Breast cancer survival and prognosis by screening history

Background:

Cancers not detected by breast screening are commonly assumed to have poorer prognosis.

Methods:

We examined the survival experience of all women aged 50–74 years diagnosed with a first breast cancer between 1998 and 2006 in British Columbia, Canada and determined their screening experience. Disease-specific survival rates were calculated and, for cases diagnosed in 2002, prognostic factors (size, nodal involvement, grade ER status and stage) were examined by time since screening.

Results:

Breast cancers diagnosed at screening had the best survival (P<0.001). Cancers detected within 12 months of a negative screen had similar survival rates (P=0.98) to those diagnosed within 12–23 and 24–47 months, with other non-screen-detected cancers having poorer survival (P<0.001). The prognostic profile of cancers diagnosed in 2002 followed a similar pattern.

Interpretation:

There was no evidence that cancers diagnosed within 12 months had poorer prognosis than those diagnosed up to 48 months following screening.     

Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes

Background:

Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early.

Methods:

Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women with no known pelvic mass.

Results:

Twenty-two miRNAs were differentially expressed between healthy controls and the ovarian cancer group (P<0.05), while a six miRNA profile subset distinguished presurgical plasma from benign and ovarian cancer patients. There were also significant differences in miRNA profiles in presurgical plasma from women diagnosed with ovarian cancer who had short overall survival when compared to women with long overall survival (P<0.05).

Conclusion:

Our preliminary data support the utility of circulating plasma miRNAs to distinguish women with ovarian cancer from those with a benign mass and identify women likely to benefit from currently available treatment for serous epithelial ovarian cancer from those who may not.     

Socioeconomic inequalities in cancer survival in England after the NHS cancer plan

Background:

Socioeconomic inequalities in survival were observed for many cancers in England during 1981–1999. The NHS Cancer Plan (2000) aimed to improve survival and reduce these inequalities. This study examines trends in the deprivation gap in cancer survival after implementation of the Plan.

Materials and method:

We examined relative survival among adults diagnosed with 1 of 21 common cancers in England during 1996–2006, followed up to 31 December 2007. Three periods were defined: 1996–2000 (before the Cancer Plan), 2001–2003 (initialisation) and 2004–2006 (implementation). We estimated the difference in survival between the most deprived and most affluent groups (deprivation gap) at 1 and 3 years after diagnosis, and the change in the deprivation gap both within and between these periods.

Results:

Survival improved for most cancers, but inequalities in survival were still wide for many cancers in 2006. Only the deprivation gap in 1-year survival narrowed slightly over time. A majority of the socioeconomic disparities in survival occurred soon after a cancer diagnosis, regardless of the cancer prognosis.

Conclusion:

The recently observed reduction in the deprivation gap was minor and limited to 1-year survival, suggesting that, so far, the Cancer Plan has little effect on those inequalities. Our findings highlight that earlier diagnosis and rapid access to optimal treatment should be ensured for all socioeconomic groups.     

Changing presentation of prostate cancer in a UK population – 10 year trends in prostate cancer risk profiles in the East of England

Background:

Prostate cancer incidence is rising in the United Kingdom but there is little data on whether the disease profile is changing. To address this, we interrogated a regional cancer registry for temporal changes in presenting disease characteristics.

Methods:

Prostate cancers diagnosed from 2000 to 2010 in the Anglian Cancer Network (n=21 044) were analysed. Risk groups (localised disease) were assigned based on NICE criteria. Age standardised incidence rates (IRs) were compared between 2000–2005 and 2006–2010 and plotted for yearly trends.

Results:

Over the decade, overall IR increased significantly (P<0.00001), whereas metastasis rates fell (P<0.0007). For localised disease, IR across all risk groups also increased but at different rates (P<0.00001). The most striking change was a three-fold increase in intermediate-risk cancers. Increased IR was evident across all PSA and stage ranges but with no upward PSA or stage shift. In contrast, IR of histological diagnosis of low-grade cancers fell over the decade, whereas intermediate and high-grade diagnosis increased significantly (P<0.00001).

Conclusion:

This study suggests evidence of a significant upward migration in intermediate and high-grade histological diagnosis over the decade. This is most likely to be due to a change in histological reporting of diagnostic prostate biopsies. On the basis of this data, increasing proportions of newly diagnosed cancers will be considered eligible for radical treatment, which will have an impact on health resource planning and provision.     

Serum lactate dehydrogenase and survival following cancer diagnosis

Background:

There is evidence that high level of serum lactate dehydrogenase (LDH) is associated with poorer overall survival in several malignancies, but its link to cancer-specific survival is unclear.

