Reduction In Cancer-specific Mortality Research Articles

Strong association between reduction of late-stage cancers and reduction of cancer-specific mortality in meta-regression of randomized screening trials across multiple cancer types.

Late-stage cancer incidence has been proposed as an early surrogate for mortality in randomized controlled trials (RCTs) of cancer screening; however, its validity has not been systematically evaluated across screening RCTs of different cancers. We conducted a meta-regression analysis of cancer screening RCTs that reported both late-stage cancer incidence and cancer mortality. Based on a systematic literature review, we included 33 RCTs of screening programs targeting seven cancer types, including lung (n = 12), colorectal (n = 8), breast (n = 5), and prostate (n = 4), among others. We regressed the relative reduction of cancer mortality on the relative reduction of late-stage cancer incidence, inversely weighted for each RCT by the variance of estimated mortality reduction. Across cancer types, the relative reduction of late-stage cancer incidence was linearly associated with the relative reduction of cancer mortality. Specifically, we observed this association for lung (R2 = 0.79 and 0.996 in three recent large trials), breast (R2 = 0.94), prostate (R2 = 0.98), and colorectal cancer (R2 = 0.75 for stage III/IV cancers and 0.93 for stage IV cancers). Trials with a 20% or greater reduction in late-stage cancers were more likely to achieve a significant reduction in cancer mortality. Our results also showed that no reduction of late-stage cancer incidence was associated with no or minimal reduction in cancer mortality. Meta-regression of historical screening RCTs showed a strong linear association between reductions in late-stage cancer incidence and cancer mortality.

Survival benefit of radical prostatectomy in patients with advanced TURP-diagnosed prostate cancer: a population-based real-world study

ObjectivesA considerable number of patients are diagnosed with prostate cancer (PCa) by transurethral resection of the prostate (TURP). We aimed to evaluate whether radical prostatectomy (RP) brings survival benefits for these patients, especially in the elderly with advanced PCa.Patients and methodsWe used the Surveillance, Epidemiology, and End Results (SEER) database to obtain PCa cases diagnosed with TURP. After the propensity matching score (PSM) for case matching, univariate, multivariate, and subgroup analyses were performed to investigate whether RP impacts the survival benefit.Results4,677 cases diagnosed with PCa by TURP from 2010 to 2019 were obtained, including 1,313 RP patients and 3,364 patients with no RP (nRP). 9.6% of RP patients had advanced PCa. With or without PSM, cancer-specific mortality (CSM) and overall mortality (OM) were significantly reduced in the RP patients compared to the nRP patients, even for older (> 75 ys.) patients with advanced stages (all p < 0.05). Except for RP, younger age (≤ 75 ys.), being married, and earlier stage (localized) contributed to a significant reduction of CSM risk (all p < 0.05). These survival benefits had no significant differences among patients of different ages, married or single, and at different stages (all p for interaction > 0.05).ConclusionsBased on this retrospective population-matched study, we first found that in patients diagnosed with PCa by TURP, RP treatment may lead to a survival benefit, especially a reduction in CSM, even in old aged patients (> 75 ys.) with advanced PCa.

Cancer Stage Compared With Mortality as End Points in Randomized Clinical Trials of Cancer Screening

Randomized clinical trials of cancer screening typically use cancer-specific mortality as the primary end point. The incidence of stage III-IV cancer is a potential alternative end point that may accelerate completion of randomized clinical trials of cancer screening. To compare cancer-specific mortality with stage III-IV cancer as end points in randomized clinical trials of cancer screening. This meta-analysis included 41 randomized clinical trials of cancer screening conducted in Europe, North America, and Asia published through February 19, 2024. Data extracted included numbers of participants, cancer diagnoses, and cancer deaths in the intervention and comparison groups. For each clinical trial, the effect of screening was calculated as the percentage reduction between the intervention and comparison groups in the incidence of participants with cancer-specific mortality and stage III-IV cancer. Randomization to a cancer screening test or to a comparison group in a clinical trial of cancer screening. End points of cancer-specific mortality and incidence of stage III-IV cancer were compared using Pearson correlation coefficients with 95% CIs, linear regression, and fixed-effects meta-analysis. The included randomized clinical trials tested benefits of screening for breast (n = 6), colorectal (n = 11), lung (n = 12), ovarian (n = 4), prostate (n = 4), and other cancers (n = 4). Correlation between reductions in cancer-specific mortality and stage III-IV cancer varied by cancer type (I2 = 65%; P = .02). Correlation was highest for trials that screened for ovarian (Pearson ρ = 0.99 [95% CI, 0.51-1.00]) and lung (Pearson ρ = 0.92 [95% CI, 0.72-0.98]) cancers, moderate for breast cancer (Pearson ρ = 0.70 [95% CI, -0.26 to 0.96]), and weak for colorectal (Pearson ρ = 0.39 [95% CI, -0.27 to 0.80]) and prostate (Pearson ρ = -0.69 [95% CI, -0.99 to 0.81]) cancers. Slopes from linear regression were estimated as 1.15 for ovarian cancer, 0.75 for lung cancer, 0.40 for colorectal cancer, 0.28 for breast cancer, and -3.58 for prostate cancer, suggesting that a given magnitude of reduction in incidence of stage III-IV cancer produced different magnitudes of change in incidence of cancer-specific mortality (P for heterogeneity = .004). In randomized clinical trials of cancer screening, incidence of late-stage cancer may be a suitable alternative end point to cancer-specific mortality for some cancer types, but is not suitable for others. These results have implications for clinical trials of multicancer screening tests.

