Screen-detected Cases Research Articles

Screening and efficacy of radical prostatectomy

Screening and efficacy of radical prostatectomy

Limitations of basing screening policies on screening trials: The US Preventive Services Task Force and Prostate Cancer Screening.

The US Preventive Services Task Force recently recommended against prostate-specific antigen screening for prostate cancer based primarily on evidence from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. : To examine limitations of basing screening policy on evidence from screening trials. We reviewed published modeling studies that examined population and trial data. The studies (1) project the roles of screening and changes in primary treatment in the US mortality decline; (2) extrapolate the ERSPC mortality reduction to the long-term US setting; (3) estimate overdiagnosis based on US incidence trends; and (4) quantify the impact of control arm screening on PLCO mortality results. Screening plausibly explains 45% and changes in primary treatment can explain 33% of the US prostate cancer mortality decline. Extrapolating the ERSPC results to the long-term US setting implies an absolute mortality reduction at least 5 times greater than that observed in the trial. Approximately 28% of screen-detected cases are overdiagnosed in the United States versus 58% of screen-detected cases suggested by the ERSPC results. Control arm screening can explain the null result in the PLCO trial. Modeling studies indicate that population trends and trial results extended to the long-term population setting are consistent with greater benefit of prostate-specific antigen screening-and more favorable harm-benefit tradeoffs-than has been suggested by empirical trial evidence.

Mammographic density and risk of breast cancer according to tumor characteristics and mode of detection: a Spanish population-based case-control study.

IntroductionIt is not clear whether high mammographic density (MD) is equally associated with all subtypes of breast cancer (BC). We investigated the association between MD and subsequent BC, considering invasiveness, means of detection, pathologic subtype, and the time elapsed since mammographic exploration and BC diagnosis.MethodsBC cases occurring in the population of women who attended screening from 1997 through 2004 in Navarre, a Spanish region with a fully consolidated screening program, were identified via record linkage with the Navarre Cancer Registry (n = 1,172). Information was extracted from the records of their first attendance at screening in that period. For each case, we randomly selected four controls, matched by screening round, year of birth, and place of residence. Cases were classified according to invasiveness (ductal carcinoma in situ (DCIS) versus invasive tumors), pathologic subtype (considering hormonal receptors and HER2), and type of diagnosis (screen-detected versus interval cases). MD was evaluated by a single, experienced radiologist by using a semiquantitative scale. Data on BC risk factors were obtained by the screening program in the corresponding round. The association between MD and tumor subtype was assessed by using conditional logistic regression.ResultsMD was clearly associated with subsequent BC. The odds ratio (OR) for the highest MD category (MD >75%) compared with the reference category (MD <10%) was similar for DCIS (OR = 3.47; 95% CI = 1.46 to 8.27) and invasive tumors (OR = 2.95; 95% CI = 2.01 to 4.35). The excess risk was particularly high for interval cases (OR = 7.72; 95% CI = 4.02 to 14.81) in comparison with screened detected tumors (OR = 2.17; 95% CI = 1.40 to 3.36). Sensitivity analyses excluding interval cases diagnosed in the first year after MD assessment or immediately after an early recall to screening yielded similar results. No differences were seen regarding pathologic subtypes. The excess risk associated with MD persisted for at least 7 to 8 years after mammographic exploration.ConclusionsOur results confirm that MD is an important risk factor for all types of breast cancer. High breast density strongly increases the risk of developing an interval tumor, and this excess risk is not completely explained by a possible masking effect.