Methods:

A total of 7895 individuals diagnosed with cancer between 1986 and 1999 were selected for this study. Multivariable Cox proportional hazards regression was used to assess overall and cancer-specific death by the z-score and clinical categories of serum LDH prospectively collected within 3 years before diagnosis. Site-specific analysis was performed for major cancers. Analysis was repeated by different lag times between LDH measurements and diagnosis.

Results:

At the end of follow-up, 5799 participants were deceased. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cancer-specific death in the multivariable model were 1.43 (1.31–1.56) and 1.46 (1.32–1.61), respectively, for high compared with low prediagnostic LDH. Site-specific analysis showed high LDH to correlate with an increased risk of death from prostate, pulmonary, colorectal, gastro-oesophageal, gynaecological and haematological cancers. Serum LDH assessed within intervals closer to diagnosis was more strongly associated with overall and cancer-specific death.

Conclusions:

Our findings demonstrated an inverse association of baseline serum LDH with cancer-specific survival, corroborating its role in cancer progression.     

Inflammation as a validated prognostic determinant in carcinoma of unknown primary site

Background:

Carcinoma of unknown primary (CUP) is a clinical presentation with a poor prognosis. Inflammation-based prognostic systems are stage-independent prognostic predictors in various malignancies. We aimed to assess the accuracy of the modified Glasgow Prognostic Score (mGPS), neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) as objective prognostic models in CUP.

Methods:

We derived inflammatory scores in 60 consecutive CUP referrals to the Imperial College oncology unit between 1996 and 2011. Patient demographics, treatment and staging data and full blood profiles were collected. An independent cohort of 179 patients presenting to the Taipei Veterens Hospital between 2000 and 2009 were used as a ‘validation'' data set. Uni- and multivariate survival analysis was used to predict the overall survival (OS).

Results:

Sixty patients were included: median age 61 (range: 33–86); 51% men; median OS 5.9 months (0.7–42.9); 88% with distant metastases. On univariate analysis NLR >5 (P=0.04) and mGPS (score 1–2) (P=0.03) correlated with OS. Multivariate analysis demonstrated significant hazard ratios for NLR; 2.02 (CI 1.0–4.1) (P=0.04) and mGPS; 1.52 (CI 1.0–2.3) (P=0.03). These findings were reinforced by analysis of the validation data.

Conclusion:

NLR and mGPS are independent, externally validated prognostic markers in CUP, with superior objectivity compared with performance status.     

An evaluation of the impact of large-scale interventions to raise public awareness of a lung cancer symptom

Introduction:

Long-term lung cancer survival in England has improved little in recent years and is worse than many countries. The Department of Health funded a campaign to raise public awareness of persistent cough as a lung cancer symptom and encourage people with the symptom to visit their GP. This was piloted regionally within England before a nationwide rollout.

Methods:

To evaluate the campaign''s impact, data were analysed for various metrics covering public awareness of symptoms and process measures, through to diagnosis, staging, treatment and 1-year survival (available for regional pilot only).

Results:

Compared with the same time in the previous year, there were significant increases in metrics including: public awareness of persistent cough as a lung cancer symptom; urgent GP referrals for suspected lung cancer; and lung cancers diagnosed. Most encouragingly, there was a 3.1 percentage point increase (P<0.001) in proportion of non-small cell lung cancer diagnosed at stage I and a 2.3 percentage point increase (P<0.001) in resections for patients seen during the national campaign, with no evidence these proportions changed during the control period (P=0.404, 0.425).

Conclusions:

To our knowledge, the data are the first to suggest a shift in stage distribution following an awareness campaign for lung cancer. It is possible a sustained increase in resections may lead to improved long-term survival.     

Screen-detected colorectal cancers are associated with an improved outcome compared with stage-matched interval cancers

Background:

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.

Methods:

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.

Results:

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.

Conclusions:

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.     

The risk of a subsequent cancer diagnosis after herpes zoster infection: primary care database study

Background:

Herpes zoster and cancer are associated with immunosuppression. Zoster occurs more often in patients with an established cancer diagnosis. Current evidence suggests some risk of cancer after zoster but is inconclusive. We aimed to assess the risk of cancer following zoster and the impact of prior zoster on cancer survival.

Methods:

A primary care database retrospective cohort study was undertaken. Subjects with zoster were matched to patients without zoster. Risk of cancer following zoster was assessed by generating hazard ratios using Cox regression. Time to cancer was generated from the index date of zoster diagnosis.

