Screen-detected vs symptomatic breast cancer: is improved survival due to stage migration alone?
Ontology highlight
ABSTRACT: This paper examines whether screen-detected breast cancer confers additional prognostic benefit to the patient, over and above that expected by any shift in stage at presentation. In all, 5604 women (aged 50-70 years) diagnosed with invasive breast cancer between 1998 and 2003 were identified by the Eastern Cancer Registration and Information Centre (ECRIC) and mammographic screening status was determined. Using proportional hazards regression, we estimated the effect of screen detection compared with symptomatic diagnosis on 5-year survival unadjusted, then adjusted for age and Nottingham Prognostic Index (NPI). A total of 72% of the survival benefit associated with screen-detected breast cancer can be accounted for by age and shift in NPI. Survival analysis by continuous NPI showed a small but systematic survival benefit for screen-detected cancers at each NPI value. These data show that although most of the screen-detected survival advantage is due to a shift in NPI, the mode of detection does impact on survival in patients with equivalent NPI scores. This residual survival benefit is small but significant, and is likely to be due to differences in tumour biology. Current prognostication tools may, therefore, overestimate the benefit of systemic treatments in screen-detected cancers and lead to overtreatment of these patients.
Project description:BackgroundSeveral recent studies have shown that screen detection remains an independent prognostic factor after adjusting for disease stage at presentation. This study compares the molecular characteristics of screen-detected with symptomatic breast cancers to identify if differences in tumour biology may explain some of the survival benefit conferred by screen detection.MethodsA total of 1379 women (aged 50-70 years) with invasive breast cancer from a large population-based case-control study were included in the analysis. Individual patient data included tumour size, grade, lymph node status, adjuvant therapy, mammographic screening status and mortality. Immunohistochemistry was performed on tumour samples using 11 primary antibodies to define five molecular subtypes. The effect of screen detection compared with symptomatic diagnosis on survival was estimated after adjustment for grade, nodal status, Nottingham Prognostic Index (NPI) and the molecular markers.ResultsFifty-six per cent of the survival benefit associated with screen-detected breast cancer was accounted for by a shift in the NPI, a further 3-10% was explained by the biological variables and more than 30% of the effect remained unexplained.ConclusionCurrently known biomarkers remain limited in their ability to explain the heterogeneity of breast cancer fully. A more complete understanding of the biological profile of breast tumours will be necessary to assess the true impact of tumour biology on the improvement in survival seen with screen detection.
Project description:ImportanceThe nationwide fecal immunochemical test-based screening program has influenced surgical care for patients with colorectal cancer (CRC) in the Netherlands, although these implications have not been studied in much detail so far.ObjectiveTo compare surgical outcomes of patients diagnosed as having CRC through the fecal immunochemical test-based screening program (screen detected) and patients with non-screen-detected CRC.Design, setting, and participantsThis was a population-based comparative cohort study using the Dutch ColoRectal Audit and analyzed all Dutch hospitals performing CRC resections. Patients who underwent elective resection for CRC between January 2011 to December 2016 were included.InterventionsColorectal cancer surgery.Main outcomes and measuresPostoperative nonsurgical complications, postoperative surgical complications, postoperative 30-day or in-hospital mortality, and complicated course (postoperative complication resulting in a hospital stay >14 days and/or a reintervention and/or mortality). A risk-stratified comparison was made for different postoperative outcomes based on screening status (screen detected vs not screen detected), cancer stage (I-IV), and for cancer stage I to III also on age (aged ≤70 years and >70 years) and American Society of Anesthesiologists score (I-II and III-IV). To determine any residual case-mix-corrected differences in outcomes between patients with screen-detected and non-screen-detected cancer, univariable and multivariable logistic regression analyses were performed.ResultsIn total, 36 242 patients with colon cancer and 17 416 patients with rectal cancer were included for analysis. Compared with patients with non-screen-detected CRC, screen-detected patients were younger (mean [SD] age, 68 [5] vs 70 [11] years), more often men (3777 [60%] vs 13 506 [57%]), and had lower American Society of