Abstract 1265: Comparison of mortality- vs. stage-based endpoints in randomized trials of cancer screening: A systematic review with implications for multi-cancer screening trials

Abstract Background: Randomized controlled trials (RCTs) assessing the endpoint of late-stage cancer incidence, rather than the gold-standard of cancer-specific mortality, are proposed for evaluation of multi-cancer early detection tests. Methods: We conducted a systematic review to assess whether stage-based endpoints can provide a valid alternative for mortality-based endpoints (registration: PROSPERO CRD42023411132). We searched PubMed to identify RCTs of cancer screening interventions published in English before January 20, 2023. Inclusion required that RCTs report, by study arm, numbers of cancer-specific deaths and cancer cases distinguishable between stages I-II vs. III-IV. Data extraction was done by 2 separate reviewers and included the numbers of cancer cases, deaths, and participants by study arm. For each trial, we calculated the percentage reduction in the cumulative (a) late-stage cancer incidence and (b) cancer-specific mortality between the intervention and control arms. We compared these two endpoints based on Pearson correlation coefficients, fixed-effects meta-analysis, and binary statistical significance. Results: We analyzed 41 trials ranging in size from 2,500 to 409,000 participants. Correlation between the reduction in cancer-specific mortality vs. stage III-IV cancer was strong for lung (Pearson’s ρ=0.92, n=12), breast (ρ=0.70, n=6), and ‘other’ cancers (ρ=0.69, n=8) but weak for colorectal (ρ=0.39, n=11) and prostate cancers (ρ&amp;lt;0, n=4). The overall correlation by fixed-effects meta-analysis across cancer types was 0.71 (95%CI=0.47-0.86) (I2=0.55). In larger trials, there was a smaller deviation between the observed reduction in cancer-specific mortality and that predicted, by cancer type, based on the trial’s reduction in stage III-IV cancer (p=0.02). Of 12 trials demonstrating a statistically significant reduction in stage III-IV cancer incidence (p&amp;lt;0.05), 5 also showed reduced cancer-specific mortality (42%). Conclusions: In screening RCTs, reductions in late-stage cancer vs. cancer-specific mortality are correlated, but with important differences by cancer type. Screening interventions that reduce late-stage cancer incidence do not necessarily reduce cancer-specific mortality. Citation Format: Xiaoshuang Feng, Hana Zahed, Justina Onwuka, Mattias Johansson, Ruth Etzioni, Matthew E. Callister, Hilary A. Robbins. Comparison of mortality- vs. stage-based endpoints in randomized trials of cancer screening: A systematic review with implications for multi-cancer screening trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1265.

Identifying disparities in brachytherapy delivery for locally advanced cervical cancer

