognostic applications, highlighting the significance of liquid biopsy in advancing cancer screening methodologies.
Neoplasms↗
The American Cancer Society National Prostate Cancer Detection Project and National patterns of prostate cancer detection and treatment.
The ACS National Prostate Cancer Detection Project was established in 1987 to demonstrate the feasibility of early detection as a cancer control strategy for prostate cancer. Ten years later, the compliance results suggest that early detection programs can achieve long-term participation in a healthy population.
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The Liverpool Lung Project: a molecular epidemiological study of early lung cancer detection.
Lung cancer is the major cause of death from neoplastic disease in the world, and even with politically-motivated smoking cessation campaigns throughout Europe, the disease remains the major cause of death. The development of molecular epidemiological population-based research into early lung cancer detection, such as the Liverpool Lung Project (LLP), may provide a way forward. This is the first major molecular epidemiological study of detection of early lung cancer. The use of molecular epidemiological risk assessments prior to clinical diagnosis and markers of preclinical carcinogenesis in patients with a high risk of developing lung cancer will reduce the incidence of clinically-detectable lung cancer, given the appropriate intervention strategies. The aims are as follows: 1) to prepare a molecular genetic and epidemiological risk assessment model based on environmental exposures and genetic predisposition; 2) to develop an archive of specimens relating to at-risk individuals and those with lung cancer; 3) to redefine lung cancer based on molecular pathology using the fields of expression profiling, genetic instability and molecular cytogenetics; 4) to identify and assess novel markers of precarcinogenesis in high-risk populations; and 5) to facilitate the development of new treatment strategies (e.g. chemoprevention programmes and targeted drug therapies). The LLP has two components: 1) a case-controlled study of newly-diagnosed cases of lung cancer that will provide a baseline, risk assessment; and 2) a prospective cohort study to be carried out over a 10-yr period that will identify markers of preclinical carcinogenesis. In-depth interviews are carried out using structured and semi-structured questionnaires. Sputum, blood and tumour specimens are collected and will be assessed for specific molecular markers (e.g. genetic instability, mutation and expression profiling, and methylation status). Conclusions from The Liverpool Lung Project will be based around molecular-epidemiological and genotyping risk assessment models, as well as redefining the disease, and ultimately contributing to the development of new early lung cancer detection and treatment strategies.
Age Factors↗
Age-related cancer detection rate and costs for one cancer detected in one screening by immunochemical fecal occult blood test.
PURPOSE: This study was performed to assess, from the aspects of screening efficiency and cost-effectiveness, the optimal lower limit of age in immunochemical occult blood screening for colorectal cancer. METHODS: Seven thousand four hundred asymptomatic individuals were the subjects of this study. They gave samples for an immunochemical fecal occult blood test (OC-Hemodia), and colonoscopy was performed during a medical checkup. They were divided into three groups according to their ages: younger (40-49), middle (50-59), and older (60+) groups. The detection rate for colorectal cancer and the average costs to detect one patient with colorectal cancer were evaluated among the three groups. RESULTS: The detection rate for colorectal cancer and the average costs to detect one cancer patient were calculated as 0.3 percent and $6024 for the younger group, 1.6 percent and $1425 for the middle group, and 1.7 percent and $1410 for the older group, respectively. The cancer detection rate was significantly different between the younger and middle groups (P < 0.05) and between the younger and older groups (P < 0.05). CONCLUSIONS: This analysis suggests that the subjects aged less than 50 have some disadvantage when carrying out the immunochemical fecal occult blood test, OC-Hemodia for colorectal cancer screening, from the aspects of screening efficiency and cost-effectiveness.
Adult↗
Negative correlation between poly-ADP-ribosylation of spleen cell histone proteins and initial duration of dimethylnitrosamine exposure to mice in vivo measured by Western blot immunoprobe assay: a possible biomarker for cancer detection.
