Evaluating cancer screening programs using survival analysis

The main purpose of cancer screening programs is to provide early treatment to patients that are diagnosed with cancer on a screening test, thus increasing their chances of survival. To test this hypothesis directly, one should compare the survival of screen-detected cases to the survival of their counterparts not included to the program. In this study, we develop a general notation and use it to formally define the comparison of interest. We explain why the naive comparison between screen-detected and interval cases is biased and show that the total bias that arises in this case can be decomposed as a sum of lead time bias, length time bias, and bias due to overdetection. With respect to the estimation, we show what can be estimated using existing methods. To fill in the missing gap, we develop a new nonparametric estimator that allows us to estimate the survival of the control group, that is, the survival of cancer cases that would be screen-detected among those not included to the program. By joining the proposed estimator with existing methods, we show that the contrast of interest can be estimated without neglecting any of the biases. Our approach is illustrated using simulations and empirical data.     

Risk of prostate cancer among cancer survivors in the Netherlands

BackgroundIn parallel with increasing numbers of cancer patients and improving cancer survival, the occurrence of second primary cancers becomes a relevant issue. The aim of our study was to evaluate risk of prostate cancer as second primary cancer in a population-based setting.MethodsData from the Netherlands Cancer Registry were used to estimate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for prostate cancer as second primary cancer. The effect of time since first cancer diagnosis, specific first cancer sites, age, and pelvic radiotherapy was taken into account.ResultsOut of 551,553 male patients diagnosed with a first primary cancer between 1989 and 2008, 9243 patients were subsequently diagnosed with prostate cancer. Overall, cancer survivors showed an increased risk (SIR 1.3, 95% CI 1.2–1.3) of prostate cancer. The increased prostate cancer risk was limited to the first year of follow-up for the majority of the specific first cancer sites. More than 10 years after the first cancer diagnosis, only melanoma patients were at increased risk (SIR 1.5, 95% CI 1.2–1.9), while patients with head or neck cancers were at decreased risk (SIR 0.7, 95% CI 0.5–0.9) of being diagnosed with prostate cancer. Patients who underwent primary pelvic radiotherapy for their first cancer had a decreased risk of prostate cancer in the long term (SIR 0.5, 95% CI 0.4–0.6).ConclusionsOur data showed that cancer survivors have an increased prostate cancer risk in the first year following a first cancer diagnosis, which is most likely the result of active screening or incidental detection.     

Randomization to Screening for Prostate,Lung, Colorectal and Ovarian Cancers and Thyroid Cancer Incidence in Two Large Cancer Screening Trials

Background

Thyroid cancer incidence has increased significantly over the past three decades due, in part, to incidental detection. We examined the association between randomization to screening for lung, prostate, colorectal and/or ovarian cancers and thyroid cancer incidence in two large prospective randomized screening trials.

Methods

We assessed the association between randomization to low-dose helical CT scan versus chest x-ray for lung cancer screening and risk of thyroid cancer in the National Lung Screening Trial (NLST). In the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO), we assessed the association between randomization to regular screening for said cancers versus usual medical care and thyroid cancer risk. Over a median 6 and 11 years of follow-up in NLST and PLCO, respectively, we identified 60 incident and 234 incident thyroid cancer cases. Cox proportional hazards regression was used to calculate the cause specific hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer.

Results

In NLST, randomization to lung CT scan was associated with a non-significant increase in thyroid cancer risk (HR  = 1.61; 95% CI: 0.96–2.71). This association was stronger during the first 3 years of follow-up, during which participants were actively screened (HR  = 2.19; 95% CI: 1.07–4.47), but not subsequently (HR  = 1.08; 95% CI: 0.49–2.37). In PLCO, randomization to cancer screening compared with usual care was associated with a significant decrease in thyroid cancer risk for men (HR  = 0.61; 95% CI: 0.49–0.95) but not women (HR  = 0.91; 95% CI: 0.66–1.26). Similar results were observed when restricting to papillary thyroid cancer in both NLST and PLCO.