Anesthesiologists score (American Society of Anesthesiologists score III+: 838 [13%] vs 5529 [23%]). Patients with stage I to III colon cancer who were screen detected had a significantly lower mortality and complicated course rate compared with non-screen-detected patients. For patients with rectal cancer, only a significant difference was found in mortality rate in patients with a cancer stage IV disease, which was higher in the screen-detected group. Compared with non-screen-detected colon cancer, an independent association was found for screen-detected colon cancer on nonsurgical complications (adjusted odds ratio, 0.81; 95% CI, 0.73-0.91), surgical complications (adjusted odds ratio, 0.80; 95% CI, 0.72-0.89), and complicated course (adjusted odds ratio, 0.80; 95% CI, 0.71-0.90). Screen-detected rectal cancer had significantly higher odds on mortality.Conclusions and relevancePostoperative outcomes were significantly better for patients with colon cancer referred through the fecal immunochemical test-based screening program compared with non-screen-detected patients. These differences were not found in patients with rectal cancer. The outcomes of patients with screen-detected colon cancer were still better after an extensive case-mix correction, implying additional underlying factors favoring patients referred for surgery through the screening program.
Project description:Colorectal cancers (CRCs) detected through the NHS Bowel Cancer Screening Programme (BCSP) have been shown to have a more favourable outcome compared to non-screen-detected cancers. The aim was to identify whether this was solely due to the earlier stage shift of these cancers, or whether other factors were involved.A combination of a regional CRC registry (Northern Colorectal Cancer Audit Group) and the BCSP database were used to identify screen-detected and interval cancers (diagnosed after a negative faecal occult blood test, before the next screening round), diagnosed between April 2007 and March 2010, within the North East of England. For each Dukes' stage, patient demographics, tumour characteristics, and survival rates were compared between these two groups.Overall, 322 screen-detected cancers were compared against 192 interval cancers. Screen-detected Dukes' C and D CRCs had a superior survival rate compared with interval cancers (P=0.014 and P=0.04, respectively). Cox proportional hazards regression showed that Dukes' stage, tumour location, and diagnostic group (HR 0.45, 95% CI 0.29-0.69, P<0.001 for screen-detected CRCs) were all found to have a significant impact on the survival of patients.The improved survival of screen-detected over interval cancers for stages C and D suggest that there may be a biological difference in the cancers in each group. Although lead-time bias may have a role, this may be related to a tumour's propensity to bleed and therefore may reflect detection through current screening tests.
Project description:ObjectivesThe aim of this study was to compare the morphology, radiological stage, conspicuity, and computer-assisted detection (CAD) characteristics of colorectal cancers (CRC) detected by computed tomographic colonography (CTC) in screening and symptomatic populations.MethodsTwo radiologists independently analyzed CTC images from 133 patients diagnosed with CRC in (a) two randomized trials of symptomatic patients (35 patients with 36 tumours) and (b) a screening program using fecal occult blood testing (FOBt; 98 patients with 100 tumours), measuring tumour length, volume, morphology, radiological stage, and subjective conspicuity. A commercial CAD package was applied to both datasets. We compared CTC characteristics between screening and symptomatic populations with multivariable regression.ResultsScreen-detected CRC were significantly smaller (mean 3.0 vs 4.3 cm, p < 0.001), of lower volume (median 9.1 vs 23.2 cm3, p < 0.001) and more frequently polypoid (34/100, 34 % vs. 5/36, 13.9 %, p = 0.02) than symptomatic CRC. They were of earlier stage than symptomatic tumours (OR = 0.17, 95 %CI 0.07-0.41, p < 0.001), and were judged as significantly less conspicuous (mean conspicuity 54.1/100 vs. 72.8/100, p < 0.001). CAD detection was significantly lower for screen-detected (77.4 %; 95 %CI 67.9-84.7 %) than symptomatic CRC (96.9 %; 95 %CI 83.8-99.4 %, p = 0.02).ConclusionsScreen-detected CRC are significantly smaller, more frequently polypoid, subjectively less conspicuous, and less likely to be identified by CAD than those in symptomatic patients.Key points• Screen-detected colorectal cancers (CRC) are significantly smaller than symptomatic CRC. • Screening cases are significantly less conspicuous to radiologists than symptomatic tumours. • Screen-detected CRC have different morphology compared to symptomatic tumours (more polypoid, fewer annular). • A commercial computer-aided detection (CAD) system was significantly less likely to note screen-detected CRC.
