Cancer risk in patients with fatigue

White, B. et al | Underlying cancer risk among patients with fatigue and other vague symptoms: a population-based cohort study in primary care | British Journal of General Practice February 2023; 73 (727): e75-e87. DOI: https://doi.org/10.3399/BJGP.2022.0371

Tiredness combined with other general symptoms like weight loss or abdominal pain could be a sign of cancer in older patients, according to a new study from University College London. Researchers looked at health records of over a quarter of a million people in England whose doctors noted that they were tired, but who didn’t have any ‘alarm’ symptoms of cancer. It showed that more than 3% of older patients who were tired and had other general symptoms were later diagnosed with cancer within the next 9 months. These findings could help doctors spot cancer in people who don’t have any obvious symptoms.

Full article: Underlying cancer risk among patients with fatigue and other vague symptoms: a population-based cohort study in primary care

Managing NHS backlogs and waiting times in England

This report on backlogs for elective and cancer care examines the design of NHS England’s recovery plan, how the NHS has been implementing the plan and the ongoing risks NHSE has to manage | National Audit Office

According to this report, the plan to reduce long waits for NHS elective and cancer care services by 2025 is at serious risk. It finds that the funding government allocated for recovering services has not kept pace with inflation, and the NHS faces workforce and productivity issues.

Under the recovery plan, the NHS expects GPs to avoid referring some kinds of patients whom they would traditionally have referred for elective care. Instead, GPs will be able to obtain advice and guidance for such patients from hospital specialists and then manage the patients within the primary care system.

The advice and guidance initiative might shift work from hospitals to GPs, but the GP workforce is under pressure too. The fully-qualified permanent GP workforce decreased by 4% between June 2017 and June 2022. It is unclear whether GPs will be able to manage the additional workload that might result and whether databases across the country are capable of sharing and updating patient information efficiently to support this. NHS England is monitoring the impact on both the primary and secondary care workforces.

Full report: Managing NHS backlogs and waiting times in England

Report summary: Managing NHS backlogs and waiting times in England

Press release: Managing NHS backlogs and waiting times in England

NHS gives GP teams direct access to tests to speed up cancer diagnosis

Tens of thousands of cancers could be detected sooner each year thanks to a national roll out of fast-track testing | via NHS England

NHS England is expanding direct access to diagnostic scans across all GP practices, helping cut waiting times and speeding up a cancer diagnosis or all-clear for patients. From this month, every GP team will start to be able to directly order CT scans, ultrasounds or brain MRIs for patients with concerning symptoms, but who fall outside the NICE guideline threshold for an urgent suspected cancer referral.

The scheme will allow GPs to order these checks directly, helping to cut down wait times to as little as four weeks. Hundreds of thousands of initial hospital appointments could also be freed up under the approach by reducing the need for a specialist consultation first – boosting efforts to address the Covid backlog.

Urgent cancer referrals have been at record levels since March 2021, with over a quarter of a million people (255,055) checked following an urgent GP referral in August – the highest number since records began.

Full detail: NHS gives GP teams direct access to tests to speed up cancer diagnosis

See also: Direct access to diagnostics will reassure patients – but GP workforce must be increased and given appropriate training and support | Royal College of General Practitioners

Primary care practice and cancer suspicion during the first three COVID-19 lockdowns in the UK: a qualitative study

British Journal of General Practice | Vol. 72, Issue 723

Study (17 interviews) notes some of changes will have been a positive step forward in modernisation of practice, but net impact of pandemic on detection of cancer has been negative, the full effect on stage, treatment intent, & survival may not be fully understood for some time.

Background The COVID-19 pandemic has profoundly affected UK primary care, and as a result the route to cancer diagnosis for many patients.

Aim To explore how the pandemic affected primary care practice, in particular cancer suspicion, referral, and diagnosis, and how this experience evolved as the pandemic progressed.

Design and setting Seventeen qualitative interviews were carried out remotely with primary care staff.

Method Staff from practices in England that expressed an interest in trialling an electronic safety-netting tool were invited to participate. Remote, semi-structured interviews were conducted from September 2020 to March 2021. Data analysis followed a thematic analysis and mind-mapping approach.

