Previous studies examining the incidence of colorectal cancer after polypectomy have provided discordant findings. The aim of this study was to compare the risk of colorectal cancer after adenoma ...removal in routine clinical practice with the risk in the general population.
Cohort study based on detailed data from a population-based registry that has collected all cases of both colorectal cancers and adenomas diagnosed in a clearly-defined population since 1976.
French administrative area of Côte-d'Or (Burgundy).
Residents of the area diagnosed for the first time with colorectal adenoma between 1990 and 1999 were included (n=5779). Initial and follow-up data until December 2003 were used to calculate the colorectal cancer standardised incidence ratio (SIR) and cumulative probabilities after adenoma removal.
After a median follow-up of 7.7 years, 87 invasive colorectal cancers were diagnosed whereas 69 cases were expected. Compared with the general population, the overall SIR was 1.26 (95% CI 1.01 to 1.56). The risk of colorectal cancer depended on the characteristics of the initial adenoma (SIR 2.23 (95% CI 1.67 to 2.92) for advanced adenomas and 0.68 (95% CI 0.44 to 0.99) for non-advanced adenomas). In cases of advanced adenomas, the SIR was 1.10 (95% CI 0.62 to 1.82) in patients with colonoscopic follow-up and 4.26 (95% CI 2.89 to 6.04) in those without. The 10-year cumulative probabilities of colorectal cancer were, respectively, 2.05% (95% CI 1.14% to 3.64%) and 6.22% (95% CI 4.26% to 9.02%).
In routine practice, the risk of colorectal cancer after adenoma removal remains high and depends both on initial adenoma features and on colonoscopy surveillance practices. Gastroenterologists should encourage patients to comply with long-term colonoscopic surveillance.
Background
Cancer prevalence is heterogeneous because it includes individuals who are undergoing initial treatment and those who are in remission, experiencing relapse, or cured. The proposed ...statistical approach describes the health status of this group by estimating the probabilities of death among prevalent cases. The application concerns colorectal, lung, breast, and prostate cancers and melanoma in France in 2017.
Methods
Excess mortality was used to estimate the probabilities of death from cancer and other causes.
Results
For the studied cancers, most deaths from cancer occurred during the first 5 years after diagnosis. The probability of death from cancer decreased with increasing time since diagnosis except for breast cancer, for which it remained relatively stable. The time beyond which the probability of death from cancer became lower than that from other causes depended on age and cancer site: for colorectal cancer, it was 6 years after diagnosis for women (7 years for men) aged 75–84 and 20 years for women (18 years for men) aged 45–54 years, whereas cancer was the major cause of death for women younger than 75 years whatever the time since diagnosis for breast and for all patients younger than 75 years for lung cancer. In contrast, deaths from other causes were more frequent in all the patients older than 75 years. Apart from breast cancer in women younger than 55 years and lung cancer in women older than 55 years and men older than 65 years, the probability of death from cancer among prevalent cases fell below 1%, with varying times since diagnosis.
Conclusions
The authors' approach can be used to better describe the burden of cancer by estimating outcomes in prevalent cases.
Cancer prevalence covers a population whose health status is heterogeneous. A statistical approach that combined prevalence and crude probabilities of death was used to demonstrate that the distribution of prevalent cases regarding the risk of death according to causes varied by cancer site, time since diagnosis, and age.
The CpG island methylator phenotype (CIMP) is a distinct phenotype in colorectal cancer, associated with specific clinical, pathologic, and molecular features. However, most of the studies stratified ...methylation according to two subgroups (CIMP-High versus No-CIMP/CIMP-Low). In our study, we defined three different subgroups of methylation (No-CIMP, CIMP-Low, and CIMP-High) and evaluated the prognostic significance of methylation status on a population-based series of sporadic colon cancers. A total of 582 colon adenocarcinomas were evaluated using methylation-specific PCR for 5 markers (hMLH1, P16, MINT1, MINT2, and MINT31). No-CIMP status was defined as no methylated locus, CIMP-Low status as one to three methylated loci, and CIMP-High status as four or five methylated loci. Clinicopathologic and molecular characteristics were correlated to the methylation status. Crude and relative survival was compared according to methylation status. In the microsatellite-stable (MSS) group, CIMP-High was significantly associated with proximal location (P = 0.011) and BRAF mutation (P < 0.001). KRAS mutations were more associated with CIMP-High and CIMP-Low status (P = 0.008). A shorter 5-year survival was observed in MSS cancer patients with CIMP-Low or CIMP-High status. These results remained significant in multivariate analysis adjusted for age, stage, and BRAF and KRAS mutational status CIMP-Low: hazard ratio (HR), 1.85; 95% confidence interval (95% CI), 1.37-2.51; CIMP-High, HR, 2.90; 95% CI, 1.53-5.49 compared with No-CIMP. Within the high-level microsatellite instability group, no difference in survival was observed between the different CIMP groups. Our results show the interest of defining three subgroups of patients according to their methylation status (No-CIMP/CIMP-Low/CIMP-High). Methylation is an independent prognostic factor in MSS colon cancer.