Potential effect of the risk of ovarian cancer algorithm (ROCA) on the mortality outcome of the Prostate, Lung, Colorectal and Ovarian (PLCO) trial

Recently, the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial reported no mortality benefit for annual screening with CA-125 and transvaginal ultrasound (TVU). Currently ongoing is the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), which utilizes the risk of ovarian cancer algorithm (ROCA), a statistical tool that considers current and past CA125 values to determine ovarian cancer risk. In contrast, PLCO used a single cutoff for CA125, based on current levels alone. We investigated whether having had used ROCA in PLCO could have, under optimal assumptions, resulted in a significant mortality benefit by applying ROCA to PLCO CA125 screening values. A best-case scenario assumed that all cancers showing a positive screen result earlier with ROCA than under the PLCO protocol would have avoided mortality; under a stage-shift scenario, such women were assigned survival equivalent to Stage I/II screen-detected cases. Updated PLCO data show 132 intervention arm ovarian cancer deaths versus 119 in usual care (relative risk, RR = 1.11). Forty-three ovarian cancer cases, 25 fatal, would have been detected earlier with ROCA, with a median (minimum) advance time for fatal cases of 344 (147) days. Best-case and stage-shift scenarios gave 25 and 19 deaths prevented with ROCA, for RRs of 0.90 (95% CI: 0.69-1.17) and 0.95 (95% CI: 0.74-1.23), respectively. Having utilized ROCA in PLCO would not have led to a significant mortality benefit of screening. However, ROCA could still show a significant effect in other screening trials, including UKCTOCS.

Abstract B06: Screening patterns within organized programs of Italian women with invasive cervical cancer

Abstract Background: The efficacy of organized cervical screening programs (OCSPs) in reducing, through the Pap-smear test, the burden of invasive cervical cancer (ICC) is well established. Opportunistic screening is widespread in Italy, while OCSP implementation is demanded to regional governments. In some regions, OCSPs have been implemented since the ‘90s whereas in others OCSPs do not cover the entire population yet. Objective: To describe screening patterns of women diagnosed with ICC, and to identify difficulties and limitations of OCSPs at a population level in Italy. Methods: OCSPs invite women aged 25-64 years to perform a free of charge Pap smear every 3 years. This study focused on 3268 women aged 25-65 years, diagnosed with ICC between 1995 and 2008, who lived in areas covered by population-based cancer registries (CRs) with active OCSPs. CRs and OCSPs databases were linked to classify each woman according to OCSP invitation, compliance with invitation, and Pap-smear results. Odds ratios (OR- adjusted for age at diagnosis) and 95% confidence intervals (CI) were computed using logistic regression models to assess the association between women characteristics, screening patterns, and ICC features. Among 2911 women (out of 3268) with updated vital status, hazard ratios (HR- adjusted for age and tumor stage) and 95% CI were computed using the Cox model to assess the impact of screening patterns on death risk. Results: Out of 3268 women with ICC, 657 (20.1%) were never invited for screening. Non invitation by OCSPs was inversely related with time elapsed between program activation and ICC diagnosis (OR=4.6, 95% CI: 3.7-5.9, for ≥3 years vs ≥6 years). Of the 2611 women with ICC invited by OCSPs, 1181 (45.2%) were noncompliant. Noncompliance was highest in southern Italy (80.6% vs 45.2% in the North -OR=4.9), and it significantly increased with aging. 66.8% of women with advanced ICC stage at diagnosis (FIGO III-IV) were noncompliant, as compared to 25.6% of those with micro-invasive stage (IA-IA1, OR=5.7). Among the 1430 compliant women, ICC was screen-detected by OCSPs in 1075 cases (75.2%) -in 794 cases at first Pap-smear and in 281 cases at a subsequent test. Conversely, in 355 cases (24.8%) ICC was non screen-detected -all Pap-smears made within OCSPs were negative. As compared to compliant women with screen-detected ICC, the risk of death was significantly higher in never compliant women (HR=2.0; 95%CI: 1.6-2.5), in never invited ones (HR=1.8; 95% CI 1.4-2.3), and in women with non screen-detected ICC (HR=1.7, 95%CI: 1.2-2.2). Conclusions: In Italy, about 56% of ICC cases diagnosed between 1995 and 2008 occurred in women from target populations for OCSPs who were never invited for screening, or who were noncompliant. Factors associated with lack of invitation and with non-adherence to OCSPs deserve attention, in view of the associated high risks of death. Screening history outside OCSPs should also be considered to fully evaluate non screen-detected ICC cases. Citation Format: Antonella Zucchetto, Guglielmo Ronco, Paolo Giorgi Rossi, Stefano Ferretti, Marco Zappa, Franzo Antonella, Falcini Fabio, Zanetti Roberto, Biavati Patrizia, Stracci Fabrizio, Zambon Paola, Federico Massimo, Diego Serraino, WORKING GROUP IMPATTO CERVICE. Screening patterns within organized programs of Italian women with invasive cervical cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B06.