Results The first lockdown was described as providing time to make adjustments to allow remote and minimal-contact consultations but caused concerns over undetected cancers. These concerns were realised in summer and autumn 2020 as the participants began to see higher rates of late-stage cancer presentation. During the second and third lockdowns patients seemed more willing to consult. This combined with usual winter pressures, demands of the vaccine programme, and surging levels of COVID-19 meant that the third lockdown was the most difficult. New ways of working were seen as positive when they streamlined services but also unsafe if they prevented GPs from accessing all relevant information and resulted in delayed cancer diagnoses.

Conclusion The post-pandemic recovery of cancer care is dependent on the recovery of primary care. The COVID-19 pandemic has highlighted and exacerbated vulnerabilities in primary care but has also provided new ways of working that may help the recovery.

Full article – Primary care practice and cancer suspicion during the first three COVID-19 lockdowns in the UK: a qualitative study | Claire Friedemann Smith, Brian D Nicholson, Yasemin Hirst, Susannah Fleming, Clare R Bankhead; British Journal of General Practice 2022; 72 (723)

High street pharmacies spot cancers in new NHS early diagnosis drive

Staff in high street pharmacies will be funded to spot signs of cancer as part of a new drive to catch tumours early when they are easier to treat | NHS England

The NHS Long Term Plan committed to increasing the proportion of cancers caught early, when they are easier to treat, from half to three in four. The community pharmacy pilot, to be carried out in areas across the country, will see staff spot signs of cancer in people who might not have noticed symptoms. Those with symptoms including a cough that lasts for three weeks or more, difficulty swallowing or blood in their urine will be referred direct for scans and checks without needing to see a GP if staff think it could be cancer.

Full detail: High street pharmacies spot cancers in new NHS early diagnosis drive

See also: Pilot scheme will allow pharmacists to refer potential cancer cases directly to hospital | BMJ

Government’s new 10-year cancer plan will incorporate lessons learned during the pandemic

Cancer organisations and specialists are being asked to contribute suggestions on how the NHS in England can improve diagnosis and treatment of the disease | via guidelines.co.uk

The Secretary of State for Health and Social Care, Sajid Javid, has appealed for evidence to inform a new 10-year cancer plan expected this summer. The ambition is to incorporate innovations brought about by the COVID-19 pandemic, and identify other ideas for improving cancer services.

In building on the NHS long term plan, Mr Javid said that he wanted to:

• increase the number of early-stage cancer diagnoses, including by intensifying research on new early diagnostic tools
• boost the oncology workforce in the NHS
• tackle disparities and inequalities in access to care and time to treatment
• intensify research on mRNA vaccines and therapeutics for cancer by supporting industry to develop new cancer treatments that combine expertise in cancer immunotherapy and vaccine capabilities developed during the pandemic
• improve cancer prevention by tackling major risk factors.

The call for evidence will run for 8 weeks, and is open to any organisation, as well as individuals aged 16 years and over.

Full detail: Government’s new 10-year cancer plan will incorporate lessons learned during the pandemic

See also: 10 Year Cancer Plan: Call for Evidence | Department of Health & Social Care

Factors affecting the decision to investigate older adults with potential cancer symptoms

British Journal of General Practice 2022; 72 (714): e1-e10.| DOI: https://doi.org/10.3399/BJGP.2021.0257

Older age and frailty increase the risk of morbidity and mortality from cancer surgery and intolerance of chemotherapy and radiotherapy. The effect of old age on diagnostic intervals is unknown; however, older adults need a balanced approach to the diagnosis and management of cancer symptoms, considering the benefits of early diagnosis, patient preferences, and the likely prognosis of a cancer.

The aim of this systematic review was to examine the association between older age and diagnostic processes for cancer, and the specific factors that affect diagnosis.

Thematic synthesis highlighted three important factors that resulted in uncertainty in decisions involving older adults: presence of frailty, comorbidities, and cognitive impairment. Data suggested patients wished to be involved in decision making, but the presence of cognitive impairment and the need for additional time within a consultation were significant barriers.