Project description:ImportanceTo date, there is no well-defined standard of care for early-stage pediatric Hodgkin lymphoma (HL), which may include chemotherapy alone or combined modality therapy (CMT) with chemotherapy followed by radiotherapy. Although the use of radiotherapy in pediatric HL is decreasing, this strategy remains controversial.ObjectiveTo examine the use of CMT in pediatric HL and its association with improved overall survival using data from a large cancer registry.Design, setting, and participantsThis observational cohort study used data from the National Cancer Database to evaluate clinical features and survival outcomes among 5657 pediatric patients (age, 0.1-21 years) who received a diagnosis of stage I or II HL in the United States from January 1, 2004, to December 31, 2015. Statistical analysis was conducted from May 1 to November 1, 2018.ExposuresPatients received definitive treatment with chemotherapy or CMT, defined as chemotherapy followed by radiotherapy.Main outcomes and measuresKaplan-Meier survival curves were used to examine overall survival. The association between CMT use, covariables, and overall survival was assessed in multivariable Cox proportional hazards regression models. Use of radiotherapy was assessed over time.ResultsAmong the 11 546 pediatric patients with HL in the National Cancer Database, 5657 patients (3004 females, 2596 males, and 57 missing information on sex; mean [SD] age, 17.1 [3.6] years) with stage I or II classic HL were analyzed. Of these patients, 2845 (50.3%) received CMT; use of CMT vs chemotherapy alone was associated with younger age (<16 years, 1102 of 2845 [38.7%] vs 856 of 2812 [30.4%]; P < .001), male sex (1369 of 2845 [48.1%] vs 1227 of 2812 [43.6%]; P < .001), stage II disease (2467 of 2845 [86.7%] vs 2376 of 2812 [84.5%]; P = .02), and private health insurance (2065 of 2845 [72.6%] vs 1949 of 2812 [69.3%]; P = .002). The 5-year overall survival was 94.5% (confidence limits, 93.8%, 95.8%) for patients who received chemotherapy alone and 97.3% (confidence limits, 96.4%, 97.9%) for those who received CMT, which remained significant in the intention-to-treat analysis and multivariate analysis (adjusted hazard ratio for CMT, 0.57; 95% CI, 0.42-0.78; P < .001). In the sensitivity analysis, the low-risk cohort (stage I-IIA) and adolescent and young adult patients had the greatest benefit from CMT (adjusted hazard ratio, 0.47; 95% CI, 0.40-0.56; P < .001). The use of CMT decreased by 24.8% from 2004 to 2015 (from 59.7% [271 of 454] to 34.9% [153 of 438]).Conclusions and relevanceIn this study, pediatric patients with early-stage HL receiving CMT experienced improved overall survival 5 years after treatment. There is a nationwide decrease in the use of CMT, perhaps reflecting the bias of ongoing clinical trials designed to avoid consolidation radiotherapy. This study represents the largest data set to date examining the role of CMT in pediatric HL.