Results:

In total, 2054 cancers were identified in 74 029 patients (13 428 zoster, 60 601 matches). The hazard ratio for cancer diagnosis after zoster was 2.42 (95% confidence interval 2.21, 2.66) and the median time to cancer diagnosis was 815 days. Hazard ratios varied between cancers, and were highest in younger patients. There were more cancers in patients with zoster than those without for all age groups and both genders. Prior immunosuppression was not associated with change in risk, and diagnosis of zoster before cancer did not affect survival.

Conclusion:

This study establishes an association between zoster and future diagnosis of cancer having implications for cancer case finding after zoster diagnosis.     

Cancer survival differences between South Asians and non-South Asians of England in 1986–2004, accounting for age at diagnosis and deprivation

Background:

South Asian migrants show lower cancer incidence than their host population in England for most major cancers. We seek to study the ethnic differences in survival from cancer.

Methods:

We described and modelled the effect of ethnicity, time, age and deprivation on survival for the five most incident cancers in each sex in South Asians in England between 1986 and 2004 using national cancer registry data. South Asian ethnicity was flagged using the validated name-recognition algorithm SANGRA (South Asian Names and Group Recognition Algorithm).

Results:

We observed survival advantage in South Asians in earlier periods. This ethnic gap either remained constant or narrowed over time. By 2004, age-standardised net survival was comparable for all cancers except three in men, where South Asians had higher survival 5 years after diagnosis: colorectal (58.9% vs 53.6%), liver (15.0% vs 9.4%) and lung (15.9% vs 9.3%). Compared with non-South Asians, South Asians experienced a slower increase in breast and prostate cancer survival, both cancers associated with either a screening programme or an early diagnosis test. We did not find differential patterns in survival by deprivation between both ethnicities.

Conclusions:

Considering recent survival trends, appropriate action is required to avoid deficits in cancer survival among South Asians in the near future.     

High-temperature-required protein A2 as a predictive marker for response to chemotherapy and prognosis in patients with high-grade serous ovarian cancers

Background:

High-temperature-required protein A2 (HtrA2), a protein relating with apoptosis in a caspases-dependent and non-dependent manner, has been reported to be associated with chemosensitivity in several human cancers.

Methods:

Tissue microarrays made from 142 patients with high-grade serous ovarian adenocarcinoma were evaluated to assess whether HtrA2 expression was related with several clinical parameters.

Results:

Negative HtrA2 expression was observed in 36 cases (25%) of the patients, and related with significantly lower response rates of primary chemotherapy than those with positive HtrA2 expression (56% vs 83%, P<0.01). In addition, negative HtrA2 expression was identified as an independent worse prognostic factor for progression-free survival and overall survival by multivariate analyses. Furthermore, HtrA2 downregulation modulated sensitivity to platinum in serous ovarian cancer cells in vitro.

Conclusions:

HtrA2 expression was a predictor for sensitivity to chemotherapy, and could be a candidate of molecular target in the treatment of high-grade serous ovarian cancers.     

Cancer prevalence in United States,Nordic Countries,Italy, Australia,and France: an analysis of geographic variability

Background:

The objectives of this study were to quantitatively assess the geographic heterogeneity of cancer prevalence in selected Western Countries and to explore the associations between its determinants.

Methods:

For 20 cancer sites, 5-year cancer prevalence, incidence, and survival were observed and age standardised for the mid 2000s in the United States, Nordic European Countries, Italy, Australia, and France.

Results:

In Italy, 5-year crude prevalence for all cancers was 1.9% in men and 1.7% in women, while it was ∼1.5% in all other countries and sexes. After adjustment for the different age distribution of the populations, cancer prevalence in the United States was higher (20% in men and 10% in women) than elsewhere. For all cancers combined, the geographic heterogeneities were limited, though relevant for specific cancers (e.g., prostate, showing >30% higher prevalence in the United States, or lung, showing >50% higher prevalence in USA women than in other countries). For all countries, the correlations between differences of prevalence and differences of incidence were >0.9, while prevalence and survival were less consistently correlated.

Conclusion:

Geographic differences and magnitude of crude cancer prevalence were more strongly associated with incidence rates, influenced by population ageing, than with survival rates. These estimates will be helpful in allocating appropriate resources.     

Age, gender, and racial differences in incidence and survival in primary CNS lymphoma

Background:

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma that accounts for ∼4% of newly diagnosed central nervous system (CNS) tumours. The objective of this study was to analyse the epidemiology, incidence, and outcome of these rare tumours.

