An updated report on the incidence and epidemiological trends of keratinocyte cancers in the United Kingdom 2013-2018.

Introduction: The most common cancers in the UK are keratinocyte cancers (KCs): the combined term for basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Registration of KC is challenging due to high numbers and multiplicity of tumours per person. Methods: We provide an updated report on the descriptive epidemiology of trends in KC incidence for the resident populations of UK countries (England, Northern Ireland, Scotland and Wales) using population-based cancer registry and pathology report data, 2013-18. Results: Substantial increases in cSCC incidence in England, Scotland and Northern Ireland can be detected for the period of 2013-18, and the incidence of cSCC also increased in Wales from 2016 to 2018. In contrast, however, the pattern of annual change in the incidence of BCC across the nations differs. In England, the incidence of BCC declined slightly from 2016 to 2018, however, the overall trend across 2013-18 is not statistically significant. In Scotland, the incidence of BCC shows some variability, declining in 2017 before increasing in 2018, and the overall trend across 2013-18 was also not statistically significant. In Northern Ireland, the incidence of BCC increased significantly over the study period, and in Wales, the incidence of BCC increased from 2016 to 2018. One in five people will develop non-melanoma skin cancers (NMSC) in their lifetime in England. This estimate is much higher than the lifetime risk of melanoma (1 in 36 males and 1 in 47 females born after 1960 in the UK), which further highlights the burden of the disease and importance of early prevention strategies. Conclusions: We highlight how common these tumours are by publishing the first ever lifetime incidence of NMSC. Additionally, the first time reporting of the age standardised incidence of KC in Wales further confirms the scale of the disease burden posed by these cancers in the UK. With approximately one in five people developing NMSC in their lifetime, optimisation of skin cancer prevention, management and research are essential.

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.

What is the lifetime risk of developing cancer?: the effect of adjusting for multiple primaries.

BACKGROUND: The 'lifetime risk' of cancer is generally estimated by combining current incidence rates with current all-cause mortality ('current probability' method) rather than by describing the experience of a birth cohort. As individuals may get more than one type of cancer, what is generally estimated is the average (mean) number of cancers over a lifetime. This is not the same as the probability of getting cancer. METHODS: We describe a method for estimating lifetime risk that corrects for the inclusion of multiple primary cancers in the incidence rates routinely published by cancer registries. The new method applies cancer incidence rates to the estimated probability of being alive without a previous cancer. The new method is illustrated using data from the Scottish Cancer Registry and is compared with 'gold-standard' estimates that use (unpublished) data on first primaries. RESULTS: The effect of this correction is to make the estimated 'lifetime risk' smaller. The new estimates are extremely similar to those obtained using incidence based on first primaries. The usual 'current probability' method considerably overestimates the lifetime risk of all cancers combined, although the correction for any single cancer site is minimal. CONCLUSION: Estimation of the lifetime risk of cancer should either be based on first primaries or should use the new method.

Cancer survival in England and the influence of early diagnosis: what can we learn from recent EUROCARE results?

BACKGROUND: This review of the EUROCARE-4 results attempts to separate out the early and late mortality effects contributing to the widely reported poorer 5-year survival rates for cancer patients in the United Kingdom compared with other European countries for 26 cancer sites. METHODS: Patients diagnosed with cancer in 1996-1999 in 23 European countries were included in the analyses. Comparison of 1-year, 5-year and 5|1-year (i.e. only including those patients who had survived to 1 year) survival estimates between data for England and the 'European average' was undertaken. This analysis was to highlight the relative contribution of early diagnosis, using 1-year survival as a proxy measure, on 5-year survival for the different sites of cancer. Three groups of cancer sites were identified according to whether the survival differences at 1, 5 and 5|1-years were statistically significant. RESULTS AND CONCLUSIONS: Breast cancer showed significantly poorer 1- and 5-year survival estimates in England, but the 5|1-year survival figure was not significantly different. Thus, successful initiatives around awareness and early detection could eradicate the survival gap. In contrast, the 5|1-year survival estimates remained significantly worse for lung, colorectal and prostate cancers, showing that although early detection could make some difference, late effects such as treatment and management of the patients were also influencing long-term outcome differences between England and Europe.