Improved cancer detection involving suitable biomarkers with easy applicability is a challenge to our fight against cancer. Poly-ADP-ribosylation (PAR) of proteins is a likely candidate biomarker for this purpose because it meets the criterion well. This report is a step towards testing suitability of PAR as a biomarker for cancer detection. Swiss albino mice were exposed to hepatocarcinogen, dimethylnitrosamine (DMN), at a chronic dose, which is known to induce carcinogenesis in liver. PAR was monitored by a Western blot immunoprobe assay in spleen, a lymphoid organ, to find a correlation between PAR of spleen histone proteins and duration of DMN exposure. A negative, non-linear correlation was found for most histone proteins. The inhibition of PAR of histones was significant from 4 weeks onwards until the end of the observation. The inhibition was potentiated when 3-aminobenzamide was simultaneously administered. The results open up the possibility of PAR of cellular proteins being used as biomarker for cancer detection.
Animals↗
Pathological features of prostate cancer detected on initial and repeat prostate biopsy: results of the prospective European Prostate Cancer Detection study.
PURPOSE: We evaluated pathological features of prostate cancer detected on repeat prostate biopsy in men with a serum total prostate-specific antigen (PSA) level between 4 and 10 ng/ml who were diagnosed with benign prostatic tissue after an initial biopsy and compared them to those cancers detected on initial prostate biopsy. MATERIALS AND METHODS: In this prospective European prostate cancer detection study, 1,051 men with a total PSA level between 4 and 10 ng/ml underwent transrectal ultrasound (TRUS)-guided sextant biopsy and two additional transition zone biopsies. All subjects whose biopsy samples were negative for prostate cancer (CaP) underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers underwent radical prostatectomy. Pathological and clinical features of patients diagnosed with cancer on either initial or repeat biopsy and clinically organ confined disease who agreed to undergo radical prostatectomy were compared. RESULTS: Initial biopsy was positive (CaP) in 231 of 1,051 enrolled subjects and negative (benign histology) in 820 subjects. Of these 820 subjects, CaP was detected in 10% (83/820) upon repeat biopsy. Of cancers detected on initial and repeat biopsy, 148/231 (64%) and 56/83 (67.5%) had clinically localized disease, respectively, and were offered radical prostatectomy. 10/148 (6.7%) and 3/56 (5.3%), respectively, opted for radiation therapy and thus, 138/148 (93.3%) and 53/56 (94.7%), respectively, underwent radical retropubic prostatectomy. There were statistically significant differences with respect to multifocality (P = 0.009) and cancer location (P < 0.001) with cancers on repeat biopsy showing a lower rate of multifocality and a more apico-dorsal location. In contrast, there were no differences with respect to stage (P = 0.2), Gleason score (P = 0.36), percentage Gleason grade 4/5 (P = 0.1), serum PSA (P = 0.62), and patient age (P = 0.517). CONCLUSIONS: At least 10% of patients with negative prostatic biopsy results will be diagnosed with CaP on repeat biopsy. Despite differences in location and multifocality, pathological and biochemical features of cancers detected on initial and repeat biopsy are similar, suggesting similar biological behavior and thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy. Cancers missed on initial biopsy and subsequently detected on repeat biopsy are located in a more apico-dorsal location. Repeat biopsies should thus be directed to this rather spared area in order to improve cancer detection rates.
Age Factors↗
Cancer detection; a report from the Cancer Detection Center, University of Minnesota.
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Biomedical Research↗
The American Cancer Society National Prostate Cancer Detection Project. Findings on the detection of early prostate cancer in 2425 men.