Pancreatic survival is one of the worst in oncology. To what extent wait times affect outcomes in unknown No population‐based study has previously explored patient and treatment delays among ...individuals with pancreatic cancer. The aim of this study was to estimate patient and treatment delays in patients with pancreatic cancer and to measure their association with survival in a nonselected population. All patients diagnosed with pancreatic cancer for the first time between 2009 and 2011 and registered in two French digestive cancer registries were included. Patient delay (time from onset of symptoms until the first consultation categorized into <1 or ≥1 month), and treatment delay (time between the first consultation and treatment categorized into less or more than 29 days, the median time) were collected. Overall delay was used to test associations between survival and the timeliness of care by combining patient delay and treatment delay. Patient delay was longer than 1 month in 46% of patients. A patient delay longer than one month was associated with the absence of jaundice (p < 0.001) and the presence of metastasis (p = 0.003). After adjusting for other covariates, such as symptoms and treatment, the presence of metastasis was negatively associated with treatment delay longer than 29 days (p = 0.025). After adjustment for other covariates, especially metastatic dissemination and the result of the resection, overall delay was not significantly associated with prognosis. We found little evidence to suggest that timely care was associated with the survival of patients.
What's new?
Survival rates for pancreatic cancer remain exceedingly low. But while the disease often is not detected until advanced stages, whether delays in seeking physician care and in receiving treatment contribute to poor survival is unclear. In this population‐based study in France, the presence of jaundice and metastatic dissemination were the two most relevant factors related to the timeliness of care, causing patients to consult a physician and being associated with short treatment delays. Nonetheless, timeliness of care had no impact on survival. The findings suggest that the advance of novel therapeutics will be key to improving pancreatic cancer survival.
Epidemiological data on synchronous and metachronous lung metastases from colorectal cancer are scarce. The aim of this study was to determine trends in the incidence, treatment and survival in ...colorectal cancer with lung metastases in the general population.
All cases of lung metastases from colorectal cancer registered in the Burgundy digestive cancer registry between 1976 and 2005 were included. Trends in the incidence of synchronous colorectal cancer lung metastases were estimated. A Cox model was used to analyse the risk of developing a metachronous metastasis. Multivariate analyses were performed using a relative survival model with proportional hazard applied to the net survival by interval.
Overall, 11.0% of patients had synchronous lung metastases. The frequency of synchronous lung metastases significantly increased for both sexes over time, with a nearly threefold increase between the periods 1976-1985 and 1996-2005. The overall 5-year cumulative risk of developing metachronous lung metastases was 5.8%. It did not significantly vary with time. Compared to colon cancer, rectal cancers had a higher risk of developing synchronous (OR: 2.80 (1.65-4.76)) and metachronous (OR: 2.63 (1.69-4.08)) lung metastases. Overall, 4.1% of synchronous lung metastases and 14.3% of metachronous lung metastases were resected for cure. The 3-year relative survival was 11.3% for synchronous lung metastases and 13.8% for metachronous lung metastases. It was, respectively, 53.0% and 59.2% after resection for cure. In multivariate analysis, the relative risk of death for the 1996-2005 period was about one fifth of that for the 1976-1985 period.
The incidence of synchronous lung metastases increased over time, whereas the incidence of metachronous lung metastases remained stable. Lung metastases were more frequent in rectal cancer than in colon cancer. Unless surgical resection is possible, the prognosis for lung metastases remains very poor.