IntroductionThe standard of care for locally advanced cervical cancer is concurrent chemotherapy and external beam radiation therapy (EBRT) followed by a brachytherapy boost. Some studies show a decreased usage of brachytherapy in cervical cancer patients despite the standard of care and known survival advantage. This study aims to characterize the utilization of brachytherapy in Oregon and identify where disparities in treatment may exist. MethodsThe Oregon State Cancer Registry database was used to identify patients diagnosed with FIGO Stage IB2-IVB cervical cancer between 2007 and 2016. Patients who received initial EBRT were categorized by whether they received brachytherapy boost or not. Age at diagnosis, county of patient residence, rural-urban status of the county, race/ethnicity, and insurance payer were studied using multivariable logistic regression to identify possible underserved populations. Survival data was compared using a Cox proportional hazard survival model. Results401 patients who received primary EBRT for FIGO stage IB2-IVB cervical cancer were identified in the 10-year span. Breakdown by stage is: 16% stage IB2, 23.9% stage II, 37.4% stage III, and 22.7% stage IV. Of those, 154 (38.4%) received brachytherapy boost treatment, 75 (18.7%) received a different boost modality, and 42.9% received no boost. Stage IV (p = 0.001) and uninsured patients (p = 0.04) were significantly less likely to receive brachytherapy. Older age was also associated with decreased brachytherapy usage, as each additional year of life decreased brachytherapy receipt by 1.8% (p = 0.04). Native American and Pacific Islander patients were the only group significantly more likely to receive brachytherapy (p=0.003). There was no significant difference in the rate of brachytherapy boost identified based on urban/rural status of the county (p = 0.63 to 0.69), other racial/ethnic categories (p = 0.66 to 0.80), or among the other stages (p=0.45 to 0.63). In Cox proportional hazard survival analysis, patients that received brachytherapy showed a 42% reduction in risk of cancer specific mortality, though this did not reach the predetermined level of statistical significance (p = 0.057). ConclusionsThe brachytherapy boost rate among locally advanced cervical cancer patients was 38.4%. The data also indicated a likely reduction in cancer specific mortality in patients receiving brachytherapy. Older patients, stage IV patients, and uninsured patients were less likely to receive brachytherapy. Given the low overall brachytherapy usage, these data indicate access and delivery of brachytherapy care needs to be improved across the state. The increased brachytherapy use in the American Indian and Pacific Islander patient population should be further studied to identify facilitators to treatment completion and potentially extrapolate to other groups.

GSOR15 Presentation Time: 11:40 AM: Underutilization of Brachytherapy: A Retrospective State Level Analysis of Brachytherapy Delivery in Locally Advanced Cervical Cancer

<h3>Purpose</h3> The standard of care for locally advanced cervical cancer is concurrent chemotherapy and external beam radiation therapy (EBRT) followed by a brachytherapy boost. Decreased rate of brachytherapy in cervical cancer patients has shown a declining survival for these patients. This study aims to characterize the utilization of brachytherapy in Oregon in order to better understand how care delivery can be improved. <h3>Materials and Methods</h3> The Oregon State Cancer Registry database was used to identify patients diagnosed with FIGO 2008 Stage IB2-IVB cervical cancer between 2007 and 2016. Patients who received initial EBRT were categorized by whether they received brachytherapy boost or not. Age at diagnosis, county, rural/urban status of the county, race/ethnicity, and insurance payer were studied using multivariable logistic regression to identify possible underserved populations. Survival data was compared using a Cox proportional hazard survival model. Changes in brachytherapy use over time were also examined by grouping patients by year of diagnosis and comparing the rates of brachytherapy utilization over the duration of the study. <h3>Results</h3> 401 patients who received primary EBRT for FIGO stage IB2-IVB cervical cancer were identified in the 10-year span. Breakdown by stage is: 16% stage IB2, 23.9% stage II, 37.4% stage III, and 22.7% stage IV. Of those, 154 (38.4%) received brachytherapy boost treatment, 75 (18.7%) received a different boost modality, and 172 (42.9%) received no boost. Stage IV (p=0.001) and uninsured patients (p=0.04) were significantly less likely to receive brachytherapy. Older age was also associated with decreased brachytherapy usage, as each additional year of life correlated with a decreased likelihood of brachytherapy receipt of 1.8% (p=0.04). Native American and Pacific Islander patients were the only group significantly more likely to receive brachytherapy (p=0.003). There was no significant difference in the rate of brachytherapy boost based on urban/rural status of the county (p=0.63 to 0.69), other racial/ethnic categories (p=0.66 to 0.80), or among the other stages (p=0.45 to 0.63). In Cox proportional hazard survival analysis, patients that received brachytherapy showed a 42% reduction in risk of cancer specific mortality, though this did not reach the level of statistical significance (p=0.057). In terms of brachytherapy utilization by year, no definitive trend was shown. Yearly rates varied from 25% to 52%, with a dip in utilization in 2013 and 2014 at around 30% before a jump in utilization in 2015 and 2016 to around 50%. <h3>Conclusions</h3> The brachytherapy boost rates among locally advanced cervical cancer patients were 38.4%. Though not statistically significant, a reduction in cancer specific mortality in patients receiving brachytherapy by 42% was seen. Older patients, stage IV patients, and uninsured patients were less likely to receive brachytherapy. Given the low overall brachytherapy usage, these data may indicate barriers to access and delivery of brachytherapy care. The increased brachytherapy use in the American Indian and Pacific Islander patient population should be further studied to identify facilitators to treatment completion and potentially extrapolate to other groups.