Project description:ObjectivesWe compared the overall survival (OS) and cancer-specific survival (CSS) of patients who received radiotherapy and surgery, respectively, in a large population.MethodsIn this study, we counted the patients diagnosed with stage IA lung adenocarcinoma in the SEER database from 2015 to 2019. We compared the overall survival (OS) and cancer-specific survival (CSS) through Kaplan Meier analysis, balanced the differences of primary data through propensity score matching (PSM), screened independent prognostic factors through Cox regression analysis, and then compared the survival differences of different treatment methods through hierarchical analysis.ResultsAmong 11,159 patients with stage IA lung adenocarcinoma, 4254 patients chose radiotherapy alone (38.1%), and 6688 patients were finally included through the propensity score matching. The median survival time for patients with radiotherapy alone was 53 months, while the patients with surgery alone did not reach the median survival time (p < 0.001). Multivariate analysis showed that age, sex, tumor size, and household income affected the prognosis of patients. The results of the stratified analysis showed that, except in the subgroup of age ≤ 50 years, almost all subgroup analyses showed that surgical treatment achieved better results.ConclusionsRadiotherapy alone can be used as an option for patients with stage IA lung adenocarcinoma who cannot tolerate surgery, but the benefit to patients is limited, and surgical treatment may still be the best choice.
Project description:We hypothesized that sorafenib plus transarterial chemoembolization (TACE) would confer survival benefits over sorafenib alone for advanced hepatocellular carcinoma (aHCC). We investigated this while using the population-based All-Cancer Dataset to assemble a cohort (n = 3674; median age, 60; 83% men) of patients receiving sorafenib for aHCC (Child-Pugh A) with macro-vascular invasion or nodal/distant metastases. The patients were classified into the sorafenib-TACE group (n = 426) or the propensity score-matched sorafenib-alone group (n = 1686). All of the participants were followed up until death or the end of the study. Time-dependent Cox model and the Mantel-Byar test were used for survival analysis. During the median follow-ups of 221 and 133 days for the sorafenib-TACE and sorafenib-alone groups, 164 (39%) and 916 (54%) deaths occurred, respectively; the corresponding median overall survivals (OS) were 381 and 204 days, respectively (hazard ratio, HR: 0.74; 95% confidence interval, CI, 0.63-0.88; p = 0.021). The one-year and six-month OS were 53.5% and 80.3% in the sorafenib-TACE group and 32.4% and 54.4% in the sorafenib-alone group, respectively. The major complications were comparable between the two groups. The addition of TACE to sorafenib improves survival, with a 26% reduction in mortality. These findings provide strong real-world evidence that supports this combination strategy for eligible Child-Pugh A aHCC patients.
Project description:BackgroundBreast conserving surgery (BCS) and adjuvant hormonal therapy (HT) without radiation therapy (RT) is an acceptable approach for older women with early stage, estrogen receptor (ER) positive breast cancer. Toxicity and compliance remain issues with HT. Adjuvant RT alone may have better compliance, but its efficacy in the absence of HT is unclear. We aim to assess patterns of adjuvant therapy and survival outcomes among older women with early stage, ER positive (ER+) breast cancer.MethodsThe National Cancer Data Base (NCDB) was used to identify 130,194 women age ≥65 years with invasive ER+, node negative breast cancer diagnosed between 2004 and 2015. All patients underwent BCS. Kaplan-Meier survival curves were used to examine overall survival (OS). The association between adjuvant therapy and OS was assessed in multivariable Cox proportional hazards regression models.ResultsUnadjusted 5/10-year OS rates were 90.0%/64.3% for HT and RT, 84.2%/54.9% for RT alone, 78.7%/44.5% for HT alone, and 71.6%/38.0% for no treatment; p<0.001 for all. Compared to HT alone, the 10-year multivariable hazard ratio (HR) for death for RT alone was 0.86 (95% CI 0.82-0.91). In propensity-matched patients who received RT alone or HT alone (n=21,326), RT alone had significantly better survival at 5 (HRadj : 0.84) and 10 (HRadj : 0.87) years.ConclusionsOlder women with early stage ER+ breast cancer who undergo BCS and receive both HT and RT have the best survival, while RT as single-modality therapy had higher rates of OS at 5 and 10 years compared to HT alone.