This review has highlighted uncertainty in the management of older adults with cancer symptoms. Patients and their family wished to be involved in these decisions. Given the uncertainty regarding optimum management of this group of patients, a shared decision-making approach is important.

Full paper: Factors affecting the decision to investigate older adults with potential cancer symptoms: a systematic review

Personal use of permanent hair dyes and cancer risk and mortality in US women: prospective cohort study

Objective To evaluate the associations between personal use of permanent hair dyes and cancer risk and mortality.

Design Prospective cohort study.

Setting and participants 117 200 women enrolled in the Nurses’ Health Study, an ongoing prospective cohort study of female nurses in the United States. The women were free of cancer at baseline, reported information on personal use of permanent hair dyes, and were followed for 36 years.

Exposure Status, duration, frequency, and integral use (cumulative dose calculated from duration and frequency) of permanent hair dyes. Age at first use and time since first use of permanent hair dyes.

Main outcome measures Associations of personal use of permanent hair dyes with risk of overall cancer and specific cancers, and cancer related death. Age and multivariable adjusted hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazard models.

Results Ever users of permanent hair dyes had no significant increases in risk of solid cancers (n=20 805, excluding non-melanoma skin cancers; hazard ratio 0.98, 95% confidence interval 0.96 to 1.01) or hematopoietic cancers overall (n=1807; 1.00, 0.91 to 1.10) compared with non-users. Additionally, ever users did not have an increased risk of most specific cancers (cutaneous squamous cell carcinoma, bladder cancer, melanoma, estrogen receptor positive breast cancer, progesterone receptor positive breast cancer, hormone receptor positive breast cancer, brain cancer, colorectal cancer, kidney cancer, lung cancer, and most of the major subclasses and histological subtypes of hematopoietic cancer) or cancer related death (n=4860; 0.96, 0.91 to 1.02). Basal cell carcinoma risk was slightly increased for ever users (n=22 560; 1.05, 1.02 to 1.08). Cumulative dose was positively associated with risk of estrogen receptor negative breast cancer, progesterone receptor negative breast cancer, hormone receptor negative breast cancer, and ovarian cancer. An increased risk of Hodgkin lymphoma was observed only for women with naturally dark hair (based on 70 women, 24 with dark hair), and a higher risk of basal cell carcinoma was observed for women with naturally light hair.

Conclusion No positive association was found between personal use of permanent hair dye and risk of most cancers and cancer related mortality. The increased risk of basal cell carcinoma, breast cancer (estrogen receptor negative, progesterone receptor negative, hormone receptor negative) and ovarian cancer, and the mixed findings in analyses stratified by natural hair color warrant further investigation.

Reference: BMJ 2020;370:m2942

Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study

Objective To quantify the predictive value of unexpected weight loss (WL) for cancer according to patient’s age, sex, smoking status, and concurrent clinical features (symptoms, signs, and abnormal blood test results).

Design Diagnostic accuracy study.

Setting Clinical Practice Research Datalink electronic health records data linked to the National Cancer Registration and Analysis Service in primary care, England.

Participants 63 973 adults (≥18 years) with a code for unexpected WL from 1 January 2000 to 31 December 2012.

Main outcome measures Cancer diagnosis in the six months after the earliest weight loss code (index date). Codes for additional clinical features were identified in the three months before to one month after the index date. Diagnostic accuracy measures included positive and negative likelihood ratios, positive predictive values, and diagnostic odds ratios.