Long‐term radical prostatectomy outcomes among participants from the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam

Study Type--Therapy (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Radical prostatectomy was previously shown to improve long-term outcomes among men with clinically-detected prostate cancer. Our data suggests that radical prostatectomy is also associated with improved outcomes in men with screen-detected prostate cancer. • To examine the long-term outcomes of radical prostatectomy (RP) among men diagnosed with prostate cancer from the screening and control arms of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). • Among 42,376 men randomised during the period of the first round of the trial (1993-1999), 1151 and 210 in the screening and control arms were diagnosed with prostate cancer, respectively. • Of these men, 420 (36.5%) screen-detected and 54 (25.7%) controls underwent RP with long-term follow-up data (median follow-up 9.9 years). • Progression-free (PFS), metastasis-free (MFS) and cancer-specific survival (CSS) rates were examined, and multivariable Cox proportional hazards models were used to determine whether screen-detected (vs control) was associated with RP outcomes after adjusting for standard predictors. • RP cases from the screening and control arms had statistically similar clinical stage and biopsy Gleason score, although screen-detected cases had significantly lower prostate-specific antigen (PSA) levels at diagnosis. • Men from the screening arm had a significantly higher PFS (P = 0.003), MFS (P < 0.001) and CSS (P = 0.048). • In multivariable models adjusting for age, PSA level, clinical stage, and biopsy Gleason score, the screening group had a significantly lower risk of biochemical recurrence (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23-0.83, P = 0.011) and metastasis (HR 0.18, 95% CI 0.06-0.59, P = 0.005). • Additionally adjusting for tumour volume and other RP pathology features, there was no longer a significant difference in biochemical recurrence between the screening and control arms. • Limitations of the present study include lead-time bias and non-randomised treatment selection. • After RP, screen-detected cases had significantly improved PFS, MFS and CSS compared with controls within the available follow-up time. • The screening arm remained significantly associated with lower rates of biochemical recurrence and metastasis after adjusting for other preoperative variables. • However, considering also RP pathology, the improved outcomes in the screening group appeared to be mediated by a significantly lower tumour volume.

A Stochastic Model for Calibrating the Survival Benefit of Screen-Detected Cancers

Comparison of the survival of clinically detected and screen-detected cancer cases from either population-based service screening programs or opportunistic screening is often distorted by both lead-time and length biases. Both are correlated with each other and are also affected by measurement errors and tumor attributes such as regional lymph node spread. We propose a general stochastic approach to calibrate the survival benefit of screen-detected cancers related to both biases, measurement errors, and tumor attributes. We apply our proposed method to breast cancer screening data from one arm of the Swedish Two-County trial in the trial period together with the subsequent service screening for the same cohort. When there is no calibration, the results—assuming a constant (exponentially distributed) post-lead-time hazard rate (i.e., a homogeneous stochastic process)—show a 57% reduction in breast cancer death over 25 years. After correction, the reduction was 30%, with approximately 12% of the overestimation being due to lead-time bias and 15% due to length bias. The additional impacts of measurement errors (sensitivity and specificity) depend on the type of the proposed model and follow-up time. The corresponding analysis when the Weibull distribution was applied—relaxing the assumption of a constant hazard rate—yielded similar findings and lacked statistical significance compared with the exponential model. The proposed calibration approach allows the benefit of a service cancer screening program to be fairly evaluated. This article has supplementary materials online.

