True Survival Research Articles

A novel Bayesian continuous piecewise linear log-hazard model, with estimation and inference via reversible jump Markov chain Monte Carlo.

We present a reversible jump Bayesian piecewise log-linear hazard model that extends the Bayesian piecewise exponential hazard to a continuous function of piecewise linear log hazards. A simulation study encompassing several different hazard shapes, accrual rates, censoring proportion, and sample sizes showed that the Bayesian piecewise linear log-hazard model estimated the true mean survival time and survival distributions better than the piecewsie exponential hazard. Survival data from Wake Forest Baptist Medical Center is analyzed by both methods and the posterior results are compared.

A Birnbaum-Saunders Model for Joint Survival and Longitudinal Analysis of Congestive Heart Failure Data

We consider a parametric joint modelling of longitudinal measurements and survival times, motivated by a study conducted at the Heart Institute (Incor), São Paulo, Brazil, with the objective of evaluating the impact of B-type Natriuretic Peptide (BNP) collected at different instants on the survival of patients with Congestive Heart Failure (CHF). We employ a linear mixed model for the longitudinal response and a Birnbaum-Saunders model for the survival times, allowing the inclusion of subjects without longitudinal observations. We derive maximum likelihood estimators of the joint model parameters and conduct a simulation study to compare the true survival probabilities with dynamic predictions obtained from the fit of the proposed joint model and to evaluate the performance of the method for estimating the model parameters.The proposed joint model is applied to the cohort of 1609 patients with CHF, of which 1080 have no BNP measurements. The parameter estimates and their standard errors obtained via: i) the traditional approach, where only individuals with at least one measurement of the longitudinal response are included and ii) the proposed approach, which includes survival information from all individuals, are compared with those obtained via marginal (longitudinal and survival) models.

Marine mortality in the river? Atlantic salmon smolts under high predation pressure in the last kilometres of a river monitored for stock assessment

AbstractThe River Bush (Northern Ireland) is an index river for the estimation of Atlantic salmon, Salmo salar L., stock size, population dynamics and marine survival rates. Marine survival estimates are based on the number of smolts counted at a trap 3.5 km upstream of the river outlet. The survival from release to coastal inshore waters for acoustic‐tagged smolts released at the Bushmills trap varied between 32% and 68%, with both year and brightness during river exit playing a significant role in explaining the variations in survival. This constitutes an important survival bottleneck. Contrary to true marine mortality, this significant loss of smolts in the river and nearshore environments could be reduced by focused management actions. More studies on other rivers, where smolts are enumerated above the head of tide, could further partition smolt and post‐smolt mortality, help differentiate true marine survival and help understand fluctuations in adult returns.

Growth of two Atlantic Coast Piping Plover populations

AbstractSpecies listed under the U.S. Endangered Species Act are required to meet stated recovery goals for delisting. These goals often are developed early in the species’ conservation history and may need to be updated or refined as new information becomes available. The Atlantic Coast Piping Plover (Charadrius melodus), which was listed more than 30 yr ago, has not met recovery goals through much of its range. Initial recovery goals included maintaining a reproductive output of 1.5 fledged chicks per pair for 5 yr. This goal was based on modelling that assumed equal survival rates for adults throughout the range, but recent studies suggest that demographic rates may vary with latitude. To investigate latitudinal variation, we developed demographic and population growth estimates for 2 breeding populations of Piping Plovers on the U.S. Atlantic Coast on Fire Island, New York (40.7°N), and on the Outer Banks of North Carolina (35.3°N) in 2013–2017. Breeding success (nest success and pre-fledge chick survival) varied annually but was lower in North Carolina than New York. Average adult true survival in New York (x̅ = 0.73, SE = 0.04) was similar to average survival in North Carolina (x̅ = 0.69, SE = 0.07). Annual post-fledging survival for both sites, however, was variable and often higher than had been previously reported for Atlantic Coast Piping Plovers (0.43–0.66 for New York; 0.31 and 1.0 for North Carolina). While the estimated reproductive output needed for a stationary population for both sites was similar (1.10 chicks per pair for New York, 95% CI: 0.83–1.41; 1.08 for North Carolina, 95% CI: 0.67–1.59), only the New York population achieved or exceeded these values during our study. Our findings suggest that understanding annual and latitudinal demographic variability would be helpful in refining recovery goals.