Postoperative wound complications and systemic recurrence in breast cancer.

Many factors involved in wound healing can stimulate tumour growth in the experimental setting. This study examined the relationship between wound complications and the development of systemic recurrence after treatment of primary breast cancer. One thousand and sixty-five patients diagnosed with operable primary invasive breast cancer between 1994 and 2001 were assessed for development of systemic recurrence according to whether or not a wound complication occurred after surgery, with a median follow-up of 54 months (range 15-119). There were 93 wound complications (9%). There was a statistically significant greater risk of developing systemic recurrence in patients with wound problems than those without (hazard ratio (HR) 2.87; 95% CI: 1.97, 4.18; P<0.0001). This remained in a multivariate analysis after adjustment for case mix variables, including Nottingham Prognostic Index (NPI) and oestrogen-progesterone receptor status (HR: 2.52; 95% CI: 1.69, 3.77; P<0.0001). In the good prognostic NPI group, 4 out of 27 patients (15%) with wound problems vs 11 out of 334 (3%) without wound problems developed systemic recurrence. The corresponding figures were 10 out of 35 (29%) vs 48 out of 412 (12 %) in the moderate prognostic group and 18 out of 29 (62%) vs 75 out of 199 (38%) in the poor prognostic group. In 29 patients NPI could not be calculated. Smokers at the time of diagnosis were more likely to develop metastatic disease than the non-smokers (HR: 1.50; 95% CI: 1.04, 2.15; P=0.03) after adjustment for other factors. The results suggest that patients with wound complications at primary surgery have increased rates of systemic recurrence of breast cancer.

Radiotherapy following breast-conserving surgery for screen-detected ductal carcinoma in situ: indications and utilisation in the UK. Interim findings from the Sloane Project.

Use of radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) varies according to country, precedent and prejudice. Results from a preliminary analysis of the data available within the UK Sloane Project can be appreciated in the context of the uncertainty concerning the selection of adjuvant RT following BCS for DCIS. There was a marked geographical variation in the use of RT within the United Kingdom. However, overall, patients with DCIS treated with BCS were significantly more likely to have RT planned (and given) if they had large (> or =15 mm), intermediate or high-grade tumours or if central comedo-type necrosis was present. Unexpectedly, margin width did not appear to have a significant effect on the decision-making process. However, the Van Nuys Prognostic Index did significantly affect the chances of getting planned RT in the univariate analysis, suggesting that clinicians may be starting to use this scoring system in routine practice to assist in decision making.

Second primary malignancies after treatment for malignant lymphoma.

To determine the incidence and possible causes of second primary malignancies after treatment for Hodgkin's and Non-Hodgkin's lymphoma (HL and NHL). A cohort of 3764 consecutive patients diagnosed with HL or NHL between January 1970 and July 2001 was identified using the Sheffield Lymphoma Group database. A search was undertaken for all patients diagnosed with a subsequent primary malignancy. Two matched controls were identified for each case. Odds ratios were calculated to detect and quantify any risk factors in the cases compared to their matched controls. Mean follow-up for the cohort was 5.2 years. A total of 68 patients who developed second cancers at least 6 months after their primary diagnosis were identified, giving a crude incidence of 1.89% overall: 3.21% among the patients treated for HL, 1.32% in those treated for NHL. Most common were bronchial, breast, colorectal and haematological malignancies. High stage at diagnosis almost reached statistical significance in the analysis of just the NHL patients (odds ratio = 3.48; P = 0.068) after adjustment for other factors. Treatment modality was not statistically significant in any analysis. High stage at diagnosis of NHL may be a risk factor for developing a second primary cancer.

Improvements in survival for women with breast cancer in Scotland between 1987 and 1993: impact of earlier diagnosis and changes in treatment.