Identifying Disparities in Cervical Cancer Brachytherapy Delivery

<h3>Purpose/Objective(s)</h3> The standard of care for locally advanced cervical cancer is concurrent chemotherapy and external beam radiation therapy (EBRT) followed by a brachytherapy boost. Some studies show a decreased usage of brachytherapy in cervical cancer patients despite the standard of care and known survival advantage. This study aims to characterize the utilization of brachytherapy in Oregon and identify where disparities in treatment may exist. <h3>Materials/Methods</h3> The Oregon State Cancer Registry database was used to identify patients diagnosed with FIGO Stage IB2-IVB cervical cancer between 2007 and 2016. Patients who received initial EBRT were categorized by whether they received brachytherapy boost or not. Age at diagnosis, county, rural/urban status of the county, race/ethnicity, and insurance payer were studied using multivariable logistic regression to identify possible underserved populations. Survival data was compared using a Cox proportional hazard survival model. <h3>Results</h3> 401 patients who received primary EBRT for FIGO stage IB2-IVB cervical cancer were identified in the 10-year span. Breakdown by stage is: 16% Stage IB2, 23.9% stage II, 37.4% stage III, and 22.7% stage IV. Of those, 154 (38.4%) received brachytherapy boost treatment, 75 (18.7%) received a different boost modality, and 42.9% received no boost. Stage IV (p=0.001) and uninsured patients (p=0.04) were significantly less likely to receive brachytherapy. Older age was also associated with decreased brachytherapy usage, as each additional year of life decreased brachytherapy receipt by 1.8% (p=0.04). Native American and Pacific Islander patients were the only group significantly more likely to receive brachytherapy (p=0.003). There was no significant difference in the rate of brachytherapy boost identified based on urban/rural status of the county (p=0.63 to 0.69), other racial/ethnic categories (p=0.66 to 0.80), or among the other stages (p=0.45 to 0.63). In Cox proportional hazard survival analysis, patients that received brachytherapy showed a 42% reduction in risk of cancer specific mortality, though this did not reach the level of statistical significance (p=0.057). <h3>Conclusion</h3> The brachytherapy boost rates among locally advanced cervical cancer patients were 38.4%, similar to national averages. Though not statistically significant, data also showed a reduction in cancer specific mortality in patients receiving brachytherapy. Older patients, stage IV patients, and uninsured patients were less likely to receive brachytherapy. Given the low overall brachytherapy usage, these data indicate access and delivery of brachytherapy care needs to be improved across the state. The increased brachytherapy use in the American Indian and Pacific Islander patient population should be further studied to identify facilitators to treatment completion and potentially extrapolate to other groups.

Systematic review of the cost-effectiveness of screening for lung cancer with low dose computed tomography

ObjectivesLung cancer (LC) remains a burden for patients and healthcare systems, with most cases only diagnosed once disease is late stage. Screening for LC with low-dose computed tomography (LDCT) has shown a stage shift and led to a lung cancer-specific mortality reduction. Economic evaluations have been conducted which explore the benefits and costs of screening, however, previous systematic reviews concluded results were heterogeneous. LC screening has evolved and there have been further cost-effectiveness analyses conducted.The aim of this study was to provide an up-to-date systematic review of the cost-effectiveness of LC screening with LDCT. Methods and MaterialsDatabases were searched for full papers published in English 01/1994–02/2022. Inclusion criteria was full economic evaluation of LC screening using LDCT compared to either no screening or chest X-ray. ResultsForty-five evaluations were identified, three conducted alongside trials and 42 modelling studies. Thirty-nine evaluations (86.7%) found LC screening with LDCT to be cost-effective. Several findings were broadly consistent across studies: cost-effectiveness was optimal in those age 55–75 years and smoking history of at least 20 pack-years. Biennial screening was often more cost-effective than annual screening and would likely result in less additional findings and radiation exposure. A smoking cessation intervention alongside screening improved cost-effectiveness, but which intervention was optimal was unclear. Risk predictions models using more parameters to target participants for screening did not have more benefits than those using age and smoking alone, and cost-effectiveness was equivalent. Cost-effectiveness was sensitive to cost and specificity of LDCT, and disutility associated with screening. ConclusionOverall, LC screening with LDCT is cost-effective in a high-risk population. Questions remain regarding risk prediction models, smoking cessation interventions and appropriateness of utility values in the screened population. Once these uncertainties are addressed, further economic evaluation may be required to inform policymakers prior to implementation.

A Cost-Effectiveness Analysis of Lung Cancer Screening With Low-Dose Computed Tomography and a Diagnostic Biomarker.