Conclusion

Our study suggests that certain medical encounters, such as those using low-dose helical CT scan for lung cancer screening, may increase the detection of incidental thyroid cancer.     

Prostate cancer specific survival in the Prostate,Lung, Colorectal,and Ovarian (PLCO) Cancer Screening Trial

Background: The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized screening trial demonstrated no mortality effect of screening. Here we analyze prostate cancer specific survival in PLCO and its relation to screening. Methods: 76,693 men aged 55–74 were randomized to usual care (n = 38,350) or intervention (n = 38,343). Intervention arm men received annual prostate-specific antigen (6 years) and digital rectal exam (4 years). Men were followed for cancer diagnosis and mortality through 13 years. Medical record abstractors confirmed prostate cancer diagnoses, stage and grade. Prostate-specific survival in PLCO cases was analyzed using Kaplan–Meier analysis and proportional hazards modeling. We utilized data from the Surveillance, Epidemiology and End Results (SEER) program to compute expected survival in PLCO and compared this to observed. Results: There was no significant difference in prostate-specific survival rates between arms; 10 year survival rates were 94.7% (intervention, n = 4250 cases) versus 93.5% (usual care, n = 3815 cases). Within the intervention arm, cases never screened in PLCO had lower 10 year survival rates (82%) than screen detected or interval (following a negative screen) cases, both around 95.5%. The ratio of observed to expected 10 year prostate-specific death (1-survival) rates was 0.59 (95% CI: 0.51–0.68) for all PLCO cases, 0.66 (95% CI: 0.51–0.81) for Gleason 5–7 cases and 1.07 (95% CI: 0.87–1.3) for Gleason 8–10 cases. Conclusion: Prostate cancer specific survival in PLCO was comparable across arms and significantly better than expected based on nationwide population data. How much of the better survival is due to a healthy volunteer effect and to lead-time and overdiagnosis biases is not readily determinable.     

Survival Analysis of Patients with Interval Cancer Undergoing Gastric Cancer Screening by Endoscopy

AimsInterval cancer is a key factor that influences the effectiveness of a cancer screening program. To evaluate the impact of interval cancer on the effectiveness of endoscopic screening, the survival rates of patients with interval cancer were analyzed.MethodsWe performed gastric cancer-specific and all-causes survival analyses of patients with screen-detected cancer and patients with interval cancer in the endoscopic screening group and radiographic screening group using the Kaplan-Meier method. Since the screening interval was 1 year, interval cancer was defined as gastric cancer detected within 1 year after a negative result. A Cox proportional hazards model was used to investigate the risk factors associated with gastric cancer-specific and all-causes death.ResultsA total of 1,493 gastric cancer patients (endoscopic screening group: n = 347; radiographic screening group: n = 166; outpatient group: n = 980) were identified from the Tottori Cancer Registry from 2001 to 2008. The gastric cancer-specific survival rates were higher in the endoscopic screening group than in the radiographic screening group and the outpatients group. In the endoscopic screening group, the gastric cancer-specific survival rate of the patients with screen-detected cancer and the patients with interval cancer were nearly equal (P = 0.869). In the radiographic screening group, the gastric cancer-specific survival rate of the patients with screen-detected cancer was higher than that of the patients with interval cancer (P = 0.009). For gastric cancer-specific death, the hazard ratio of interval cancer in the endoscopic screening group was 0.216 for gastric cancer death (95%CI: 0.054-0.868) compared with the outpatient group.ConclusionThe survival rate and the risk of gastric cancer death among the patients with screen-detected cancer and patients with interval cancer were not significantly different in the annual endoscopic screening. These results suggest the potential of endoscopic screening in reducing mortality from gastric cancer.     