The Potential for Risk Stratification in the Management of Ovarian Cancer Risk

Invasive epithelial ovarian cancer (EOC) is the most fatal malignancy of the female reproductive tract, causing more deaths than all other gynecologic cancers combined. Most cases are diagnosed at an advanced stage, and 5-year survival with EOC is less than 50%. Screening for EOC in the general population has not been found to be effective, with the recently reported results from the Prostate, Lung, Colorectal and Ovarian trial showing that there was no shift in the stage at diagnosis among the screen-detected cases and no reduction in mortality. Targeting screening at those at highest risk may prove to be more effective. An alternative approach to risk management is prophylactic surgery, which may be a useful option for women in the highest risk groups. In this article, I will summarize the current state of knowledge about ovarian cancer genetics and discuss how this knowledge may be used to target primary or secondary prevention in ovarian cancer.

Abstract IA6: Cell cycle progression genes differentiate indolent from aggressive prostate cancer

Abstract Background: In cancers with variable natural history, prognostic biomarkers are needed for selecting patients for therapeutic intervention. This is particularly true for prostate cancer, where many screen-detected cases are indolent and predicting adverse outcomes is difficult. Therefore, we developed an expression signature composed of genes involved in cell cycle progression (CCP) and tested its utility in prostate cancer. Methods: We developed a 46-gene prognostic RNA signature that is based on measuring the expression of CCP genes. The expression score (CCP score) is derived as the normalized mean expression all CCP genes in the signature. Results: The prognostic utility of the CCP score has been tested in both multiple clinical settings and patient populations. First, it was tested in a post-prostatectomy cohort from the U.S. where the CCP score predicted biochemical recurrence in univariate (χ2 = 34.0, 1df, p = 5·6 × 10-9) and multivariate analysis (χ2 = 21.65, 1df, p = 3.3 × 10-6). CCP score and PSA were the dominant variables in the best predictive model and were much more significant than any other clinical measure. Second, it was tested in a conservatively managed TURP cohort from the UK where the CCP score was the dominant variable for predicting death from prostate cancer in both univariate (χ2 = 92.7, 1df, p = 6.1 × 10-22) and multivariate analyses (χ2 = 42.2, p = 8.2 × 10-11). Third, it was tested in a conservatively managed needle biopsy cohort from the UK where the CCP score was a better univariate predictor of prostate cancer death than any other variable (χ2 = 37·6, 1df, p = 8.6 × 10-10). The best multivariate model from this study included Gleason and PSA, but CCP dominated (HR for one unit increase = 1.65, 95% CI (1.31, 2.09) χ2 = 17.7, P = 3 × 10-5) with Gleason score (χ2 = 12.1, P = 5 × 10-4) and baseline PSA (χ2 = 5.7, P = 0.017) providing significant, but smaller additional contributions. Conclusions: A CCP expression signature is prognostic in prostate cancer patients at diagnosis and after prostatectomy. It consistently provides information beyond clinical and pathological variables to help differentiate aggressive from indolent disease. Studies aimed at expanding the clinical utility of this signature are warranted and ongoing. Citation Format: Steven Stone, On behalf of the Transatlantic Prostate Group, Jack Cuzick, Dan Berney, Julia Reid, Gabrielle Fisher, Jerry Lanchbury, Alexander Gutin, Greg Swanson. Cell cycle progression genes differentiate indolent from aggressive prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA6.

A stochastic model for survival of early prostate cancer with adjustments for leadtime, length bias, and over‐detection

To compare the survival between screen-detected and clinically detected cancers, we applied a series of non-homogeneous stochastic processes to deal with leadtime, length bias, and over-detection by using full information on detection modes obtained from the Finnish randomized controlled trial for prostate cancer screening. The results show after 9-year follow-up the hazard ratio of prostate cancer death for screen-detected cases against clinically detected cases increased from 0.24 (95% CI: 0.16-0.35) without correction for these biases, to 0.76 after correction for leadtime and length biases, and finally to 1.03 (95% CI: 0.79-1.33) for a further adjustment for over-detection. Adjustment for leadtime and length bias but no over-detection led to a 24% reduction in prostate cancer death as a result of prostate-specific antigen test. The further calibration of over-detection indicates no gain in survival of screen-detected prostate cancers (excluding over-detected case as stayer considered in the mover-stayer model) as compared with the control group in the absence of screening that is considered as the mover. However, whether the model assumption on over-detection is robust should be validated with other data sets and longer follow-up.