Annual survival in female white‐winged scoters and lesser scaup

ABSTRACTQuantifying survival and understanding underlying sources of variation are important for developing population models and informing management decisions. We estimated apparent survival (i.e., true survival less permanent emigration) for adult female white‐winged scoters (Melanitta fusca) and lesser scaup (Aythya affinis) breeding at a northern boreal forest site in western Canada, 2002–2008. We also evaluated variation in survival relative to indices of breeding status, individual quality, spring weather conditions, local small‐mammal abundance, and overwinter climate. Breeding female scoters had higher apparent survival than did nonbreeding females, suggesting that breeders had higher survival or fidelity to the study area, or that more nonbreeders were transient birds that may have bred elsewhere in subsequent years. Apparent survival rate for breeding female scoters was unrelated to other individual and environmental covariates. Nest‐trapped female scaup had higher apparent survival rates than did prenesting females captured in decoy traps, implying that more pre‐nesters dispersed permanently or died after marking. Nesting female scaup with higher body condition or those in years when small mammals were more abundant had higher apparent survival; associations between survival and other environmental covariates were less certain. Overall, apparent survival rate of breeding adult female scoters was lower than reported for scoters from other North American locations or for other sea duck species, whereas estimates for nesting female scaup were comparable with those from other boreal and prairie‐parkland locations. Our results indicate that for scaup in this region, factors influencing female body condition, such as maintaining high‐quality habitat, areas with abundant food or low disturbance, could improve annual survival. © The Wildlife Society, 2019

Brood Size Affects Future Reproduction in a Long-Lived Bird with Precocial Young.

Estimation of trade-offs between current reproduction and future survival and fecundity of long-lived vertebrates is essential to understanding factors that shape optimal reproductive investment. Black brant geese (Branta bernicla nigricans) fledge more goslings, on average, when their broods are experimentally enlarged to be greater than the most common clutch size of four eggs. Thus, we hypothesized that the lesser frequency of brant clutches exceeding four eggs results, at least partially, from a future reduction in survival, breeding probability, or clutch size for females tending larger broods. We used an 8-year mark-recapture data set (Barker robust design) with 5 years of clutch and brood manipulations to estimate long-term consequences of reproductive decisions in brant. We did not find evidence of a trade-off between reproductive effort and true survival or future initiation date and clutch size. Rather, future breeding probability was maximized ( [SE]) for manipulated females tending broods of four goslings and was lower for females tending smaller (one gosling; [SE]) or larger (seven goslings; [SE]) broods. Our results suggest that demographic trade-offs for female brant tending large broods may reduce the fitness value of clutches larger than four and, therefore, contribute to the paucity of larger clutches. The lack of a trade-off between reproductive effort and survival provides evidence that survival, to which fitness is most sensitive in long-lived animals, is buffered against temporal variation in brant.

COPD and Cardiovascular Disease

COPD is one of the major public health problems in people aged 40 years or above. It is currently the 4th leading cause of death in the world and projected to be the 3rd leading cause of death by 2020. COPD and cardiac comorbidities are frequently associated. They share common risk factors, pathophysiological processes, signs and symptoms, and act synergistically as negative prognostic factors. Cardiac disease includes a broad spectrum of entities with distinct pathophysiology, treatment and prognosis. From an epidemiological point of view, patients with COPD are particularly vulnerable to cardiac disease. Indeed, mortality due to cardiac disease in patients with moderate COPD is higher than mortality related to respiratory failure. Guidelines reinforce that the control of comorbidities in COPD has a clear benefit over the potential risk associated with the majority of the drugs utilized. On the other hand, the true survival benefits of aggressive treatment of cardiac disease and COPD in patients with both conditions have still not been clarified. Given their relevance in terms of prevalence and prognosis, we will focus in this paper on the management of COPD patients with ischemic coronary disease, heart failure and dysrhythmia.