Estimating bias in causes of death ascertainment in the Finnish Randomized Study of Screening for Prostate Cancer

BackgroundPrecise cause of death (CoD) ascertainment is crucial in any cancer screening trial to avoid bias from misclassification due to excessive recording of diagnosed cancer as a CoD in death certificates instead of non-cancer disease that actually caused death. We estimated whether there was bias in CoD determination between screening (SA) and control arms (CA) in a population-based prostate cancer (PCa) screening trial.MethodsOur trial is the largest component of the European Randomized Study of Screening for Prostate Cancer with more than 80,000 men. Randomly selected deaths in men with PCa (N = 442/2568 cases, 17.2%) were reviewed by an independent CoD committee. Median follow-up was 16.8 years in both arms.ResultsOverdiagnosis of PCa was present in the SA as the risk ratio for PCa incidence was 1.19 (95% confidence interval (CI) 1.14–1.24). The hazard ratio (HR) for PCa mortality was 0.94 (95%CI 0.82–1.08) in favor of the SA. Agreement with official CoD registry was 94.6% (κ = 0.88) in the SA and 95.4% (κ = 0.91) in the CA. Altogether 14 PCa deaths were estimated as false-positive in both arms and exclusion of these resulted in HR 0.92 (95% CI 0.80–1.06).ConclusionsA small differential misclassification bias in ascertainment of CoD was present, most likely due to attribution bias (overdiagnosis in the SA). Maximum precision in CoD ascertainment can only be achieved with independent review of all deaths in the diseased population. However, this is cumbersome and expensive and may provide little benefit compared to random sampling.     

Associations between an obesity related genetic variant (FTO rs9939609) and prostate cancer risk

Observational studies suggest that obese men have a lower risk of incident prostate cancer, but an increased risk of advanced and fatal cancers. These observations could be due to confounding, detection bias, or a biological effect of obesity. Genetic studies are less susceptible to confounding than observational epidemiology and can suggest how associations between phenotypes (such as obesity) and diseases arise. To determine whether the associations between obesity and prostate cancer are causal, we conducted a genetic association study of the relationship between a single nucleotide polymorphism known to be associated with obesity (FTO rs9939609) and prostate cancer. Data are from a population-based sample of 1550 screen-detected prostate cancers, 1815 age- and general practice matched controls with unrestricted prostate specific antigen (PSA) values and 1175 low-PSA controls (PSA <0.5 ng/ml). The rs9939609 A allele, which was associated with higher BMI in the sample, was inversely associated with overall (odds ratio (OR) versus all controls = 0.93; 95% confidence interval (CI): 0.85-1.02 p = 0.12 per allele) and low-grade (OR = 0.90; 0.81-0.99 p = 0.03 per allele) prostate cancer risk, but positively associated with high-grade cancer among cases (OR high- versus low-grade cancer = 1.16; 0.99-1.37 p = 0.07 per allele). Although evidence for these effects was weak, they are consistent with observational data based on BMI phenotypes and suggest that the observed association between obesity and prostate cancer is not due to confounding. Further research should confirm these findings, extend them to other BMI-related genetic variants and determine whether they are due to detection bias or obesity-related hormonal changes. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN20141297.     

Changes in prostate cancer incidence,mortality and survival in relation to prostate specific antigen testing in New South Wales,Australia