BackgroundThe Lung Computed Tomography Screening Reporting and Data System (Lung-RADS) reduces the false-positive rate of lung cancer screening but introduces prolonged periods of uncertainty for indeterminate findings. We assess the cost-effectiveness of a screening program that assesses indeterminate findings earlier via a hypothetical diagnostic biomarker introduced in place of Lung-RADS 3 and 4A guidelines.MethodsWe evaluated the performance of the US Preventive Services Task Force (USPSTF) recommendations on lung cancer screening with and without a hypothetical noninvasive diagnostic biomarker using a validated microsimulation model. The diagnostic biomarker assesses the malignancy of indeterminate nodules, replacing Lung-RADS 3 and 4A guidelines, and is characterized by a varying sensitivity profile that depends on nodules' size, specificity, and cost. We tested the robustness of our findings through univariate sensitivity analyses.ResultsA lung cancer screening program per the USPSTF guidelines that incorporates a diagnostic biomarker with at least medium sensitivity profile and 90% specificity, that costs $250 or less, is cost-effective with an incremental cost-effectiveness ratio lower than $100 000 per quality-adjusted life year, and improves lung cancer-specific mortality reduction while requiring fewer screening exams than the USPSTF guidelines with Lung-RADS. A screening program with a biomarker costing $750 or more is not cost-effective. The health benefits accrued and costs associated with the screening program are sensitive to the disutility of indeterminate findings and specificity of the biomarker, respectively.ConclusionsLung cancer screening that incorporates a diagnostic biomarker, in place of Lung-RADS 3 and 4A guidelines, could improve the cost-effectiveness of the screening program and warrants further investigation.

A risk-based framework for assessing real-time lung cancer screening eligibility that incorporates life expectancy and past screening findings.

Current lung cancer risk-based screening approaches use a single risk-threshold, disregard life-expectancy, and ignore past screening findings. We address these limitations with a comprehensive analytical framework, the individualized lung cancer screening decision (ENGAGE) tool that aims to optimize lung cancer screening for US ever-smokers under dynamic risk assessment by incorporating life expectancy and past screening findings over time. ENGAGE employs a partially observable Markov decision process framework that integrates published risk prediction and disease progression models, to dynamically assess the trade-off between the expected health benefits and harms associated with screening. ENGAGE evaluates lung cancer risk annually and provides real-time screening eligibility that maximizes the expected quality-adjusted life-years (QALYs) of ever-smokers. We compare ENGAGE against the 2013 U.S. Preventive Services Task Force (USPSTF) lung cancer screening guideline and single-threshold risk-based screening paradigms. Compared with the 2013 USPSTF guidelines, ENGAGE expands screening coverage among ever-smokers (ENGAGE: 78%, USPSTF: 61%), while reducing the number of screening examinations per person (ENGAGE:10.43, USPSTF:12.07, P<.001), yields higher effectiveness in terms of increased lung cancer-specific mortality reduction (ENGAGE: 19%, USPSTF: 15%, P<.001) and improves screening efficiency (ENGAGE: 696, USPSTF: 819 screens per death avoided, P<.001). When compared against a single-threshold risk-based screening strategy, ENGAGE increases QALY requiring 30% fewer screens per death avoided (ENGAGE: 696, single-threshold: 889, P<.001), and reduces false positives by 40%. ENGAGE provides a comprehensive framework for dynamic risk-based assessment of lung cancer screening eligibility by incorporating life expectancy and past screening findings that can serve to guide future policies on the effectiveness and efficiency of screening. A novel decision-analytical screening framework was developed for lung cancer, the individualized lung cancer screening decision (ENGAGE) tool to provide personalized screening schedules for ever-smokers. ENGAGE captures the dynamic nature of lung cancer risk and incorporates life expectancy into the screening decision-making process. ENGAGE integrates past screening findings and changes in smoking behavior of individuals and provides informed screening decisions that outperform existing screening guidelines and single-threshold risk-based screening approaches. A personalized lung cancer screening program facilitated by a tool such as ENGAGE could enhance the efficiency of lung cancer screening.

Office-Based Renal Tumor Biopsy: a Paradigm Change in the Management of a Small Renal Mass?

The goal of this paper is to evaluate the use of an office-based renal mass biopsy (RMB), whose feasibility could represent a paradigm shift in clinical practice. Despite the earlier diagnosis of patients with renal masses, the lack of evidence showing a reduction in cancer-specific mortality warrants an examination in treatment practices. RMB is underutilized when compared to biopsy practice for all other neoplasms in every other solid organ (except testis), and the majority of RMB performed are outsourced to interventional radiologists. Performing an ultrasound-guided, office-based RMB is safe, reproducible, and has a meaningful impact on management decisions. The use of percutaneous RMB in clinical practice is growing, and the use of RMB has meaningful impact on management decisions for renal masses. Incorporating ultrasound-guided biopsy of a renal mass into clinical practice is feasible, and in contemporary practice, the urologist has the skill set to perform the procedure reliably, with low morbidity, and with minimal patient discomfort.

Does adherence to lipid-lowering medications improve cancer survival? A nationwide study of breast and colorectal cancer, and melanoma.