Identifying optimal candidates for early TIPS among patients with cirrhosis and acute variceal bleeding: a multicentre observational study

ObjectivesEarly placement of transjugular intrahepatic portosystemic shunt (TIPS) has been shown to improve survival in high-risk patients (Child-Pugh B plus active bleeding at endoscopy or Child-Pugh C 10–13) with cirrhosis...

Parameterizing the robust design in the BUGS language: Lifetime carry‐over effects of environmental conditions during growth on a long‐lived bird

Abstract Since the initial development of the robust design, this capture‐recapture model structure has been modified to estimate temporary emigration and expanded to include auxiliary information such as band recovery and live resight data using maximum likelihood approaches. These developments have allowed investigators to separately assess individual and group effects on true survival, site fidelity, and temporary emigration. Additionally, recent advances in the BUGS language have allowed researchers to develop increasingly complex, user‐specified models in Bayesian frameworks. The robust design has rarely been implemented in the BUGS language, and previous attempts to parameterize the robust design in BUGS exhibited strong bias in estimates of temporary emigration rates. Given the limitations of current parameterizations of the robust design in Bayesian frameworks, and our research objectives, we have developed a parameterization of the robust design in the BUGS language that produces unbiased estimates of all model parameters. We use this novel model structure to examine lifetime carry‐over effects of environmental conditions during early life on annual breeding probabilities of Pacific black brent Branta bernicla nigricans breeding on the Yukon–Kuskokwim River Delta in Western Alaska. We found that individuals that were more structurally developed as goslings bred at increased rates as adults (β = 0.14, f = 0.94), with no effect on adult survival (β = 0.01, f = 0.62). Additionally, we provide evidence for long‐term declines in apparent survival of breeding adult females at the population level (β = −0.01, f = 0.90). This novel model structure can be easily expanded (Gibson et al., in press) and has important implications for population modelling at broad scales, where we apply it to a declining population of Pacific black brent. Given long‐term declines in gosling growth on the Yukon–Kuskokwim Delta, we predict future declines in population trajectories as a result of lifetime carry‐over effects of environmental conditions during growth on adult fecundity and long‐term declines in adult survival.

Impacts of anthropogenic disturbance on body condition, survival, and site fidelity of nonbreeding Piping Plovers

ABSTRACT The impact of habitat loss on shorebirds may be exacerbated by disturbance from human recreational use, which further reduces the amount of coastal habitat that is functionally available. This can have consequences for the condition of individual birds or for population processes, both of which should be considered in strategies to reduce conflict between shorebirds and recreational users of coastal habitat. Our objectives were to determine the associations between human recreational use, coastal habitat modifications, and Piping Plover (Charadrius melodus) body condition and demography. We monitored banded Piping Plovers throughout their annual cycle to assess variation in body condition, true survival, and site fidelity related to disturbance regimes in 8 geographically proximate, nonbreeding areas along the southeastern Atlantic Coast of North America from 2012 to 2016. Piping Plovers in disturbed sites were 7% lighter than those in less disturbed sites. Additionally, true annual survival was ...

When is enough … enough? Effective sampling protocols for estimating the survival rates of seabirds with mark-recapture techniques