Impact of Screening and Risk Factors for Local Recurrence and Survival After Conservative Surgery and Radiotherapy for Early Breast Cancer: Results From a Large Series With Long-Term Follow-Up

To investigate conventional prognostic factors for ipsilateral breast tumor recurrence (IBTR), distant metastasis (DM), and survival after breast-conserving therapy (BCT) in screen-detected and symptomatic cases on surveillance up to 25 years. A total of 1812 consecutive patients in three cohorts (1981-1989, 1990-1992, and 1993-1998) with T12N01M0 invasive breast cancer were treated with BCT (median follow-up, 14 years). Tumor type and grade were reviewed by a single pathologist. Hormone receptor status was measured by immunohistochemistry on tissue microarrays. A Cox proportional hazards model was used to assess independent prognostic variables for relapse and survival. A total of 205 IBTR occurred, with 5-, 10-, 15-, and 20-year actuarial relapse rates of 4.5% (95% confidence interval [CI] 3.35-5.5%), 8.4% (95% CI 7.1-9.8%), 14.1% (95% CI 12.0-16%), and 17.4% (95% CI 14.5-20.2%). Number of nodes, young age, pathologic tumor size, and multifocality were significant factors for IBTR. Three hundred seventy-eight patients developed DM. The actuarial metastatic rate was 12% at 5 years and 17.9% at 10 years. Young age, number of positive nodes, pathologic tumor size, and tumor grade were significant factors for DM relapse. When conventional prognostic indices were taken into account screen-detected cancers showed no improvement in overall relapse or survival rate compared with symptomatic cases but did show a reduced risk of DM after IBTR. After 10 years IBTR relapse continued at a constant rate of 0.87% per annum. The Edinburgh BCT series has shown that screen-detected invasive breast cancers do not have significantly different clinical outcomes compared with symptomatic cases when pathologic risk factors are taken into account. This suggests that these patients be managed in a similar way.

P1-11-11: Wait Times for Breast Cancer Care in Manitoba 2009–2010. Time To Face the Challenge.

Abstract Background: Wait times for patients with breast cancer to receive oncological treatment vary significantly. In Manitoba, the radiation treatment wait times improved in the year 2005 compared to 2001. However, other parts of the patient's journey have lengthened and negated the reduction seen in radiation treatment wait times. Aims: To examine the overall time from disease suspicion to treatment of breast cancer patients from June 2009 to June 2010 and to compare to the previously published wait times. Methods: This population-based retrospective study looked at representative samples of women newly diagnosed with breast cancer. Patients were followed from the time of first presentation, either to their family physician or after a suspicious screening mammogram, to the time adjuvant treatment was started. Each patient's journey was subdivided into different chronological stages. The data was compared to the wait times reported in 2005. Results: 363 patients’ data was collected and analyzed. The median elapsed time in days for each phase of the journey was calculated. Total wait times from suspicion to diagnosis were also calculated. The wait times of most stages of the patients’ journey have worsened when compared to 2005. However, there was some improvement in the diagnostic part of the journey. Delays to surgery and pathology have contributed to lengthening of the total journey. There was also a systematic and repetitive administration delay at each transition. Screen-detected cases had a shorter journey than those who presented through a family physician. Conclusions: In spite of improvements achieved in the wait times at some stages of the journey, the total length of the patient journey has not been shortened. This represents not only individual team failures but also a built in complexity in the health system. In order to achieve a meaningful cut in wait times for breast cancer patients, the entire trajectory of care needs to be addressed. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-11.