BackgroundTo examine changes in prostate cancer incidence and mortality rates, and 5-year relative survival, in relation to changes in the rate of prostate specific antigen (PSA) screening tests and the use of radical prostatectomy (RP) in the Australian population.MethodsProstate cancer stage-specific incidence rates, 5-year relative survival and mortality rates were estimated using New South Wales Cancer Registry data. PSA screening test rates and RP/Incidence ratios were estimated from Medicare Benefits Schedule claims data. We used multiple imputation to impute stage for cases with “unknown” stage at diagnosis. Annual percentage changes (APC) in rates were estimated using Joinpoint regression.ResultsTrends in the age-standardized incidence rates for localized disease largely mirrored the trends in PSA screening test rates, with a substantial ‘spike’ in the rates occurring in 1994, followed by a second ‘spike’ in 2008, and then a significant decrease from 2008 to 2015 (APC −6.7, 95% CI −8.2, −5.1). Increasing trends in incidence rates were observed for regional stage from the early 2000s, while decreasing or stable trends were observed for distant stage since 1993. The overall RP/Incidence ratio increased from 1998 to 2003 (APC 9.6, 95% CI 3.8, 15.6), then remained relatively stable to 2015. The overall 5-year relative survival for prostate cancer increased from 58.4% (95% CI: 55.0–61.7%) in 1981–1985 to 91.3% (95% CI: 90.5–92.1%) in 2011–2015. Prostate cancer mortality rates decreased from 1990 onwards (1990–2006: APC −1.7, 95% CI −2.1, −1.2; 2006–2017: APC −3.8, 95% CI −4.4, −3.1).ConclusionsOverall, there was a decrease in the incidence rate of localized prostate cancer after 2008, an increase in survival over time and a decrease in the mortality rate since the 1990s. This seems to indicate that the more conservative use of PSA screening tests in clinical practice since 2008 has not had a negative impact on population-wide prostate cancer outcomes.     

Diagnostic Intervals and Its Association with Breast,Prostate, Lung and Colorectal Cancer Survival in England: Historical Cohort Study Using the Clinical Practice Research Datalink

Rapid diagnostic pathways for cancer have been implemented, but evidence whether shorter diagnostic intervals (time from primary care presentation to diagnosis) improves survival is lacking. Using the Clinical Practice Research Datalink, we identified patients diagnosed with female breast (8,639), colorectal (5,912), lung (5,737) and prostate (1,763) cancers between 1998 and 2009, and aged >15 years. Presenting symptoms were classified as alert or non-alert, according to National Institute for Health and Care Excellence guidance. We used relative survival and excess risk modeling to determine associations between diagnostic intervals and five-year survival. The survival of patients with colorectal, lung and prostate cancer was greater in those with alert, compared with non-alert, symptoms, but findings were opposite for breast cancer. Longer diagnostic intervals were associated with lower mortality for colorectal and lung cancer patients with non-alert symptoms, (colorectal cancer: Excess Hazards Ratio, EHR >6 months vs <1 month: 0.85; 95% CI: 0.72-1.00; Lung cancer: EHR 3-6 months vs <1 month: 0.87; 95% CI: 0.80-0.95; EHR >6 months vs <1 month: 0.81; 95% CI: 0.74-0.89). Prostate cancer mortality was lower in patients with longer diagnostic intervals, regardless of type of presenting symptom. The association between diagnostic intervals and cancer survival is complex, and should take into account cancer site, tumour biology and clinical practice. Nevertheless, unnecessary delay causes patient anxiety and general practitioners should continue to refer patients with alert symptoms via the cancer pathways, and actively follow-up patients with non-alert symptoms in the community.     

Survival disparities for childhood cancers exist when defined by race/ethnicity and sex