We investigated changes in survival, and their causes, in women with early breast cancer diagnosed in Scotland. The Scottish Cancer Registry identified 1617 and 2077 such women, without metastases at diagnosis who underwent surgery as part of their primary treatment, diagnosed in 1987 and 1993, respectively. There was a statistically significant 11% improvement in 8-year survival between 1987 and 1993. Survival improved across almost all clinical/pathological, treatment and health care delivery/deprivation categories; improvement was not limited to those women diagnosed through the screening programme. In a multivariate model, improved survival appeared to be explained largely by screening and clinical/pathological prognostic factors. Deprivation also had an adverse effect on survival; however, the geographical variation in survival observed for women diagnosed in 1987 was not apparent by 1993. We did not demonstrate a significant independent effect of surgical caseload on survival. We conclude that survival has increased partly as a consequence of screening and earlier diagnosis, but also due to improvements in the organisation and delivery of care.

Bone resorption predicts for skeletal complications in metastatic bone disease.

Relationships between the rate of bone resorption (measured by urinary N-telopeptide (Ntx) excretion) and a range of skeletal complications have been evaluated in patients with metastatic bone disease. A total of 121 patients had monthly measurements of Ntx during treatment with bisphosphonates. All skeletal-related events, plus hospital admissions for bone pain and death during the period of observation, were recorded. Data were available for 121 patients over the first 3-month period of monitoring (0-3 months) and 95 patients over the second 3-month period (4-6 months). N-telopeptide levels were correlated with the number of skeletal-related events and/or death (r=0.62, P<0.001 for 0-3 months and r=0.46, P<0.001 for 4-6 months, respectively). Patients with baseline Ntx values > or =100 nmol mmol(-1) creatinine (representing clearly accelerated bone resorption) were 19.48 times (95% CI 7.55, 50.22) more likely to experience a skeletal-related event/death during the first 3 months than those with Ntx <100 (P<0.001). In a multivariate logistic regression model, Ntx was highly predictive for events/death. This study is the first to indicate a strong correlation between the rate of bone resorption and the frequency of skeletal complications in metastatic bone disease. N-telopeptide appears useful in the prediction of patients most likely to experience skeletal complications and thus benefit from bisphosphonate treatment.

Lung cancer: the importance of seeing a respiratory physician.

Patients with lung cancer present to and are managed by a variety of clinicians. In this study the effect of involvement by a respiratory physician on the diagnosis, staging, treatment and survival of a large unselected group of lung cancer patients was investigated. The study population was derived from the Scottish Cancer Registry. A total of 3,855 patients diagnosed during 1995 with lung cancer were studied. The data were validated and supplemented by references to medical records. The study found that a respiratory physician had been involved in the initial management of 2,901 (75.3%) patients. These patients were found more likely to have had the cancer diagnosis confirmed by histological methods and to have received active treatment with surgery, radiotherapy or chemotherapy. Survival, 1 yr after diagnosis was higher in patients who saw a respiratory physician (24.4 versus 11.1%) and benefit was found to have remained 3 yrs after diagnosis (8.1 versus 3.7%). Although the patients who had not seen a respiratory physician were generally older, and had more extensive disease, after correcting for age, stage and other prognostic factors, the relative hazard ratio of death for those not managed by a respiratory physician was 1.44. The data from this study supports the recommendations of recent lung cancer guidelines for the early involvement by a respiratory physician.

Adjuvant ovarian ablation vs CMF chemotherapy in premenopausal breast cancer patients: trial update and impact of immunohistochemical assessment of ER status.