Methods:

Primary brain and CNS lymphoma cases were identified from the Surveillance, Epidemiology, and End Results (SEER) research data sets for the years 1980–2008 for analysis of trends in incidence and survival. SEER^*Stat v. 7.0.4 software was used to analyse the data.

Results:

The overall incidence rate of PCNSL was 0.47 per 100 000 person-years. The incidence was significantly higher in males compared with females, blacks aged 0–49 years at diagnosis compared with whites, and whites aged 50 years and older at diagnosis compared with blacks. After a significant decline in incidence between 1995 and 1999, incidence rates rose slightly; those aged 75+ years at diagnosis had the most dramatic increase in incidence rates over time. Five-year survival rates were significantly higher in whites compared with blacks aged 0–49 years at diagnosis, but was primarily driven by white women aged 0–49 years.

Conclusion:

There is an increase in incidence of PCNSL in the elderly, and elderly blacks have lower incidence compared with white population. Survival remains poor and is negatively dominated by factors associated with HIV infection and advanced age.     

Spectrum of very early breast cancer in a setting without organised screening

Background:

Within a setting without organised breast cancer screening, the characteristics and survival of very early breast cancer were determined.

Methods:

All 4930 women diagnosed with breast cancer in University Malaya Medical Center, Malaysia from 1993 to 2011 were included. Factors associated with very early presentation (stage I) at diagnosis were identified. Tumour characteristics, management patterns, and survival of very early breast cancer were described, and where appropriate, compared with other settings.

Results:

Proportion of women presenting with stage I breast cancer significantly increased from 15.2% to 25.2% over two decades. Factors associated with very early presentation were Chinese ethnicity, positive family history of breast cancer, and recent period of diagnosis. Within stage I breast cancers, median tumour size at presentation was 1.5 cm. A majority of stage I breast cancer patients received mastectomy, which was associated with older age, Chinese ethnicity, postmenopausal status, and larger tumours. Chemotherapy was administered in 36% of patients. Five-year age-adjusted relative survival for women with stage I breast cancer was 99.1% (95% CI: 97.6–99.6%).

Conclusions:

The proportion of women presenting with very early breast cancer in this setting without organised screening is increasing. These women seem to survive just as well as their counterparts from affluent settings.     

Is England closing the international gap in cancer survival?

Background:

We provide an up-to-date international comparison of cancer survival, assessing whether England is ‘closing the gap'' compared with other high-income countries.

Methods:

Net survival was estimated using national, population-based, cancer registrations for 1.9 million patients diagnosed with a cancer of the stomach, colon, rectum, lung, breast (women) or ovary in England during 1995–2012. Trends during 1995–2009 were compared with estimates for Australia, Canada, Denmark, Norway and Sweden. Clinicians were interviewed to help interpret trends.

Results:

Survival from all cancers remained lower in England than in Australia, Canada, Norway and Sweden by 2005–2009. For some cancers, survival improved more in England than in other countries between 1995–1999 and 2005–2009; for example, 1-year survival from stomach, rectal, lung, breast and ovarian cancers improved more than in Australia and Canada. There has been acceleration in lung cancer survival improvement in England recently, with average annual improvement in 1-year survival rising to 2% during 2010–2012. Survival improved more in Denmark than in England for rectal and lung cancers between 1995–1999 and 2005–2009.

Conclusions:

Survival has increased in England since the mid-1990s in the context of strategic reform in cancer control, however, survival remains lower than in comparable developed countries and continued investment is needed to close the international survival gap.     

Routes to diagnosis for cancer – determining the patient journey using multiple routine data sets

Background:

Cancer survival in England is lower than the European average, which has been at least partly attributed to later stage at diagnosis in English patients. There are substantial regional and demographic variations in cancer survival across England. The majority of patients are diagnosed following symptomatic or incidental presentation. This study defines a methodology by which the route the patient follows to the point of diagnosis can be categorised to examine demographic, organisational, service and personal reasons for delayed diagnosis.

Methods:

Administrative Hospital Episode Statistics data are linked with Cancer Waiting Times data, data from the cancer screening programmes and cancer registration data. Using these data sets, every case of cancer registered in England, which was diagnosed in 2006–2008, is categorised into one of eight ‘Routes to Diagnosis''.

Results:

Different cancer types show substantial differences between the proportion of cases that present by each route, in reasonable agreement with previous clinical studies. Patients presenting via Emergency routes have substantially lower 1-year relative survival.

Conclusion:

Linked cancer registration and administrative data can be used to robustly categorise the route to a cancer diagnosis for all patients. These categories can be used to enhance understanding of and explore possible reasons for delayed diagnosis.     