BackgroundThere are documented racial/ethnic and sex differences in pediatric cancer survival; however, it is unknown whether pediatric cancer survival disparities exist when race/ethnicity and sex are considered jointly.MethodsUsing SEER data (2000–2017), we estimated survival differences by race/ethnicity within sexes and by sex within race/ethnicity (White, Black, Hispanic, and Asian/Pacific Islander [API]) for 17 cancers in children aged (0–19 years). Kaplan-Meier curves (Log-Rank p-values) were assessed. Cox regression was used to estimate hazards ratios (HRs) and 95 % confidence intervals (95 % CIs) between race/ethnicity/sex and cancer.ResultsWe included 51,759 cases (53.6 % male, 51.9 % White). There were statistically significant differences in 18-year survival by race/ethnicity-sex for 12/17 cancers. Within sexes, minorities had an increased risk of death compared to Whites for various cancers including acute lymphoblastic leukemia (ALL) (females: HispanicHR: 1.78, 95 % CI: 1.52, 2.10; BlackHR: 1.70, 95 % CI: 1.29, 2.24; APIHR: 1.42, 95 % CI: 1.07–1.89; males ALL: HispanicHR: 1.58, 95 % CI: 1.39,1.79; BlackHR: 1.57, 95 % CI: 1.26,1,95; API-HR: 1.39, 95 % CI: 1.11, 1.75) and astrocytoma (females: HispanicHR: 1.49, 95 % CI: 1.19, 1.85; BlackHR: 1.67, 95 % CI: 1.29, 2.17; API-HR: 1.51, 95 % CI: 1.05, 2.15; males: HispanicHR:1.27, 95 % CI: 1.04, 1.56; BlackHR: 1.69, 95 % CI: 1.32, 2.17; API-HR: 1.92, 95 % CI: 1.43, 2.58). Sex differences in survival within racial/ethnic groups were observed for White (ALL, osteosarcoma), Hispanic (medulloblastoma), and API (Primitive Neuro-Ectodermal Tumor [PNET]) children.ConclusionsThere are disparities in survival by both race/ethnicity and sex highlighting the societal and biologic influences these features have on survival in children with cancer.     

Evaluation of a colorectal cancer screening program composed of successive waves of different tests: The experience of the French Calvados County

BackgroundsThe value of colorectal cancer (CRC) screening program in a population with a limited participation rate is debated. This study assesses the real-life performances of different screening tests in a population benefiting from an organized program and included in a cancer registry.MethodsPatients who participated in at least one screening campaign between 2004 and 2016 were included. Four screening procedures were used: Hemoccult II, Magstream, Hemoccult and Magstream combined, and OC Sensor. Data were crossed with the Digestive Cancer Registry of Calvados to detect CRCs diagnosed during this period. The main outcomes were CRC detection and the incidence rate of interval cancers.ResultsScreening consisted of 325,083 tests in 134,498 patients. Of the 2580 CRCs detected in patients aged 50–74, 534 (20.7 %) were screen-detected. OC Sensor had the highest sensitivity for CRC detection (83.7 %, 95 % CI [76.8–89.1 %]) and the lowest interval cancer rate (2.0 per 10,000 person-years, 95 % CI [1.4–2.7]) compared with other screening tests, excluding combinations. The overall participation rate was 28.9 %.ConclusionReal-life differences in performance between different screening tests exist, and OC Sensor appears to be the best. The low participation rate suggests that the rate of screen-detected CRC could be higher.     

Bias in survival estimates created by a requirement for consent to enter a clinical breast cancer registry

BackgroundA requirement for consent for inclusion may bias the results from a clinical registry. This study gives a direct measure of this bias, based on a population-based clinical breast cancer registry where the requirement for consent was removed after further ethical review and data could be re-analysed.MethodsIn Auckland, New Zealand, the population-based clinical breast cancer registry required written patient consent for inclusion from 2000-2012. A subsequent ethical review removed this requirement and allowed an analysis of consented and non-consented patients. Kaplan-Meier survival to 10 years (mean follow-up 5.1 years, maximum 13.9 years), demographic and clinical characteristics were compared. Of 9244 women with invasive cancer, 926 (10.4%) were not consented, and of 1642 women with ductal carcinoma in situ, 245 (14.9%) were not consented.ResultsSurvival was much higher for consenting patients; invasive cancer, 5 year survival 83.2% (95% confidence limits 82.2–84.1%) for consenting patients, 57.1% (53.0–60.9%) for non-consenting, and 80.8% in all patients. Analyses based only on consenting patients overestimate survival in all patients by around 2% at 2, 5, and 10 years. Non-consented patients were older, more often of Pacific ethnicity, had fewer screen-detected cancers, and more often had metastatic disease; they less frequently had primary surgery or systemic treatments.ConclusionData from a registry requiring active consent gives an upward bias in survival results, as non-consenting patients have more extensive disease, less treatment, and lower survival. To give unbiased results active consent should be not required in a clinical cancer registry.     