The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) is a multidisciplinary, multicenter effort to assess the feasibility of early prostate cancer detection by digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA) assay. By June 1990, 2425 men not previously suspected of having prostate cancer had been examined in ten participating clinical centers according to the project protocol. Three hundred ninety-six men (16.3%) were recommended for biopsy on the basis of TRUS or DRE. An analysis of the results of 330 completed biopsies showed 52 cancers detected by DRE and/or TRUS. Forty-four (84.6%) of the men with cancer had positive TRUS examination results compared with 33 (63.5%) with positive DRE. Five additional cancers were discovered as a result of elevated PSA levels. The overall detection rate was 2.4% and this rate varied by age. The detection rate in men 55 to 60 years of age was 1.3% and this rose to 3.3% in men older than 65 years of age. The estimated sensitivity was significantly greater for TRUS compared with DRE (77.2% versus 57.9%; P less than 0.05). The estimated specificity of DRE was greater than that of TRUS (96.3% versus 89.4%; P less than 0.01). The positive predictive value (PPV) for the tests varied as a function of patient and disease characteristics. The overall PPV was 28.0% for DRE and 15.2% for TRUS. The occurrence of elevated PSA levels significantly increased the PPV of both TRUS and DRE. The majority of cancers detected were at early stages. These preliminary data suggest the feasibility of using these techniques to promote cancer control, but additional data and follow-up are needed to assess the significance of the results.
Age Factors↗
Early detection of prostate cancer: the nature of cancers detected with current diagnostic tests.
The goal of an early detection program is not to detect all prostate cancers, but only to detect those that are potentially morbid or lethal (clinically important cancers). The prevalence of such cancers in the population of 50-year-old men can be estimated to be about 6%, using both epidemiologic and pathologic data. Screening trials using PSA and/or TRUS instead of or in addition to DRE have approached this rate of detection. As Fig 1 illustrates, screening appears to detect almost all of the clinically important cancers in the study population. The fear that these tests will detect a high proportion of latent, or clinically unimportant, cancers appears to be unfounded. Our studies and those of others support the concept that 85% to 90% of cancers detectable with current tests are clinically important. The detection of nonpalpable cancers by PSA or TRUS reduces the proportion of cancers detected at an advanced stage without increasing significantly the detection of latent or clinically unimportant cancers. Despite this analysis, we still lack definitive data to show that screening and treating early stage cancers will decrease the mortality rate of this disease. Such a conclusion will require a long-term, randomized screening trial or a comparison of mortality rates among large populations of men differing primarily in the extent of screening for prostate cancer.
Biopsy↗
Primary colorectal cancers detected with PET.
Positron emission tomography (PET) using 18F-fluorodeoxyglucose can sensitively detect cancers of increased glucose metabolism. We describe three asymptomatic individuals who were found to have colorectal cancer and underwent potentially curative surgery. On the PET images, lesions were easily discernible. Our experience and the experience of others suggest that primary colorectal cancer can be detected with PET in a resectable stage. Our three cases are presented and the potential utility of PET is discussed.
Adult↗
Cost-effective prostate cancer detection. Reduction of low-yield biopsies. Investigators of the American Cancer Society National Prostate Cancer Detection Project.