ABSTRACTCapsule: Lower intensity mark-recapture studies, such as those undertaken by citizen scientists, provide an opportunity to improve the spatial representation of survival estimates for birds. Colonial nesting birds are particularly suited to this because, for many species, large numbers of breeding birds and chicks can be located relatively easily. The minimum level of recapture effort required to accurately estimate true survival rates and detect temporal variation largely depended on the respective ringing effort. Therefore, mark-recapture studies should consider both aspects of the field study when setting or adjusting minimum effort guidelines. Furthermore, achieving reliable estimation with short time-series required more intensive survey designs, highlighting the importance of longevity when planning these studies.Aims: To provide minimum guidelines of field effort that can be used to manage smaller projects that monitor survival rates, such as those reliant on citizen scientists.Methods: We conducted a sensitivity analysis that evaluated the statistical power associated with using different mark-recapture survey designs to estimate a fixed ‘true’ survival rate and detect sources of temporal variation and individual heterogeneity within the population.Results: Isolating temporal variation with a good degree (90%) of certainty required the highest levels of survey effort. Based on the assessed survey designs, we recommend studies that have a ten-year trajectory and a recapture rate of 0.6, aim to mark at least 200 new adults per year. The recommended number of marked individuals will decrease if it is possible to achieve higher rates of recapture. Lower rates of juvenile survival and delayed reproduction mean that seabird mark-recapture survey designs that target both chicks and adults offer only marginal improvements in resolving the survival rates of adults, when compared to designs targeting adults only. However, collecting juvenile mark-recapture data provide access to age-specific vital rates that are also valuable for assessing the population dynamics of seabirds.Conclusion: The addition of chicks is unlikely to improve the resolution of adult survival rates markedly, although for species with low natal dispersal and earlier ages of maturity, these data may allow the estimation of other vital rates, such as juvenile survival rates and age of maturity. Implementing minimum effort guidelines potentially enables the effective management of smaller mark-recapture studies, thus minimising the risk that studies fail to achieve the data conditions necessary for robust estimation of survival rates.

Environmental and ecological conditions at Arctic breeding sites have limited effects on true survival rates of adult shorebirds

ABSTRACT Many Arctic shorebird populations are declining, and quantifying adult survival and the effects of anthropogenic factors is a crucial step toward a better understanding of population dynamics. We used a recently developed, spatially explicit Cormack–Jolly–Seber model in a Bayesian framework to obtain broad-scale estimates of true annual survival rates for 6 species of shorebirds at 9 breeding sites across the North American Arctic in 2010–2014. We tested for effects of environmental and ecological variables, study site, nest fate, and sex on annual survival rates of each species in the spatially explicit framework, which allowed us to distinguish between effects of variables on site fidelity versus true survival. Our spatially explicit analysis produced estimates of true survival rates that were substantially higher than previously published estimates of apparent survival for most species, ranging from S = 0.72 to 0.98 across 5 species. However, survival was lower for the arcticola subspecies of ...

Empirical Comparison of the Breslow Estimator and the Kalbfleisch Prentice Estimator for Survival Functions.

When analyzing time-to-event data in a non-parametric setting without considering covariates, the Kaplan-Meier estimator is widely used to estimate the survival function. When considering covariates, the Cox proportional hazards model is widely used to account for covariates effects. In this setting, for the baseline survival function, the most commonly used approach is the Breslow method, which estimates the baseline survival function as an exponential function of the cumulative baseline hazard function. However, an unnatural and undesirable feature of the Breslow estimator is that, its estimated survival probability will never reaches zero even if the last observation is an event. In this article, we consider an less commonly used alternative, the Kalbfleisch Prentice estimator for the baseline survival function. It is the counterpart of the Kaplan-Meier estimator in a setting with covariates, and thus similarly as the Kaplan Meier estimator, it will reach zero if the last observation is an event. To evaluate the usefulness of the Kalbfleisch Prentice estimator and its relative performance comparing with the Breslow estimator, we conduct simulation studies across a range of conditions by varying the true survival time distribution, sample size, censoring rate and covariate values. We compare the performance of the two estimators regarding bias, mean squared error and relative mean squared error. In most situations in our study, the Kalbfleisch Prentice estimator results in less bias and smaller mean squared error than the Breslow estimator. Their differences are especially clear at the tail of the distribution. The implications of such differences in applications are discussed. We advocate the use of Kalbfleisch Prentice estimator in practice, and further research on its properties.