Lack of Association of the N-acetyltransferase NAT1*10 Allele with Prostate Cancer Incidence, Grade, or Stage Among Smokers in Finland

Genetic variations in xenobiotic metabolizing genes can influence susceptibility to many environmentally induced cancers. Inheritance of the N-acetyltransferase 1 allele (NAT1*10), linked with increased metabolic activation of pro-carcinogens, is associated with an increased susceptibility to many cancers in which cigarette- or meat-derived carcinogens have been implicated in their etiology. The role of NAT1*10 in prostate cancer is under studied. Although cigarette smoking is not considered a risk factor for prostate cancer, a recent review suggests it may play a role in disease progression. Consequently, we examined the association of NAT1*10 with prostate cancer risk, grade, and stage among 400 Finnish male smokers using a case-control study design. Following genotyping of 206 patients and 196 healthy controls, our results do not support the role of NAT1*10 in relation to prostate cancer risk (OR?=?1.28; 95% CI, 0.66-2.47), aggressive disease (OR?=?0.58; 95% CI, 0.13-2.67), or advanced disease (OR?=?1.19; 95% CI, 0.49-2.91).     

Impact of Risk Factors on Different Interval Cancer Subtypes in a Population-Based Breast Cancer Screening Programme

Background

Interval cancers are primary breast cancers diagnosed in women after a negative screening test and before the next screening invitation. Our aim was to evaluate risk factors for interval cancer and their subtypes and to compare the risk factors identified with those associated with incident screen-detected cancers.

Methods

We analyzed data from 645,764 women participating in the Spanish breast cancer screening program from 2000–2006 and followed-up until 2009. A total of 5,309 screen-detected and 1,653 interval cancers were diagnosed. Among the latter, 1,012 could be classified on the basis of findings in screening and diagnostic mammograms, consisting of 489 true interval cancers (48.2%), 235 false-negatives (23.2%), 172 minimal-signs (17.2%) and 114 occult tumors (11.3%). Information on the screening protocol and women''s characteristics were obtained from the screening program registry. Cause-specific Cox regression models were used to estimate the hazard ratios (HR) of risks factors for interval cancer and incident screen-detected cancer. A multinomial regression model, using screen-detected tumors as a reference group, was used to assess the effect of breast density and other factors on the occurrence of interval cancer subtypes.

Results

A previous false-positive was the main risk factor for interval cancer (HR = 2.71, 95%CI: 2.28–3.23); this risk was higher for false-negatives (HR = 8.79, 95%CI: 6.24–12.40) than for true interval cancer (HR = 2.26, 95%CI: 1.59–3.21). A family history of breast cancer was associated with true intervals (HR = 2.11, 95%CI: 1.60–2.78), previous benign biopsy with a false-negatives (HR = 1.83, 95%CI: 1.23–2.71). High breast density was mainly associated with occult tumors (RRR = 4.92, 95%CI: 2.58–9.38), followed by true intervals (RRR = 1.67, 95%CI: 1.18–2.36) and false-negatives (RRR = 1.58, 95%CI: 1.00–2.49).

Conclusion

The role of women''s characteristics differs among interval cancer subtypes. This information could be useful to improve effectiveness of breast cancer screening programmes and to better classify subgroups of women with different risks of developing cancer.     

Effect of age, family history of prostate cancer, prostate enlargement and seasonality on PSA levels in a contemporary cohort of healthy Italian subjects