Inconclusive findings of lipid-lowering medications (LLMs) on cancer survival benefit require more evidence. We tested the hypothesis that adherence to this drug is associated with reduced cancer-specific mortality in a homogeneous population who had used this drug before cancer diagnosis. The Australian Cancer Database was linked to the Pharmaceutical Benefits Scheme database, and to the National Death Index (up to 2015). Medication adherence was calculated by proportion of days covered. Cox regression models with time-varying covariates were used to derive multivariable-adjusted cause-specific hazard ratio (HR) and 95% confidence interval (CI) for the associations between adherence to LLMs, statins, lipophilic, and hydrophilic statins and cancer-specific mortality. From 2003 to 2013, 3 separate cohorts of 20 046, 11 719 and 6430 female patients with newly diagnosed breast, colorectal cancer, and melanoma respectively were identified. The 1-year adherence was similar at 1-year prediagnosis in the 3 cohorts, on average 82%. Each 10% increase in 1-year adherence to LLMs was inversely associated with cancer-specific mortality among women with breast cancer (fully adjusted HR = 0.92, 95% CI 0.91-0.93), colorectal cancer (fully adjusted HR = 0.92, 95% CI 0.91-0.93), or melanoma (fully adjusted HR = 0.97, 95% CI 0.94-1.00). The reductions in cancer-specific mortality were more pronounced for women who adhered to lipophilic than hydrophilic statins in all 3 cancers albeit not statistically significant for melanoma. Among LLM users, adherence to this drug is associated with a decrease in cancer-specific mortality. If confirmed, LLMs could be considered as an adjuvant cancer therapy to improve prognosis in cancer survivors.

50P Ultrasound guided screening of gallbladder cancer in healthy volunteers: A prospective study from Northern India

Screening leads to reduction in cancer specific mortality for breast, cervix and colon cancer. Advanced Gallbladder cancer (GBC) is the commonest malignancy in Northern India. Due to rarity in western world, it remains an orphan disease for research. It carries a dismal prognosis. We did a pilot work of screening of GBC in healthy volunteers. This is a prospective study conducted under Armed Forces Medical Research Project at Lucknow from Jun2011 till Oct2012 after ethical approval and among high risk individuals. High risk was defined as asymptomatic, age ≥50 years and residents in Uttar Pradesh or Bihar. Volunteers residing in this region for < 5 years excluded. Screening was done with Ultrasound. Volunteers with irregular or focal wall thickening were considered for radical cholecystectomy. Established cases were taken as control (C-GBC). Written informed consent was obtained for all participants. Demographics were studied and survival was compared with C-GBC patients. A total of 778 volunteers were screened for GBC. Four cases of GBC were detected (S-GBC). There were 3 females and 1 male among S-GBC patients (M: F:3: 1) and 87 males and 32 females (M: F:2.7 :1) in C-GBC cases. S-GBC patients had early stage of diagnosis (p= 0.001) as compared to C-GBC. All four cases underwent curative radical cholecystectomy compared to 18.8 % in C-GBC cases (p= 0.004). Median overall survival (mOS) not reached and 09 months in S-GBC and C-GBC (p= 0.0453), respectively. This pilot work established the proof of principle of screening for GBC, leading to early detection, ensures surgical resection and improved overall survival. This finding must be studied in future larger longitudinal studies.

A discussion on controversies and ethical dilemmas in prostate cancer screening

Prostate cancer (PCa) is one of the the most common cancers in men. A blood test called prostate-specific antigen (PSA) has a potential to pick up this cancer very early...

Lung cancer screening knowledge in four internal medicine university programs.

11027 Background: Low density CT (LDCT) screening reduces lung cancer specific and all-cause mortality in high risk populations. However, it remains underutilized. Screening discussions often start in primary care clinics of which nearly 30% are occupied by residents. Recognizing gaps in knowledge in early medical training may translate into a higher utilization of LDCT screening. Methods: To evaluate knowledge about lung cancer screening in Internal Medicine (IM) residents at 4 academic programs we distributed a survey to assess population at risk, mortality benefits, comparison between LDCT, colonoscopy and mammogram, and a knowledge self assessment. Results: 166 out of 360 (46%) IM residents at the 4 institutions participated, including 42% PGY-1, 30% PGY-2, and 28% PGY-3. Residents attained an average of 2.9 correct responses out of 7 (43.1%), without any statistically significant difference among programs. PGY-1 residents performed better than PGY-2 and PGY-3 (p=0.022). 36% correctly identified the appropriate population for screening. 90% correctly indicated that LDCT screening results in a cancer specific mortality reduction. 59% correctly indicated that LDCT results in all-cause mortality reduction. 7.7% answered that women stand to benefit the most from screening. 66% correctly answered that LDCT underperforms colonoscopy regarding mortality reduction. 22% answered correctly that LDCT outperforms mammography in reducing mortality. 65% of residents perceived their knowledge to be average or lower. Conclusions: LDCT knowledge is deficient among the residents studied. PGY-1 residents performed significantly better than their upper level peers. There were no significant differences among institutions. [Table: see text]