Results Of 63 973 adults with unexpected WL, 37 215 (58.2%) were women, 33 167 (51.8%) were aged 60 years or older, and 16 793 (26.3%) were ever smokers. 908 (1.4%) had a diagnosis of cancer within six months of the index date, of whom 882 (97.1%) were aged 50 years or older. The positive predictive value for cancer was above the 3% threshold recommended by the National Institute for Health and Care Excellence for urgent investigation in male ever smokers aged 50 years or older, but not in women at any age. 10 additional clinical features were associated with cancer in men with unexpected WL, and 11 in women. Positive likelihood ratios in men ranged from 1.86 (95% confidence interval 1.32 to 2.62) for non-cardiac chest pain to 6.10 (3.44 to 10.79) for abdominal mass, and in women from 1.62 (1.15 to 2.29) for back pain to 20.9 (10.7 to 40.9) for jaundice. Abnormal blood test results associated with cancer included low albumin levels (4.67, 4.14 to 5.27) and raised values for platelets (4.57, 3.88 to 5.38), calcium (4.28, 3.05 to 6.02), total white cell count (3.76, 3.30 to 4.28), and C reactive protein (3.59, 3.31 to 3.89). However, no normal blood test result in isolation ruled out cancer. Clinical features co-occurring with unexpected WL were associated with multiple cancer sites.

Conclusion The risk of cancer in adults with unexpected WL presenting to primary care is 2% or less and does not merit investigation under current UK guidelines. However, in male ever smokers aged 50 years or older and in patients with concurrent clinical features, the risk of cancer warrants referral for invasive investigation. Clinical features typically associated with specific cancer sites are markers of several cancer types when they occur with unexpected WL.

Reference: BMJ 2020;370:m2651

Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study

Background

Lynch syndrome is associated with an increased risk of colorectal cancer and with a broader spectrum of cancers, especially endometrial cancer. In 2011, our group reported long-term cancer outcomes (mean follow-up 55·7 months [SD 31·4]) for participants with Lynch syndrome enrolled into a randomised trial of daily aspirin versus placebo. This report completes the planned 10-year follow-up to allow a longer-term assessment of the effect of taking regular aspirin in this high-risk population.

Methods

In the double-blind, randomised CAPP2 trial, 861 patients from 43 international centres worldwide (707 [82%] from Europe, 112 [13%] from Australasia, 38 [4%] from Africa, and four [<1%] from The Americas) with Lynch syndrome were randomly assigned to receive 600 mg aspirin daily or placebo. Cancer outcomes were monitored for at least 10 years from recruitment with English, Finnish, and Welsh participants being monitored for up to 20 years. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. The trial is registered with the ISRCTN registry, number ISRCTN59521990.

Findings

Between January, 1999, and March, 2005, 937 eligible patients with Lynch syndrome, mean age 45 years, commenced treatment, of whom 861 agreed to be randomly assigned to the aspirin group or placebo; 427 (50%) participants received aspirin and 434 (50%) placebo. Participants were followed for a mean of 10 years approximating 8500 person-years. 40 (9%) of 427 participants who received aspirin developed colorectal cancer compared with 58 (13%) of 434 who received placebo. Intention-to-treat Cox proportional hazards analysis revealed a significantly reduced hazard ratio (HR) of 0·65 (95% CI 0·43–0·97; p=0·035) for aspirin versus placebo. Negative binomial regression to account for multiple primary events gave an incidence rate ratio of 0·58 (0·39–0·87; p=0·0085). Per-protocol analyses restricted to 509 who achieved 2 years’ intervention gave an HR of 0·56 (0·34–0·91; p=0·019) and an incidence rate ratio of 0·50 (0·31–0·82; p=0·0057). Non-colorectal Lynch syndrome cancers were reported in 36 participants who received aspirin and 36 participants who received placebo. Intention-to-treat and per-protocol analyses showed no effect. For all Lynch syndrome cancers combined, the intention-to-treat analysis did not reach significance but per-protocol analysis showed significantly reduced overall risk for the aspirin group (HR=0·63, 0·43–0·92; p=0·018). Adverse events during the intervention phase between aspirin and placebo groups were similar, and no significant difference in compliance between intervention groups was observed for participants with complete intervention phase data; details reported previously.

Interpretation

The case for prevention of colorectal cancer with aspirin in Lynch syndrome is supported by our results.

Funding

Cancer Research UK, European Union, MRC, NIHR, Bayer Pharma AG, Barbour Foundation.

Reference: The Lancet, VOLUME 395, ISSUE 10240, P1855-1863, JUNE 13, 2020