We assessed the joint effect of age at enrollment, age at follow-up, family history of prostate cancer, prostate enlargement and seasonality on prostate-specific antigen (PSA) estimated through log-normal mixed-effects modeling in an Italian cohort of healthy, 45- to 65-year-old subjects over a 4-year period. The median ratio was used as the measure of effect. Median and mean baseline PSA were 0.78 (interquartile range: 0.41-1.50) and 1.27 (95% CI: 1.19-1.35) ng/mL, respectively. A similar median annual increase of 5.7% (95% CI: 4.8%-6.5%) was found for age at enrollment and age at follow-up. Individuals with moderate to severe prostate enlargement had a median PSA ratio of 1.040 (95% CI: 0.919-1.176) and 1.318 (95% CI: 1.128-1.539), respectively. Median ratios of 1.200 (95% CI: 0.026-1.404) and 1.300 (95% CI: 0.915-1.845), respectively, were computed for subjects with only one or more than one prostate-cancer-affected relatives. Regarding seasonality, the highest value was shown in summertime, the lowest in wintertime, and the resulting median ratio was 1.280 (95% CI: 1.117-1.468). Irrespective of age, baseline PSA was in most cases about 1.00 ng/mL with a yearly median variation of about 5% over a 4-year period. Indeed, prostate enlargement, prostate cancer family history and seasonality showed a remarkable impact on PSA measurement. This should be considered when counseling patients with a PSA history.     

Screening Coverage Needed to Reduce Mortality from Prostate Cancer: A Living Systematic Review

IntroductionScreening for prostate cancer remains controversial because of conflicting results from the two major trials: The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC).ObjectiveMeta-analyze and meta-regress the available PSA screening trials.MethodsWe performed a living systematic review and meta-regression of the reduction in prostate cancer mortality as a function of the duration of screening provided in each trial. We searched PubMed, Web of Science, the Cochrane Registry, and references lists from previous meta-analyses to identify randomized trials of PSA screening. We followed PRISMA guidelines and qualified strength of evidence with a GRADE Profile.ResultsWe found 6 trials, but excluded one that also screened with trans-rectal ultrasound. We considered each ERSPC center as a separate trial. When pooling together all 11 trials we found no significant benefit from screening; however, the heterogeneity was 28.2% (95% CI: 0% to 65%). Heterogeneity was explained by variations in the duration of serial screening (I² 0%; 95% CI: 0% to 52%). When we analyzed the subgroup of trials that added more than 3 years of screening (range 3.2 to 3.8) we found a significant benefit for screening with risk ratio 0.78 (95% CI 0.65–0.94; I² = 0%; 95% CI: 0% to 69%) and a number needed to invite for screening of 1000. We downgraded the quality of evidence to moderate due to our retrospective identification of subgroups and limited data on control group screening.ConclusionsAdequate duration of screening reduces mortality from prostate cancer. The benefit, while small, compares favorably with screening for other cancers. Our projections are limited by the moderate quality of evidence.     

The Risk of Cancer in Patients with Generalized Anxiety Disorder: A Nationwide Population-Based Study

Objective

To evaluate the risk of cancer among patients with generalized anxiety disorder (GAD) in a nationwide population-based dataset.

Methods

We recruited newly-diagnosed GAD patients aged 20 years or older without antecedent cancer from the Taiwan National Health Insurance Research database between 2000–2010. Standardized incidence ratios (SIRs) of cancers were calculated in GAD patients, and the subgroup of GAD patients diagnosed by psychiatric specialists.

Results

A total of 559 cancers developed among 19,793 GAD patients with a follow-up of 89,485 person-years (median follow-up of 4.34 years), leading to a significantly increased SIR of 1.14 [95% confidence interval (CI) 1.05–1.24]. Male GAD patients had a significantly increased SIR overall (1.30, 95% CI 1.15–1.46) and for lung and prostate cancer (1.77, 95% CI 1.33–2.30 and 2.17, 95% CI 1.56–2.93, respectively). Patients over 80 years of age also had a significantly increased SIR (1.56, 95% CI 1.25–1.92), especially in males. However, psychiatrist-diagnosed GAD patients did not show increased cancer risk relative to the general population, perhaps due to having fewer physical comorbidities than non-psychiatrist-diagnosed GAD patients.