As cancer treatment, biotherapies can be as effective as chemotherapy while reducing the risk of secondary effects, so that they can be taken over longer periods than conventional chemotherapy. Thus, ...some trials aimed at assessing the benefit of maintaining biotherapies during chemotherapy-free intervals (CFI). For example, the recent PRODIGE9 trial assessed the effect of maintaining bevacizumab during CFI in metastatic colorectal cancer (mCRC) patients. However, its analysis was hindered by a small difference of exposure to the treatment between the randomized groups and by a large proportion of early drop outs, leading to a potentially unbalanced distribution of confounding factors among the trial completers. To address these limitations, we re-analyzed the PRODIGE9 data to assess the effects of different exposure metrics on all-cause mortality of patients with mCRC using methods originally developed for observational studies.
To account for the actual patterns of drug use by individual patients and for possible cumulative effects, we used five alternative time-varying exposure metrics: (i) cumulative dose, (ii) quantiles of the cumulative dose, (iii) standardized cumulative dose, (iv) Theoretical Blood Concentration (TBC), and (v) Weighted Cumulative Exposure (WCE). The last two metrics account for the timing of drug use. Treatment effects were estimated using adjusted Hazard Ratio from multivariable Cox proportional hazards models.
After excluding 112 patients who died during the induction period, we analyzed data on 382 patients, among whom 320 (83.8%) died. All time-varying exposures improved substantially the model's fit to data, relative to using only the time-invariant randomization group. All exposures indicated a protective effect for higher cumulative bevacizumab doses. The best-fitting WCE and TBC models accounted for both the cumulative effects and the different impact of doses taken at different times.
All time-varying analyses, regardless of the exposure metric used, consistently suggested protective effects of higher cumulative bevacizumab doses. However, the results may partly reflect the presence of a confusion bias. Complementing the main ITT analysis of maintenance trials with an analysis of potential cumulative effects of treatment actually taken can provide new insights, but the results must be interpreted with caution because they do not benefit from the randomization.
clinicaltrials.gov, NCT00952029 . Registered 8 August 2009.
Population-based studies on colorectal malignant polyps (MPs) are scarce. The aim of this study was to describe time trends in the incidence of colorectal MPs before and after the introduction of a ...colorectal mass-screening programmein 2003 and to assess outcomes (survival and recurrence) after endoscopic or surgical resection in patients with MPs.
We included 411 patients with MPs diagnosed between 1982 and 2011 in a well-defined population. Age-standardised incidence rates were calculated. Univariate and multivariate 5-year recurrence and net survival analyses were performed according to gross morphology.
Age-standardised incidence of MPs in patients aged 50-74 years doubled from 5.4 in 1982-2002 to 10.9 per 100 000 in 2003-2011. Pedunculated MPs were more frequently resected endoscopically (38.2%) than were sessile MPs (19.1%;
<0.001). For patients with pedunculated MPs and a pathological margin ≥1 mm, the 5 -year cumulative recurrence rate did not differ significantly between surgical and endoscopic resection (8.2% and 2.4%, respectively). For patients with sessile MPs, it was 3.0% after first-line or second-line surgical resection, 8.6% after endoscopic resection and 17.9% after transanal resection (p=0.016). The recurrence rate decreased dramatically for patients with sessile MPs from 11.3% (1982-2002) to 1.2% (2003-2009) (p=0.010) and remained stable for pedunculated MPs at 4.6% and 6.7%, respectively. Five-year net survival was 81.0% when pathological margins were <1 mm and 95.6% when ≥1 mm (p=0.024).
Outcomes following polypectomy in patients with a pathological margin ≥1 mm are similar to those following surgery in the general population. Endoscopic resection needs to be completed by surgery if pathological margins are less than 1 mm.
Background and Aims
Data concerning the risk of long‐term liver metastasis following surgery of colorectal cancer in the general population are scarce. The 10‐year incidence and prognosis of ...metachronous liver metastases remain unknown.
Methods
Among 4584 patients resected for cure for colorectal cancer recorded in two French digestive population‐based cancer registries between 1985 and 2000, 602 presented metastases including liver metastases.