Treatment of patients with metastatic colorectal cancer and poor performance status: current evidence and challenges

Patients with unresectable metastatic colorectal cancer live for a median of three years when treated with standard therapies. While the evidence guiding cancer-directed treatment of this disease comes from phase III trials that have mostly enrolled patients with good performance status, some patients present with poor clinical conditions. The best treatment for these patients remains to be determined. We performed a systematic review of the treatment outcomes of patients with metastatic colorectal cancer and poor performance status, defined as Eastern Cooperative Oncology Group performance status ≥2. Eligible articles were prospective or retrospective studies or case reports published in English, Portuguese or Spanish. We searched PubMed, EMBASE, LILACS and the Cochrane Library from onset until October 2017 using specific keywords for each search. We found a total of 18 publications, mostly case reports and retrospective studies (14 articles). One was an uncontrolled prospective trial, two were observational studies and one was an individual patient meta-analysis. Although some studies suggested benefits in terms of symptomatic response with standard chemotherapy, with good safety profiles when dose-reduced regimens were administered, a true survival gain could not be demonstrated. The scientific evidence for treating metastatic colorectal cancer patients with poor performance status is scarce, and more studies evaluating treatment for this population are necessary since this condition is not uncommon in clinical practice, particularly in the public healthcare system and developing countries and among destitute populations.

A phase 2 trial of personalized cytotoxic therapy based on tumor immunohistochemistry in previously treated metastatic pancreatic cancer patients.

The choice of a regimen in metastatic pancreatic cancer patients following progression on 1st line therapy is empiric and outcomes are unsatisfactory. This phase II study was performed to evaluate the efficacy of therapy selected by immunohistochemistry (IHC) in these patients following progression after one or more therapies. Eligible patients underwent a percutaneous biopsy of a metastatic lesion and treatment selection was determined by IHC. The study required 35 evaluable patients (power of 86%) for detecting a true 1-year survival rate of >20%. A tumor biopsy was performed in 48 of 49 accrued patients. Study therapy was not given (n=13) either due to insufficient tumor on biopsy (n=8) or due to worsening cancer related symptoms after biopsy (n=5). The demographics of evaluable patients (n=35) are male/female (59%/41%), with age range 34-78 years (median 63 years). Patients had 1-6 prior regimens (median of 2). The most common IHC targets were topoisomerase 1 or 2, thymidylate synthase, excision repair cross-complementation group 1 protein (ERCC1), and osteonectin secreted protein acidic and rich in cysteine (SPARC). Commercially available treatment regimens prescribed included FOLFIRI, FOLFOX, irinotecan, and doxorubicin. The response (RECIST) was 9%, the median survival was 5.6 months (94% CI, 3.8-8.2), and the 1-year survival was 20% (95% CI, 7-33%). In all patients, IHC assays resulted in identification of at least two targets for therapy and a non-cross resistant regimen could be prescribed for therapy with evidence of some benefit. An IHC based treatment strategy is feasible and needs validation in larger studies.

Survival time and prognostic factors of patients with initial noncurative colorectal liver metastases.

The true survival benefit of different curative strategies involving type of operative procedure and timing for patients with initial noncurative colorectal liver metastases remains uncertain. The goal of this study was to examine the effect of primary tumor resection on patients’ survival and to clarify the predictive factors related to overall survival (OS).This was a retrospective study that included 219 patients with initial noncurative colorectal liver metastases without extrahepatic disease. The clinicopathological characteristics of patients and their survival were examined. Survival analysis was performed using the Kaplan–Meier method. All variables associated with P <.05 in univariate analysis were included in multivariate analysis using a Cox proportional-hazard regression model.The 1-, 3-, 5-year OS rates of patients with simultaneous liver resection were 79.1%, 39.1%, and 28.4%, respectively, and those of patients with staged liver resection were 83.3%, 46.7%, and 36.8%, respectively (P = .380). The 1-, 3-, 5-year OS rates of patients with primary tumor resection were 57.0%, 18.2%, and 12.3%, respectively, while for the patients without primary tumor resection were 38.9%, 5.6%, and 0%, respectively (P = .012). Independent prognostic factors for OS were carbohydrate antigen19–9, primary tumor resection, tumor differentiation, and adjuvant chemotherapy.No difference in OS was observed between simultaneous liver resection and staged liver resection, while primary tumor resection was beneficial to noncurative colorectal liver metastases.

Estimation of discrete survival function for error-prone diagnostic tests.