Evaluating the long-term effect of FOBT in colorectal cancer screening

Background Cancer screening has been effective in detecting tumors early before symptoms appear. However, the effectiveness of the regular fecal occult blood test (FOBT) in colorectal cancer in the long term has not been quantified. Methods We applied the statistical method developed by Wu and Rosner [1] using data from the Minnesota Colon Cancer Control Study (MCCCS). All initially asymptomatic participants were classified into four mutually exclusive groups: true-early-detection, no-early-detection, over-diagnosis, and symptom-free life; human lifetime was treated as a random variable and is subject to competing risks. All participants in the screening program will eventually fall into one of the four outcomes above. Predictive inferences on the percentages of the four outcomes for both genders were made using the Minnesota study data. Results Depending on gender, screening frequency and age at the initial screening, for all participants the probability of “symptom-free-life” varies between 95.3% and 96.6%; the probability of “true-early-detection” is 1.9–3.8%; the probability of no-early-detection is 0.3–2.0%; the probability of over-diagnosis is 0.16–0.3%. Among those with colorectal cancer detected by regular FOBT, the probability of over-diagnosis is lower than expected and is between 6% and 9%, with 95% CI (2.5%, 21.3%) for females and (1.9%, 44.7%) for males. The probability of true-early-detection increases as screening interval decreases. The probability of no-early-detection decreases as screening interval decreases. Conclusion The probability of over-diagnosis among the screen-detected cases is not as high as previously thought. We hope this outcome can provide valuable information on the effectiveness of the FOBT in colorectal cancer detection in the long term.

Towards an Optimal Interval for Prostate Cancer Screening

BackgroundThe rate of decrease in advanced cancers is an estimate for determining prostate cancer (PCa) screening program effectiveness. ObjectiveAssess the effectiveness of PCa screening programs using a 2- or 4-yr screening interval. Design, setting, and participantsMen aged 55–64 yr were participants at two centers of the European Randomized Study of Screening for Prostate Cancer: Gothenburg, Sweden (2-yr screening interval, n=4202), and Rotterdam, the Netherlands (4-yr screening interval, n=13 301). We followed participants until the date of PCa, the date of death, or the last follow-up at December 31, 2008, or up to a maximum of 12 yr after initial screening. Potentially life-threatening (advanced) cancer was defined as cancer with at least one of following characteristics: clinical stage ≥T3a, M1, or N1; serum prostate-specific antigen (PSA) >20.0 ng/ml; or Gleason score ≥8 at biopsy. InterventionWe compared the proportional total (advanced) cancer incidence (screen-detected and interval cases), defined as the ratio of the observed number of (advanced) cancers to the expected numbers of (advanced) cancers based on the control arm of the study. MeasurementsThe proportional cancer incidence from the second screening round until the end of observation was compared using a 2- or 4-yr screening interval. Results and limitationsFrom screening round 2 until the end of observation, the proportional cancer incidence was 3.64 in Gothenburg and 3.08 in Rotterdam (relative risk [RR]: 1.18; 95% confidence interval [CI], 1.04–1.33; p=0.009). The proportional advanced cancer incidence was 0.40 in Gothenburg and 0.69 in Rotterdam (RR: 0.57; 95% CI, 0.33–0.99; p=0.048); the RR for detection of low-risk PCa was 1.46 (95% CI, 1.25–1.71; p<0.001). This study was limited by the assumption that PSA testing in the control arm was similar in both centers. ConclusionsA 2-yr screening interval significantly reduced the incidence of advanced PCa; however, the 2-yr interval increased the overall risk of being diagnosed with (low-risk) PCa compared with a 4-yr interval in men aged 55–64 yr. Individualized screening algorithms must be improved to provide the strategy for this issue.

Performance of gastric cancer screening by endoscopy testing through the National Cancer Screening Program of Korea

Recent reports have proposed endoscopy as an alternative strategy to radiography for gastric cancer (GC) screening. The current study presents the first reported population-based data from a large GC screening program that provided endoscopic examinations. A retrospective population-based study was conducted using the National Cancer Screening Program (NCSP) database. We evaluated GC detection rates, sensitivity, specificity, and the positive predictive value of an endoscopic screening program for the average-risk Korean population, aged 40 years and older, who underwent the NCSP from 2002 to 2005. The detection rates of GC by endoscopy in the first and subsequent rounds were 2.71 and 2.14 per 1000 examinations, respectively. Localized cancer accounted for 45.7% of screen-detected GC cases. The sensitivity of endoscopy was 69% (95% confidence interval [CI]: 66.3-71.8). The endoscopic screening was less sensitive for the detection of localized GC (65.7%, 95% CI = 61.8-69.5) than for regional or distant GC (73.6%, 95% CI = 67.4-79.8). In the multiple logistic models for localized GC and all combined GC, the odds ratio (OR) of sensitivity for the undifferentiated type was statistically significantly higher than that for the differentiated type, whereas the OR of sensitivity for the mixed type was lower than that for the differentiated type. The sensitivity of the endoscopic test in a population-based screening was slightly higher for the detection of regional or distant GC than for localized GC. Further evaluation of the impact of endoscopic screening should take into account the balance of cost and mortality reduction.