BACKGROUND: In hopes of limiting low-yield prostate biopsies, results of digital rectal examination (DRE), transrectal ultrasound (TRUS), prostate specific antigen (PSA) and age-related PSA values, gland-volume-adjusted PSA levels, and longitudinal PSA changes were analyzed to identify their cost-effectiveness as prognostic indicators in screening, biopsy, and follow-up of patients with prostate cancer. METHODS: Twenty-nine hundred men with complete data sets from an initial cohort of 2999 men with an annual follow-up for up to 5 years were examined. Intrapatient PSA and gland-volume variability, optimal PSA operating points (o.p.), and test performance scores were determined for each parameter. Decision analysis was then applied retrospectively to each parameter to determine the cancer detection yield, biopsy requirements, and costs for commonly used detection strategies. RESULTS: For the initial screening decision, the optimal PSA o.p. was 3.0 ng/ml but increased to 5.0 ng/ml in combination with DRE, whereas age-related PSA performed no better than did PSA. The mean intrapatient variability in TRUS gland volume (+5.5 cc) relative to mean volume (34 cc) was 16%, which was less than the 28% (0.64/2.3 ng/ml) relative variability for PSA. For biopsy decisions, using PSA density (PSAD) with a level of 0.12 ng/ml/cc there was no significant difference in accuracy compared with the systematic biopsy of all patients with elevated PSA or age-related PSA levels. Rather than perform systematic biopsy on all patients with PSA levels greater than 4 ng/ml, decision analysis showed that a 16-55% reduction in biopsies could be achieved with a respective cancer loss of 4-25% by limiting biopsy to patients with an increased PSAD level and/or abnormal results of DRE. Using age-related PSA criteria in combination with DRE reduced biopsies by 12% but resulted in minimal cost reductions. The greatest biopsy reduction relative to cancer yield and lowest cost per cancer detected occurred with PSAD-driven biopsy strategies. During follow-up, longitudinal changes in absolute PSA and PSAD levels were significantly better (P < 0.05) than the percentage change in PSA levels per year. CONCLUSIONS: Cost-effective prostate cancer detection with PSA as a parameter is better achieved if screening and biopsy decisions are not linked intimately. A tailored-biopsy approach for patients with disproportionately elevated PSA levels of suspicious DRE results in the greatest biopsy reduction by selecting lower risk groups for more conservative follow-up.
Age Factors↗
A comparison of invasive breast cancer detected in a screened population with invasive breast cancers detected at rapid access diagnostic facilities.
The objective of this study was to assess the impact of rapid access breast diagnostic facilities on the benefit of mammographic breast screening. Invasive cancers were compared for maximum diameter in two groups: group A--70 patients, with screen detected breast cancer aged 50-65, mean age 55.8; group B--46 patients, with symptomatic breast cancer aged 50-65, mean age 56.7. Group A patients had all been invited for screening and included interval cancers and cancers in lapsed attenders. Group B patients were detected at rapid access diagnostic facilities. In group A (screened) the invasive cancers had a mean diameter of 17.8 mm, with a median of 15 mm. Group B (unscreened) consisted of invasive cancers with a mean diameter of 25.2 mm, and a median of 25 mm. Thirty-two (46%) of the screened cancers were found to be less than 15 mm compared to 5 (11%) of the unscreened cancers, using the Wilcoxon Rank Sum Test, P<0.001. Although rapid access modern diagnostic facilities for breast cancers offer the ability to detect early cancers (11% in this survey), screen detected invasive cancers remain significantly smaller even when interval cancers and cancers in lapsed attenders are included.
Journal Article↗
Radiologic aspects of breast cancers detected through a breast cancer screening program.
Early detection of breast cancer and reduced mortality in women with this disease is today attributed to the widespread use of mammography. High-quality performance is essential in every step of breast cancer screening programs in order to avoid unnecessary anxiety and surgery in the women concerned. This report presents the radiologic aspects of screening cancers. A total of 8370 asymptomatic women aged between 50-69 years were screened with 2-view mammography, of which only 70 (0.84%) were selected for surgery after a thorough work-up. Cancers were verified histologically in 61 women and 9 showed non-malignant histology, giving a cancer detection rate of 7.3 cancers per thousand screened asymptomatic woman. The benign/malignant ratio in the operated cases is thus approximately 1:7. The cancers detected showed all existing types of mammographic features where 77% (47 cases) showed rather typical findings, such as spiculated densities both with and without microcalcifications and with microcalcifications only. The remaining 23% (14 cases) showed parenchymal distortions, asymmetric and well-defined densities, both with and without calcifications. Our results indicate that surgery can be minimized without impairing the breast cancer detection rate. Radiologists in screening programs should be aware that a large proportion of non-palpable breast cancers present in rather unconventional forms. This point is important in order to maintain a high cancer detection rate and thereby justify the widespread use of mammography as a screening tool for breast cancer in asymptomatic women.
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