The product limit or Kaplan-Meier (KM) estimator is commonly used to estimate the survival function in the presence of incomplete time to event. Application of this method assumes inherently that the occurrence of an event is known with certainty. However, the clinical diagnosis of an event is often subject to misclassification due to assay error or adjudication error, by which the event is assessed with some uncertainty. In the presence of such errors, the true distribution of the time to first event would not be estimated accurately using the KM method. We develop a method to estimate the true survival distribution by incorporating negative predictive values and positive predictive values, into a KM-like method of estimation. This allows us to quantify the bias in the KM survival estimates due to the presence of misclassified events in the observed data. We present an unbiased estimator of the true survival function and its variance. Asymptotic properties of the proposed estimators are provided, and these properties are examined through simulations. We demonstrate our methods using data from the Viral Resistance to Antiviral Therapy of Hepatitis C study.

Senescence and carryover effects of reproductive performance influence migration, condition, and breeding propensity in a small shorebird.

Breeding propensity, the probability that an animal will attempt to breed each year, is perhaps the least understood demographic process influencing annual fecundity. Breeding propensity is ecologically complex, as associations among a variety of intrinsic and extrinsic factors may interact to affect an animal's breeding decisions. Individuals that opt not to breed can be more difficult to detect than breeders, which can (1) lead to difficulty in estimation of breeding propensity, and (2) bias other demographic parameters. We studied the effects of sex, age, and population reproductive success on the survival and breeding propensity of a migratory shorebird, the piping plover (Charadrius melodus), nesting on the Missouri River. We used a robust design Barker model to estimate true survival and breeding propensity and found survival decreased as birds aged and did so more quickly for males than females. Monthly survival during the breeding season was lower than during migration or the nonbreeding season. Males were less likely to skip breeding (range: 1–17%) than females (range: 3–26%; βsex = −0.21, 95% CI: −0.38 to −0.21), and both sexes were less likely to return to the breeding grounds following a year of high reproductive success. Birds that returned in a year following relatively high population‐wide reproductive output were in poorer condition than following a year with lower reproductive output. Younger adult birds and females were more likely to migrate from the breeding area earlier than older birds and males; however, all birds stayed on the breeding grounds longer when nest survival was low, presumably because of renesting attempts. Piping plovers used a variety of environmental and demographic cues to inform their reproduction, employing strategies that could maximize fitness on average. Our results support the “disposable soma” theory of aging and follow with predictions from life history theory, exhibiting the intimate connections among the core ecological concepts of senescence, carryover effects, and life history.

Prematurity and biliary atresia: a 30-year observational study

Aim of studyThe diagnosis of biliary atresia (BA) remains challenging and delay can lead to significant morbidity with time to surgery a key factor in determining outcome. Prematurity may impact on outcome potentially delaying diagnosis. We sought to assess whether the premature BA infants (PBA) have a delayed time to surgery and as such, worse outcomes?MethodsReview of a single-centre prospectively maintained database. Prematurity was defined as delivery < 37/40 gestation. PBA was compared with date-matched term biliary atresia controls on a 2:1 basis. Primary outcomes were clearance of jaundice (< 20 μmol/L) and native liver survival. A retrospective assessment of liver fibrosis was made on biopsies at diagnosis and at Kasai portoenterostomy (KPE) in both premature and term cohorts. Data are quoted as median (range) unless indicated. A P value of ≤ 0.05 was considered statistically significant.Results21 (female n = 14, 67%) premature infants with BA were treated in the period Jan. 1988–Dec. 2016 and compared with 41 contemporaneous term BA controls. Median gestation was 33 (29–36) weeks and birth weight 1930 (948–4230)g. Twin pregnancy (n = 10) was the leading cause for prematurity and significantly higher than the controls (48 vs. 0%; P < 0.0001). Maternal co-morbidity was high (n = 10, 48%) including pre-eclampsia (19%) and diabetes (14%). Liver biopsy was performed in 19 (90%) patients (all diagnostic) at a median of 57 (4–266) days. Delayed diagnosis (> 50 days) was seen in n = 13 but not associated with parenteral nutrition use (46 vs. 33%, P = 0.59) or phototherapy (50 vs. 83%, P = 0.19). Both BASM (33 vs. 7.5%; P = 0.01) and duodenal atresia (19 vs. 0%; P = 0.01) were seen more frequently in the PBA cohort. Mean fibrosis scores (Ishak) from diagnostic biopsies were lower in the premature group than the control group (2.71 vs. 3.53, P = 0.043) indicating less fibrosis but this equalized by time of subsequent KPE (P = 0.17). Primary surgery was Kasai portoenterostomy (n = 20) at an older median age than controls (65 vs. 56 days; P = 0.06). Liver transplantation was the primary procedure in one late-presenting child. There was an increased but non-significant clearance of jaundice in the PBA group [n = 12/20 (60%) vs 20/41 (48%); P = 0.23] post-KPE. Native liver survival and true survival were not different (P = 0.58 and 0.23).ConclusionsPBA infants have similar outcomes to term infants, despite delayed diagnosis and higher frequency of the syndromic form. The high incidence of discordant twins supports the theory that epigenetic modifications could contribute to the pathogenesis of BA.Level of evidenceIIIc Retrospective Matched Cohort Study.