Project description:BackgroundAn increasing proportion of colorectal cancers (CRCs) are detected through screening due to the availability of organised population-based programmes. We aimed to analyse survival probabilities of patients with screen-detected CRC in European countries.MethodsData from CRC patients were obtained from 16 population-based cancer registries in nine European countries. We included patients with cancer diagnosed from the year organised CRC screening programmes were introduced until the most recent year with available data at the time of analysis, whose ages at diagnosis fell into the age groups targeted by screening. Patients were followed up with regards to vital status until 2016-2020 across the various countries. Overall and CRC-specific survival were analysed by mode of detection and stage at diagnosis for all countries combined and for each country separately using the Kaplan-Meier method.FindingsWe included data from 228 134 patients, of whom 134 597 (aged 60-69 years at diagnosis targeted by screening in all countries) were considered in analyses for all countries combined. 22·3% (38 080/134 597) of patients had cancer detected through screening. Most screen-detected cancers were found at stages I-II (65·6% [12 772/19 469 included in stage-specific analyses]), while the majority of non-screen-detected cancers were found at stages III-IV (56·4% [31 882/56 543 included in stage-specific analyses]). Five-year overall and CRC-specific survival rates for patients with screen-detected cancer were 83·4% (95% CI 82·9-83·9) and 89·2% (88·8-89·7), respectively; for patients with non-screen-detected cancer, they were much lower (57·5% [57·2-57·8] and 65·7% [65·4-66·1], respectively). The favourable survival of patients with screen-detected cancer was also seen within each stage - five-year overall survival rates for patients with screen-detected stage I, II, III, and IV cancers were 92.4% (95% CI 91·6-93·1), 87·9% (86·6-89·1), 80·7% (79·3-82·0), and 32·3 (29·4-35·2), respectively. These patterns were also consistently seen for each individual country.InterpretationPatients with cancer diagnosed at screening have a very favourable prognosis. In the rare case of detection of advanced stage cancer, survival probabilities are still much higher than those commonly reported for all patients regardless of mode of detection. Although these results cannot be taken to quantify screening effects, they provide useful and encouraging information for patients with screen-detected CRC and their physicians.FundingThis study was supported in part by grants from the German Federal Ministry of Education and Research and the German Cancer Aid.
Project description:BackgroundThe incidence of T1 colorectal cancer (CRC) has increased with the implementation of CRC screening programs. It is unknown whether the outcomes and risk models for T1 CRC based on non-screen-detected patients can be extrapolated to screen-detected T1 CRC. This study aimed to compare the stage distribution and oncologic outcomes of T1 CRC patients within and outside the screening program.MethodsData from T1 CRC patients diagnosed between 2014 and 2017 were collected from 12 hospitals in the Netherlands. The presence of lymph node metastasis (LNM) at diagnosis was compared between screen-detected and non-screen-detected patients using multivariable logistic regression. Cox proportional hazard regression was used to analyze differences in the time to recurrence (TTR), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival. Additionally, the performance of conventional risk factors for LNM was evaluated across the groups.Results1803 patients were included (1114 [62%] screen-detected), with median follow-up of 51 months (interquartile range 30). The proportion of LNM did not significantly differ between screen- and non-screen-detected patients (12.6% vs. 8.9%; odds ratio 1.41; 95%CI 0.89-2.23); a prediction model for LNM performed equally in both groups. The 3- and 5-year TTR, MFS, and CSS were similar for patients within and outside the screening program. However, overall survival was significantly longer in screen-detected T1 CRC patients (adjusted hazard ratio 0.51; 95%CI 0.38-0.68).ConclusionsScreen-detected and non-screen-detected T1 CRCs have similar stage distributions and oncologic outcomes and can therefore be treated equally. However, screen-detected T1 CRC patients exhibit a lower rate of non-CRC-related mortality, resulting in longer overall survival.