Prostate Cancer Incidence and Disease-Specific Survival of Men with Initial Prostate-Specific Antigen Less Than 3.0 ng/ml Who Are Participating in ERSPC Rotterdam

BackgroundThe European Randomised Study of Screening for Prostate Cancer (ERSPC) applies a prostate-specific antigen (PSA) cut-off value ≥3.0ng/ml as an indication for lateralised sextant biopsy. ObjectiveTo analyse the incidence and disease-specific mortality for prostate cancer (PCa) in men with an initial PSA <3.0ng/ml. Design, setting and participantsFrom November 1993 to December 1999, a total of 42 376 men identified from population registries in the Rotterdam region (55–74 yr of age) were randomised to an intervention or control arm. A total of 19 950 men were screened during the first screening round. InterventionA PSA <3.0ng/ml was below the biopsy threshold. PCa cases were identified at rescreens every 4 yr or as interval cancers. MeasurementsDistribution of incidence, aggressiveness, and disease-specific mortality of PCa per PSA range was measured. Causes of death were evaluated by an independent committee, and follow-up was complete until 31 December 2008. Results and limitationsFrom 1993 to 2008, 915 PCa cases were diagnosed in 15 758 men (5.8%) with an initial PSA <3.0ng/ml and a median age of 62.3 yr. Median overall follow-up was 11 yr. PCa incidence increased significantly with higher initial PSA levels. Aggressive PCa (clinical stage ≥T2c, Gleason score ≥8, PSA >20ng/ml, positive lymph nodes, or metastases at diagnosis) was detected in 66 of 733 screen-detected PCa cases (9.0%) and 72 of 182 interval-detected PCa cases (39.6%). Twenty-three PCa deaths occurred in the total population (0.15%), with an increasing risk of PCa mortality in men with higher initial PSA values. ConclusionsThe risk of PCa, aggressive PCa and PCa mortality in a screening population with initial PSA <3.0ng/ml increases significantly with higher initial PSA levels. These results contribute to the risk stratification and individual management of men in PSA-based screening programmes.

Comparison of Clinical-Pathologic Characteristics and Outcomes of True Interval and Screen-Detected Invasive Breast Cancer Among Participants of a Canadian Breast Screening Program: A Nested Case-Control Study

Background Previous analyses of interval breast cancers have been limited because of a lack of control for screening interval length and patient age, failure to restrict the interval group to ‘true' intervals, and incomplete descriptions of pathology, adjuvant therapies and clinical outcomes. Patients and Methods A nested case-control study within the population-based Nova Scotia Breast Screening Program was performed. All true interval cases between 1991 and 2004 were identified, matched 1:2 to screen-detected cases (age, screening interval, time period), and compared in terms of pathologic characteristics and adjuvant therapies via logistic regression. Disease-free and overall survival was estimated, controlling for pathology and adjuvant chemotherapy receipt. Results A total of 241 true interval invasive cases were matched to 481 screen-detected cases. Interval cases were more likely to be > 1 cm (odds ratio [OR] = 1.76; 95% CI, 1.10-2.83), grade 3 (OR = 2.71; 95% CI, 1.49-4.92), and have lymphovascular invasion (OR = 3.06; 95% CI, 1.85-5.07). Interval cases received more adjuvant chemotherapy (OR = 4.37; 95% CI, 3.03-6.30) and radiation (OR = 1.43; 95% CI, 1.02-2.00). The 5-year Kaplan-Meier estimates of disease-free and overall survival rates for true intervals and screens were 0.830 (95% CI, 0.770-0.875) versus 0.926 (95% CI, 0.898-0.947) and 0.860 (95% CI, 0.804-0.901) versus 0.937 (95% CI, 0.910-0.956), respectively. Conclusion True interval breast cancers have more adverse prognostic factors compared with screen-detected cases and, despite receiving more adjuvant chemotherapy, are associated with significantly poorer survival outcomes.