This trial, initiated in 1980, examined the relative values of adjuvant ovarian ablation and chemotherapy comprising cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in premenopausal women with pathological stage II breast cancer. With median follow-up for patients still alive of 13.9 years, there is no difference in survival between women receiving ovarian ablation and CMF (hazard ratio 1.01; 95% CI: 0.74, 1.37). Tumour oestrogen receptor (ER) status was assessed at the time using biochemical ligand-binding assay and retrospectively by immunohistochemistry (IHC). Agreement between these two methods was only fair, but both confirmed the importance of ER status in determining appropriate adjuvant systemic therapy. A statistically significant interaction between IHC quick score and treatment (P=0.001) showed ovarian ablation was more beneficial for patients with a positive quick score, whereas women with a quick score of 0 had a significantly higher risk of death with ovarian ablation (2.33; 95% CI: 1.30, 4.20). We have shown that IHC identifies women with ER 'poor' tumours for whom endocrine manipulation is not appropriate.

Variation in survival of women with breast cancer: Health Board remains a factor at 10 years.

Multivariate survival analysis of women with breast cancer diagnosed in 1987 with at least 10 years follow-up confirmed variations depending on the Health Board of their treatment. Differences in survival according to surgical caseload/specialization or deprivation were not statistically significant.

Prognostic factors in women with breast cancer: distribution by socioeconomic status and effect on differences in survival.

STUDY OBJECTIVE: To quantify and investigate differences in survival from breast cancer between women resident in affluent and deprived areas and define the contribution of underlying factors to this variation. DESIGN: Analysis of two datasets relating to breast cancer patients in Scotland: (1) population-based cancer registry data; (2) a subset of cancer registration records supplemented by abstraction of prognostic variables (stage, node status, tumour size, oestrogen receptor (ER) status, type of surgery, use of radiotherapy and use of adjuvant systemic therapy) from medical records. SETTING: Scotland. PATIENTS: (1) Cancer registration data on 21,751 women aged under 85 years diagnosed with primary breast cancer between 1978 and 1987; (2) national clinical audit data on 2035 women aged under 85 years diagnosed with primary breast cancer during 1987 for whom adequate medical records were available. MAIN RESULTS: Survival differences of 10% between affluent and deprived women were observed in both datasets, across all age groups. In the audit dataset, the distribution of ER status varied by deprivation group (65% ER positive in affluent group v 48% ER positive in deprived group; under 65 age group). Women aged under 65 with non-metastatic disease were more likely to have breast conservation than a mastectomy if they were affluent (45%) than deprived (32%); the affluent were more likely to receive endocrine therapy (65%) than the deprived (50%). However, these factors accounted for about 20% of the observed difference in survival between women resident in affluent and deprived areas. CONCLUSIONS: Deprived women with breast cancer have poorer outcomes than affluent women. This can only partly be explained by deprived women having more ER negative tumours than affluent women. Further research is required to identify other reasons for poorer outcomes in deprived women, with a view to reducing these survival differences.

Patterns of referral, management and survival of patients diagnosed with prostate cancer in Scotland during 1988 and 1993: results of a national, retrospective population-based audit.

OBJECTIVES: To examine patterns of referral, management and survival of men with prostate cancer, and to document changes over time. PATIENTS AND METHODS: All men registered with prostate cancer in 1988 and 1993 were identified from the Scottish Cancer Registry. Data were abstracted according to standard definitions from the available medical records of 930 men in 1988 and 1355 in 1993. RESULTS: There was limited evidence of multidisciplinary care, with only 8% of patients in 1988 being managed by both a urologist and a clinical oncologist within a year of diagnosis, increasing to 13% in 1993. Only a small proportion of patients were managed by clinical oncologists during the first year of care (14% in 1988 and 20% in 1993). Documentation of thorough staging information was poor, with a T stage being recorded in <30% of cases in both years. Documentation of metastatic status increased from 53% to 63% between 1988 and 1993, paralleling an increase in the use of bone scans. The proportion of cases with pathological grading obtained at diagnosis increased from 63% in 1988 to 68% by 1993. The use of PSA testing and core biopsies increased between the years while the use of transurethral prostatectomy decreased. More patients received radical radiotherapy within a year of diagnosis in 1993 than 1988, increasing from 6% to 9%, and more radical prostatectomies were also undertaken (0.2% to 2.3%). Nonetheless, most patients (81% in 1993) with no documented evidence of metastases received no active intervention (radical radiotherapy, radical prostatectomy, or 'watchful waiting'). The survival at 5 years increased nonsignificantly from 34% for the 1988 cohort to 38% for the 1993 cohort. CONCLUSION: This audit reveals considerable inconsistency in the management of men with prostate cancer in Scotland. Against a background of controversy about numerous aspects of the management of this disease, the need for a multidisciplinary approach, comprehensive staging and appropriate documentation is highlighted.