Association between tuberculosis infections and non-pulmonary malignancies: a nationwide population-based study

Background:

In addition to lung cancers, tuberculosis infections have been associated with increased risk of non-pulmonary malignancies in case reports. Our population-based study employed standardized incidence ratios (SIRs) to systemically survey non-pulmonary cancer risks after tuberculosis infections.

Methods:

Data of patients who had newly diagnosed tuberculosis, were aged 20 years or older, and had no prior cancer or tuberculosis were sampled from the Taiwan National Health Insurance database between 2000 and 2010. SIRs compared cancer incidence in patients with tuberculosis infections to the general population. SIRs of specific cancers were further analyzed with respect to gender and time after tuberculosis infections.

Results:

After a follow-up period of 28 866 person–years, 530 tuberculosis cases developed cancers compared with 256 cases in the general populations (2.07, 95% confidence interval (CI), 1.90–2.26). The SIR of non-pulmonary malignancies was also increased (1.71, 95% CI, 1.54–1.90). For males, SIRs were increased within 1 year after tuberculosis diagnosis for the following cancers: head and neck, esophageal, colorectal, liver, lung, melanomas, and Hodgkin''s disease. SIRs were increased for liver, biliary, lung, and bladder cancers beyond the first year after tuberculosis diagnosis. For females, SIRs were increased for leukemia, esophageal, and lung cancers within the first year, and only for leukemia beyond 1 year post diagnosis.

Conclusion:

Having found increased risks of several cancers that differ with gender and time after tuberculosis diagnosis, physicians may consider these factors in patients following tuberculosis diagnosis.     

Diabetes and pancreatic cancer survival: a prospective cohort-based study

Background:

Diabetes is a risk factor for pancreatic cancer but its association with survival from pancreatic cancer is poorly understood. Our objective was to investigate the association of diabetes with survival among pancreatic cancer patients in a prospective cohort-based study where diabetes history was ascertained before pancreatic cancer diagnosis.

Methods:

We evaluated survival by baseline (1993–2001) self-reported diabetes history (n=62) among 504 participants that developed exocrine pancreatic cancer within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using Cox proportional hazards model, adjusted for age, sex, body mass index, race, smoking, and tumour stage (local, locally advanced, and metastatic).

Results:

The multivariable-adjusted HR for mortality comparing participants with diabetes to those without was 1.52 (95% CI=1.14–2.04, P-value <0.01). After excluding those diagnosed with pancreatic cancer within 3 years of study enrolment, HR for mortality among those with diabetes was 1.45 (95% CI=1.06–2.00, P-value=0.02).

Conclusions:

Using prospectively collected data, our findings indicate that diabetes is associated with worse survival among patients with pancreatic cancer.     

Investigation of low 5-year relative survival for breast cancer in a London cancer network

Background:

Breast cancer 5-year relative survival is low in the North East London Cancer Network (NELCN).

Methods:

We compared breast cancer that was diagnosed during 2001–2005 with that in the rest of London.

Results:

North East London Cancer Network women more often lived in socioeconomic quintile 5 (42 vs 21%) and presented with advanced disease (11 vs 7%). Cox regression analysis showed the survival difference (hazard ratio: 1.27, 95% confidence interval (CI): 1.15–1.41) reduced to 1.00 (95% CI: 0.89–1.11) after adjustment for age, stage, socioeconomic deprivation, ethnicity and treatment. Major drivers were stage and deprivation. Excess mortality was in the first year.

Conclusion:

Late diagnosis occurs in NELCN.     

Trends in the lifetime risk of developing cancer in Great Britain: comparison of risk for those born from 1930 to 1960

Background:

Typically, lifetime risk is calculated by the period method using current risks at different ages. Here, we estimate the probability of being diagnosed with cancer for individuals born in a given year, by estimating future risks as the cohort ages.

Methods:

We estimated the lifetime risk of cancer in Britain separately for men and women born in each year from 1930 to 1960. We projected rates of all cancers (excluding non-melanoma skin cancer) and of all cancer deaths forwards using a flexible age-period-cohort model and backwards using age-specific extrapolation. The sensitivity of the estimated lifetime risk to the method of projection was explored.

Results:

The lifetime risk of cancer increased from 38.5% for men born in 1930 to 53.5% for men born in 1960. For women it increased from 36.7 to 47.5%. Results are robust to different models for projections of cancer rates.

Conclusions:

The lifetime risk of cancer for people born since 1960 is >50%. Over half of people who are currently adults under the age of 65 years will be diagnosed with cancer at some point in their lifetime.