Trimodality therapy for HPV-positive oropharyngeal cancer: A population-based study: Trimodality therapy for HPV+ OPC

BackgroundAlthough HPV status is a well-established prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC), approximately 20% of HPV-positive patients die from their disease. We therefore sought to ascertain whether there is a benefit to trimodality therapy with surgery among patients with locally advanced (LA) disease receiving chemoradiation. MethodsThe SEER Head and Neck with HPV Status Database identified adult patients with non-metastatic OPSCC between 2013 and 2014 with known HPV status who received chemoradiation as part of definitive treatment. The primary outcome was cancer-specific mortality (CSM) for locally-advanced (LA) (T3-T4, or N2-N3, per AJCC 7) versus early-stage (ES) (T1-T2 and N0-N1) disease, stratified by HPV status. The secondary outcome was overall survival (OS). ResultsAmong 2974 patients who met study criteria, 671 patients (22.6%) received upfront surgery (trimodality therapy). In the LA setting, there was a significant reduction in CSM with trimodality therapy compared to chemoradiation alone in HPV-positive (Adjusted Hazard Ratio [AHR] 0.19, 95% Confidence Interval [CI] 0.04–0.80; P = 0.024), but not HPV-negative disease [Pinteraction = 0.04]. There was no benefit to trimodality therapy for ES disease, regardless of HPV status. There was also an improvement in OS with trimodality therapy for HPV-positive LA patients (AHR = 0.28, p = 0.006, 95% CI = 0.11–0.70). In contrast, trimodality therapy was not associated with improved OS for HPV-negative patients regardless of stage. ConclusionsHPV status may predict for improved outcomes with surgery/trimodality therapy in LA OPSCC. Our findings support prospective investigations to optimize care for the subset of HPV-positive patients who are at greatest risk of cancer death, where trimodality therapy may be appropriate.

All-cause mortality versus cancer-specific mortality as outcome in cancer screening trials: A review and modeling study.

BackgroundAll‐cause mortality has been suggested as an end‐point in cancer screening trials in order to avoid biases in attributing the cause of death. The aim of this study was to investigate which sample size and follow‐up is needed to find a significant reduction in all‐cause mortality.MethodsA literature review was conducted to identify previous studies that modeled the effect of screening on all‐cause mortality. Microsimulation modeling was used to simulate breast cancer, lung cancer, and colorectal cancer screening trials. Model outputs were: cancer‐specific deaths, all‐cause deaths, and life‐years gained per year of follow‐up.ResultsThere were large differences between the evaluated cancers. For lung cancer, when 40 000 high‐risk people are randomized to each arm, a significant reduction in all‐cause mortality could be expected between 11 and 13 years of follow‐up. For breast cancer, a significant reduction could be found between 16 and 26 years of follow‐up for a sample size of over 300 000 women in each arm. For colorectal cancer, 600 000 persons in each arm were required to be followed for 15‐20 years. Our systematic literature review identified seven papers, which showed highly similar results to our estimates.ConclusionCancer screening trials are able to demonstrate a significant reduction in all‐cause mortality due to screening, but require very large sample sizes. Depending on the cancer, 40 000‐600 000 participants per arm are needed to demonstrate a significant reduction. The reduction in all‐cause mortality can only be detected between specific years of follow‐up, more limited than the timeframe to detect a reduction in cancer‐specific mortality.

Structured Population-based Prostate-specific Antigen Screening for Prostate Cancer: The European Association of Urology Position in 2019

Prostate cancer (PCa) is one of the first three causes of cancer mortality in Europe. Screening in asymptomatic men (aged 55–69yr) using prostate-specific antigen (PSA) is associated with a migration toward lower staged disease and a reduction in cancer-specific mortality. By 20yr after testing, around 100 men need to be screened to prevent one PCa death. While this ratio is smaller than for breast and colon cancer, the long natural history of PCa means many men die from other causes. As such, the nonselective use of PSA testing and radical treatments can lead to overdiagnosis and overtreatment. The European Association of Urology (EAU) supports measures to encourage appropriate PCa detection through PSA testing, while reducing overdiagnosis and overtreatment. These goals may be achieved using personalized risk-stratified approaches. For diagnosis, the greatest benefit from early detection is likely to come in men assessed using baseline PSA levels at the age of 45yr to individualize screening intervals. Multiparametric magnetic resonance imaging as well as risk calculators based on family history, ethnicity, digital rectal examination, and prostate volume should be considered to triage the need for biopsy, thus reducing the risk of overdiagnosis. For treatment, the EAU advocates balancing patient's life expectancy and cancer's mortality risk when deciding an approach. Active surveillance is encouraged in well-informed patients with low-risk and some intermediate-risk cancers, as it decreases the risks of overtreatment without compromising oncological outcomes. Conversely, the EAU advocates radical treatment in suitable men with more aggressive PCa. Multimodal treatment should be considered in locally advanced or high-grade cancers. Patient summaryImplementation of prostate-specific antigen (PSA)-based screening should be considered at a population level. Men at risk of prostate cancer should have a baseline PSA blood test (eg, at 45yr). The level of this test, combined with family history, ethnicity, and other factors, can be used to determine subsequent follow-up. Magnetic resonance imaging scans and novel biomarkers should be used to determine which men need biopsy and how any cancers should be treated.