Management and survival of patients with lung cancer in Scotland diagnosed in 1995: results of a national population based study.

BACKGROUND: The prognosis of patients with lung cancer in Scotland is poor and not improving. This study was designed to document factors influencing referral, diagnostic evaluation, treatment, and survival in patients with lung cancer. METHODS: Patients diagnosed during 1995 were identified from the Scottish Cancer Registry and their medical records were reviewed. Adequate records were available in 91.2% of all potentially eligible cases. RESULTS: In 1995, patients in Scotland with lung cancer had a high rate of microscopic verification (74.1%) and 75.3% were assessed by a respiratory physician; however, only 56.8% received active treatment (resection 10.7%, radiotherapy 35.8%, chemotherapy 16.1%) and 2.9% participated in a clinical trial. Survival was poor with a median of 3.6 months; 21.1% (95% CI 19.8% to 22.4%) were alive at 1 year and 7.0% (95% CI 6.2% to 7.8%) at 3 years. Management by respiratory physician, oncologist, or thoracic surgeon was an independent predictor of access to potentially curative treatment and better survival. CONCLUSION: This national population based study demonstrates low use of treatment, poor survival, and the influence of process of care on survival. Implementation of evidence-based guidelines will require substantial changes in practice. Increasing the number of patients who receive treatment may improve survival.

Pre- and perinatal risk factors for childhood leukaemia and other malignancies: a Scottish case control study.

A case control study of Scottish children aimed to identify risk factors for leukaemia and other cancers operating in the prenatal environment, during delivery and neonatally. Cases (0-14 years) were age-and sex- matched to two population-based controls and details abstracted from the mother's hospital obstetric notes. Analyses of 144 leukaemias (124 acute lymphoblastic leukaemias (ALL)), 45 lymphomas, 75 central nervous system (CNS) tumours and 126 'other solid tumours' were conducted using conditional logistic regression. The presence of a neonatal infection significantly reduced the risk of ALL (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.95), particularly in 0- to 4-year-olds. Positive swab tests confirmed 47% of ALL cases with any infection and 46% of controls. This is consistent with the hypothesis that early exposure to infections may reduce the risk of childhood ALL. Asphyxia at birth significantly increased the risk of leukaemia, which was accounted for by ALL. For the 'other solid tumours' higher levels of maternal education were inversely associated with risk (OR 0.59, 95% CI 0.37-0.94) but positively associated with antibiotics (OR 2.16 95% CI 1.10-4.25) and respiratory tract infections (OR 14.1, 95% CI 1.76-113.7) in pregnancy. No obvious plausible patterns of risk were detected either within or across disease subgroups.

Breast cancer in Scotland: changes in treatment and work-load. Scottish Breast Cancer Focus Group and the Scottish Cancer Therapy Network.

Throughout Scotland, the patterns of care of patients with breast cancer were examined for the years 1987 and 1993. Substantial changes in oncological work-load were shown in the intervening period. The number of patients referred to an oncologist (clinical or medical) increased by 52% (from 1076 to 1634), the number of patients receiving postoperative radiotherapy to the breast or chest wall increased by 72% (from 724 to 1248) and the number of patients receiving adjuvant chemotherapy increased by 215% (from 123 to 388). The number of consultant oncologists increased by only 16% (from 32 to 37). If patients are to be treated to the standards expected, then increases in work-load must be matched by appropriate increases in staff.