Results
The cumulated incidence of liver metastasis was 15% at 5 years and 17% at 10 years, and was mainly related to stage at diagnosis. The 10‐year cumulative incidence was 6% for stage I and 30% for stage III. The hazard ratio was 3.2 2.4–4.3 for stage II and 6.9 5.1–9.2 for stage III compared with stage I. Among survivors with no recurrence five years after diagnosis, 2.2% developed liver metastasis between 5 and 10 years. Resection for cure of liver metastases was performed in 35% of patients aged under 75 years and in 10% of patients over 75 (P < 0.001). After resection for cure, 10‐year relative survival improved from 21% during the period 1985–1997 to 34% during the period 1998–2011 (P = 0.023). Survival in patients with liver metastasis diagnosed between six and 12 months after surgery was less than half that in patients with metastasis diagnosed later (HR: 0.6 0.4–1.0).
Conclusion
Liver metastases from colorectal cancer remain a substantial problem and continue to occur long after five years. This study furnishes unbiased figures that can be used as a reference. Liver metastases that appear late have a better prognosis.
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•Time to “statistical” cure is a key indicator in cancer survival studies.•It can provide estimations of the time to access insurance or bank loans without overtaxes for people ...diagnosed with cancer.•We propose a new definition of the time-to-cure based on the estimated covariate-specific probability of being cured.•According to cancer site, time-to-cure varies from 0 to 10 years after diagnosis.
Cure models have been adapted to net survival context to provide important indicators from population-based cancer data, such as the cure fraction and the time-to-cure. However existing methods for computing time-to-cure suffer from some limitations.
Cure models in net survival framework were briefly overviewed and a new definition of time-to-cure was introduced as the time TTC at which P(t), the estimated covariate-specific probability of being cured at a given time t after diagnosis, reaches 0.95. We applied flexible parametric cure models to data of four cancer sites provided by the French network of cancer registries (FRANCIM). Then estimates of the time-to-cure by TTC and by two existing methods were derived and compared. Cure fractions and probabilities P(t) were also computed.
Depending on the age group, TTC ranged from to 8 to 10 years for colorectal and pancreatic cancer and was nearly 12 years for breast cancer. In thyroid cancer patients under 55 years at diagnosis, TTC was strikingly 0: the probability of being cured was >0.95 just after diagnosis. This is an interesting result regarding the health insurance premiums of these patients. The estimated values of time-to-cure from the three approaches were close for colorectal cancer only.
We propose a new approach, based on estimated covariate-specific probability of being cured, to estimate time-to-cure. Compared to two existing methods, the new approach seems to be more intuitive and natural and less sensitive to the survival time distribution.
Long‐term recurrences of colon cancer raised questions about the possible benefit of prolonging the recommended active 5‐year surveillance. The aim of this study was to determine, for the first time, ...the incidence and patterns of late 10‐year recurrence following curative resection of colon cancer. Data were obtained from two French digestive cancer registries. A total of 3,622 patients under 85 years resected for cure for colon cancer diagnosed between 1985 and 2000 were included. Information regarding recurrences was actively collected. Cumulative failure rates at 10 years were estimated using Kaplan–Meier estimates corrected by cause‐specific hazards, and multivariable analysis was performed using a model for the subdistribution of a competing risk proposed by Fine and Gray. The overall cumulative recurrence rate between 5 and 10 years after initial surgery was 2.9% for local recurrence and 4.3% for distant metastasis. Among men with no recurrence 5 years after diagnosis of colon cancer, 1 in 12 developed a recurrence between 5 and 10 years, and the corresponding cumulative rate was 7.8%. The frequency was 1 in 19 for women, corresponding to a cumulative rate of 5.2%. In the multivariate analysis, non‐emergency diagnostic feature, female sex and age under 75 were associated with a lower risk of recurrence. Stage at diagnosis was not a predictor of late recurrence. Late recurrence after colon cancer resection with curative intent can occur. A regular clinical follow‐up is necessary to detect early signs of possible recurrence.
What's new?
The recurrence of colon cancer more than 5 years following surgery for curative resection is a significant concern for patients. Yet, little is known about the epidemiology of late recurrence for colon cancer. Here, among more than 3,600 patients who underwent resection with intention to cure, 1 man in every 12 and 1 woman in every 19 was affected by late recurrence, defined as the return of colon cancer between 5 and 10 years after surgery. The findings suggest that regular follow‐up beyond 5 years may be needed in order to catch recurrence in a timely manner.
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