Cancer overdiagnosis: a biological challenge and clinical dilemma.

For cancer screening to be successful, it should primarily detect cancers with lethal potential or their precursors early, leading to therapy that reduces mortality and morbidity. Screening programmes have been successful for colon and cervical cancers, where subsequent surgical removal of precursor lesions has resulted in a reduction in cancer incidence and mortality. However, many types of cancer exhibit a range of heterogeneous behaviours and variable likelihoods ofprogression and death. Consequently, screening for some cancers may have minimal impact on mortality and may do more harm than good. Since the implementation of screening tests for certain cancers (for example, breast and prostate cancers), a spike in incidence of in situ and early-stage cancers has been observed, but a link to reduction in cancer-specific mortality has not been as clear. It is difficult to determine how many of these mortality reductions are due to screening and how many are due to improved treatments of tumours. In cancers with lower incidence but high mortality (for example, pancreatic cancer), screening has focused on high-risk populations, but challenges similar to those for general population screening remain, particularly with regard to finding lesions with difficult-to-characterize malignant potential (for example, intraductal papillary mucinous neoplasms). More sensitive screening methods are detecting smaller and smaller lesions, but this has not been accompanied by a comparable reduction in the incidence of invasive cancers. In this Opinion article, we focus on the contribution of screening in general and high-risk populations to overdiagnosis, the effects of overdiagnosis on patients and emerging strategies to reduce overdiagnosis of indolent cancers through an understanding of tumour heterogeneity, the biology of how cancers evolve and progress, the molecular and cellular features of early neoplasia and the dynamics of the interactions of early lesions with their surrounding tissue microenvironment.

The impact of intraductal carcinoma of the prostate on the site and timing of recurrence and cancer‐specific survival

To investigate the effect of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens in the context of the site of recurrence, time to recurrence, and cancer-specific survival in two academic cohorts of locally, regionally, or distantly recurrent prostate cancer. Our cohort included men enrolled into two academic tissue repositories from 1993 to 2011, who were treated with first-line RP who later experienced local recurrence, regional recurrence, or distant metastasis (together termed clinical recurrence, CR). RP material was reviewed to identify IDC-P and to update grading to current standards. The primary endpoint was the initial location of CR. Secondary endpoints included time to CR and cancer-specific survival. Pearson's chi-square, Welch's t-test, Mann-Whitney U test and Fisher's exact test were performed for univariate analyses. Multinomial logistic regression was used for multivariate analyses. Cancer-specific survival was analyzed with the generalized Wilcoxon test and Cox regression. Eighty-five patients with CR were included in the analysis. IDC-P was present in 78.5% of patients from Center 1 and 70.0% from Center 2 (P = 0.547). IDC-P was independently associated with distant metastasis at initial CR (multivariate odds ratio = 6.27, P = 0.015). IDC-P status did not affect time to recurrence; median survival without recurrence was at 53 months for IDC-P(+) and at 50 months for IDC-P(-) (P = 0.441). Distant metastases at the initial CR event had a 36% reduction of cancer-specific survival compared to local recurrences (P = 0.007). Additionally, prostatic-bed radiotherapy (adjuvant or salvage for biochemical recurrence before distant metastasis) was associated with a 25% reduction in cancer-specific mortality compared to no radiotherapy (P = 0.023). Similar reduction in cancer-specific mortality was observed in the subgroup of patients with distant metastasis and IDC-P when treated with radiotherapy (29%, P = 0.050). In our cohort, presence of IDC-P was an independent factor for distant metastasis at initial CR, but did not have a significant impact on time to CR. Furthermore, metastatic patients showed statistically reduced cancer-specific mortality when treated with radiotherapy. This reduction in cancer-specific mortality was also identified in patients with IDC-P. Future large scale validation studies should take into account the presence of IDC-P and confirm its impact on disease progression.