Systematic review of primary hyperparathyroidism in India: the past, present, and the future trends.

Primary hyperparathyroidism (PHPT) has become an asymptomatic disease in the Western world with the introduction of routine calcium screening. However, the same phenomenon is not observed in India. We have now systematically reviewed the status of PHPT in India. While there is a paucity of literature on PHPT from India when compared to Western countries, some information can be gleaned upon. Most patients present with symptomatic disease whereas very few are screen-detected cases (bone disease 77%, renal disease 36%, and 5.6% asymptomatic). Mean calcium, parathyroid hormone (PTH), and alkaline phosphate levels are high while Vitamin D levels are low. The average parathyroid gland weight is large and the majority being parathyroid adenomas (89.1%). Hungry bone syndrome (HBS) is common in the postoperative period. The disease-related mortality rate is 7.4%, recurrence 4.16%, and persistent disease 2.17%. We suggest that dedicated efforts are needed to pick up asymptomatic disease in India by methods like incorporating calcium estimation in the routine health check-up programs.

Perspective on prostate cancer screening

Cancer screening has become an obligatory appendix to all periodic and continuity care of adults. It is ritualistic and seldom questioned. It is discrete and modular and so easily audited for 'quality'. Its impact on actual health ranges from slightly helpful to slightly harmful, and even these conclusions are usually more than slightly speculative. While, in some cases, the existing data includes the probability of an occasional life saved, all screening programmes increase many-fold the lifetime chance of confronting a false alarm and thus becoming, for a time, a cancer patient.

Lead-time in the European Randomised Study of Screening for Prostate Cancer

Background Lead-time is defined as the time by which screening advances the diagnosis compared with absence of screening. A sufficiently long lead-time needs to be achieved so that cancer can be detected while still curable. A very short lead-time may indicate poor sensitivity of the screening test, while a very long lead-time suggests overdiagnosis. Material and methods In the first screening round, a total of 56,294 men aged 55–74 years were screened with serum prostate specific antigen (PSA) in five countries of the European Randomised Study of Screening for Prostate Cancer (ERSPC) with an overall detection rate (prevalence) of 2.8% (1972 prostate cancers). Prostate cancer incidence among 92,142 men randomly allocated to the control arm of the trial was also assessed. Lead-time was estimated as the time required to accumulate a similar cumulative risk of prostate cancer in the control arm to the detection rate in the intervention arm, i.e. from the ratio of detection rate (prevalence of screen-detected cases) and expected incidence (cumulative risk). Results Using a serum PSA cut-off of 4 ng/ml, the mean lead-time in the whole study population was estimated as 6.8 years (95% confidence interval (95% CI) 7.9–8.4). It was 8 years in The Netherlands, 6 in Sweden and Finland, 5 in Italy and 4 in Belgium. The mean lead-time was similar, 6–7 years, at ages 50–64 years, but close to 8 years among men aged 65–74 years. A lower PSA cut-off level of 3 ng/ml used in Sweden and The Netherlands prolonged the mean lead-time by approximately 1 year. Lead-time based on advanced prostate cancer only was slightly shorter, mean 5.3 years (95% CI 4.6–6.0). The lead-time for the second screening round was slightly shorter than that for the first (5.9, 95% CI 5.4–6.4), reflecting a similar relation between detection rate and control group incidence. Conclusion The lead-time for prostate cancer found in ERSPC substantially exceeded that found for breast, cervical and colorectal cancer screening. One round of prostate cancer screening can advance clinical diagnosis by 4–8 years. Overdiagnosis or detection of non-progressive tumours may contribute substantially to the lead-time.