Conclusion

This study found that overall cancer risk is elevated among patients with GAD. The risk of lung and prostate cancer also increased in male patients with GAD. This increased cancer risk may be due to physical comorbidities and surveillance bias. Further prospective study is necessary to confirm these findings.     

Prostate cancer in elderly men

Due to increasing life expectancy and the introduction of prostate-specific antigen (PSA) screening, a rising number of elderly men are diagnosed with prostate cancer. Besides PSA serum levels and Gleason score, age is considered to be a key prognostic factor in terms of treatment decisions. In men older than 70 years, treatment without curative intent may deprive the frail patient of years of life. Modern radical prostatectomy techniques are associated with low perioperative morbidity, excellent clinical outcome, and documented long-term disease control. Thus, radical prostatectomy should be considered because local treatment of organ-confined prostate cancer potentially cures disease. The huge extent of PSA screening programs may lead to overdiagnosis of prostate cancer. Not every man who is diagnosed with prostate cancer will develop clinically significant disease. This has led to the concept of expectant management for screen-detected, small-volume, low-grade disease, with the intention of providing therapy for those men with disease progression.     

The validity of cancer information on death certificates in Norway and the impact of death certificate initiated cases on cancer incidence and survival

BackgroundDeath certificates are an important source of information for cancer registries. The aim of this study was to validate the cancer information on death certificates, and to investigate the effect of including death certificate initiated (DCI) cases in the Cancer Registry of Norway when estimating cancer incidence and survival.MethodsAll deaths in Norway in the period 2011–2015 with cancer mentioned on the death certificates were linked to the cancer registry. Notifications not registered from other sources were labelled death certificate notifications (DCNs), and considered as either cancer or not, based on available information in the registry or from trace-back to another source.ResultsFrom the total of 65 091 cancers mentioned on death certificates in the period 2011–2015, 58,425 (89.8%) were already in the registry. Of the remaining 6 666 notifications, 2 636 (2 129 with cancer as underlying cause) were not regarded to be new cancers, which constitutes 4.0% of all cancers mentioned on death certificates and 39.5% of the DCNs. Inclusion of the DCI cases increased the incidence of all cancers combined by 2.6%, with largest differences for cancers with poorer prognosis and for older age groups. Without validation, including the 2 129 disregarded death certificates would over-estimate the incidence by 1.3%. Including DCI cases decreased the five-year relative survival estimate for all cancer sites combined with 0.5% points.ConclusionIn this study, almost 40% of the DCNs were regarded not to be a new cancer case, indicating unreliability of death certificate information for cancers that are not already registered from other sources. The majority of the DCNs where, however, registered as new cases that would have been missed without death certificates. Both including and excluding the DCI cases will potentially bias the survival estimates, but in different directions. This biases were shown to be small in the Cancer Registry of Norway.     

Deprivation and mass screening: Survival of women diagnosed with breast cancer in France from 2008 to 2010

BackgroundSome studies have investigated the role of socio-demographic inequalities in the association between screening and survival. However, in France, no study has been conducted to describe the socio-demographic characteristics and survival of women with breast cancer based on their participation to mass screening. The aim of this study was to assess the impact of socio-demographic inequalities on the association between participation in mass screening program and survival of women with breast cancer.MethodsData for 2,244 women aged 50–74 years diagnosed with breast cancer over the period 2008–2010 were obtained from the cancer registry and the screening structure of Gironde. We used the aggregated European Deprivation Index (EDI) to define the deprivation level of women. Net survival rates were estimated with the Pohar-Perme method, with and without correcting for lead-time bias.ResultsSurvival rates were lower for non-attenders than for screen-detected women (83.8% vs 97.3%, p < 0.0001), even after correcting for lead-time bias. Among the most deprived women, the survival rate was significantly different between non-attenders and screen-detected women (78.1% vs 95.6%, p = 0.0002), suggesting an important effect of mass screening in this group.ConclusionThe introduction of incentive actions in deprived areas could play a key role in the adherence of women to mass screening and in improving their survival in case of a breast cancer diagnosis.