Nodal stage migration and prognosis in anal cancer: a systematic review, meta-regression, and simulation study

In patients with squamous cell carcinoma of the anus (SCCA), lymph node positivity (LNP) indicates poor prognosis for survival and is central to radiotherapy planning. Over the past three decades, LNP proportion has increased, mainly reflecting enhanced detection with newer imaging modalities; a process known as nodal stage migration. If accompanied by constant T stage distributions, prognosis for both lymph node-positive and lymph node-negative groups may improve without any increase in overall survival for individual patients; a paradox termed the Will Rogers phenomenon. Here, we aim to systematically evaluate the impact of nodal stage migration on survival in SCCA and address a novel hypothesis that this phenomenon results in reduced prognostic discrimination. We did a systematic review and meta-regression to quantify changes in LNP over time and the impact of this change on survival and prognostic discrimination. We searched MEDLINE, Embase, and the Cochrane Library to identify randomised trials and observational studies in patients with SCCA published between Jan 1, 1970, and Oct 11, 2016. Studies were eligible if patients received chemoradiotherapy or radiotherapy as the main treatment, reported LNP proportions (all studies), and reported overall survival (not necessarily present in all studies). We excluded studies with fewer than 50 patients. We extracted study-level data with a standardised, piloted form. The primary outcome measure was 5-year overall survival. To investigate scenarios in which reduced prognostic discrimination might occur, we simulated varying true LNP proportions and true overall survival, and compared these with expected observed outcomes for varying levels of misclassification of true nodal state. We identified 62 studies reporting LNP proportions, which included 10 569 patients. From these, we included 45 studies (6302 patients) with whole cohort 5-year overall survival, 11 studies with 5-year survival stratified by nodal status, and 20 studies with hazard ratios in our analyses of temporal changes. In 62 studies, the LNP proportions increased from a mean estimate of 15·3% (95% CI 10·5-20·1) in 1980 to 37·1% (34·0-41·3) in 2012 (p<0·0001). In 11 studies with prognostic data, increasing LNP was associated with improved overall survival in both lymph node-positive and lymph node-negative categories, whereas the proportions with combined tumour stage T3 and T4 remained constant. In 20 studies, across a range of LNP proportions from 15% to 40%, the hazard ratios for overall survival of lymph node-positive versus lymph node-negative patients decreased significantly from 2·5 (95% CI 1·8-3·3) at 15% LNP to 1·3 (1·2-1·9; p=0·014) at 40% LNP. The simulated scenarios reproduced this effect if the true LNP proportions were 20% or 25%, but not if the true LNP proportions were 30% or greater. We describe a consequence of staging misclassification in anal cancer that we have termed reduced prognostic discrimination. We used this new observation to infer that the LNP proportions of more than 30% seen in modern clinical series (11 out of 15 studies with a median year since 2007) are higher than the true LNP proportion. The introduction of new staging technologies in oncology might misclassify true disease stage, spuriously informing disease management and ultimately increasing the risk of overtreatment. Bowel Disease Research Foundation.