Inequalities in the recovery of colorectal cancer services during the COVID-19 pandemic: a national population-based study.

AIM: Evidence is lacking on whether there were inequalities in the recovery of colorectal cancer (CRC) services within the English National Health Service (NHS) following the COVID-19 pandemic. The aim of this study was to evaluate recovery according to patient age and socioeconomic status. METHOD: Using routinely collected data, CRC patients diagnosed and treated in the English NHS were identified for two timeframes: the 'initial pandemic period' (April-June 2020) and the 'pandemic period' (April 2020-March 2022). Poisson models evaluated changes in numbers of diagnoses, major resections, adjuvant chemotherapy and neoadjuvant radiotherapy use for each timeframe, relative to the equivalent pre-pandemic timeframe (April-June 2019 and April 2018-March 2020, respectively), stratified by age and socioeconomic status. Tumour stage at presentation was evaluated over time. RESULTS: Substantial deficits in diagnoses, major resections and adjuvant chemotherapy were identified in the initial pandemic period, whilst the use of neoadjuvant radiotherapy increased. Overall, these deficits recovered. Patients outside screening age, and in the most deprived group, had greater deficits in diagnoses and major resections. There was no evidence of stage migration by June 2021. CONCLUSIONS: CRC services showed recovery to baseline during the pandemic. However, evident inequalities must be addressed in ongoing recovery efforts. Long-term outcomes will fully establish the impact of the pandemic on CRC patients.

Impact of patient choice and hospital competition on patient outcomes after rectal cancer surgery: A national population-based study.

BACKGROUND: The objective of the current national cohort study was to analyze the correlation between choice and competition on outcomes after cancer surgery in rectal cancer. METHODS: The analysis included all men who underwent rectal cancer surgery in the English National Health Service between March 2015 and April 2019 (n = 13,996). Multilevel logistic regression was used to assess the effect of a rectal cancer surgery center being located in a competitive environment (based on the number of centers within a threshold distance) and being a successful competitor (based on the ability to attract patients from other hospitals) on eight patient-level outcomes: 30- and 90-day emergency readmissions, 30-day re-operation rates, 90-day postoperative mortality, length of stay >14 days, circumferential resection margin status, rates of primary procedure with a permanent stoma, and rates of persistent stoma 18 months after anterior resection. RESULTS: With adjustment for patient characteristics, patients who underwent surgery in centers located in a stronger competitive environment were less likely to have an abdominoperineal excision or a Hartman's procedure (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.55-0.97, p = .04). Additionally, individuals who received treatment at hospitals that were successful competitors had a lower risk of a 90-day readmission following rectal cancer surgery (OR, 0.86; 95% CI, 0.76-0.97, p = .03) and were less likely to have a persistent stoma at 18 months after anterior resection (OR, 0.75; 95% CI, 0.61-0.93, p = .02). CONCLUSIONS: Hospitals located in areas of high competition are associated with better patient outcomes and improved processes of care for rectal cancer surgery.

What is the impact of hospital and surgeon volumes on outcomes in rectal cancer surgery?

AIM: Evidence for a positive volume-outcome relationship for rectal cancer surgery is unclear. This study aims to evaluate the volume-outcome relationship for rectal cancer surgery at hospital and surgeon level in the English National Health Service (NHS). METHOD: All patients undergoing a rectal cancer resection in the English NHS between 2015 and 2019 were included. Multilevel multivariable logistic regression was used to model relationships between outcomes and mean annual hospital and surgeon volumes (using a linear plus a quadratic term for volume) with adjustment for patient characteristics. RESULTS: A total of 13 858 patients treated in 166 hospitals were included. Six hospitals (3.6%) performed fewer than 10 rectal cancer resections per year, and 381 surgeons (45.0%) performed fewer than five such resections per year. Patients treated by high-volume surgeons had a reduced length of stay (p = 0.016). No statistically significant volume-outcome relationships were demonstrated for 90-day mortality, 30-day unplanned readmission, unplanned return to theatre, stoma at 18 months following anterior resection, positive circumferential resection margin and 2-year all-cause mortality at either hospital or surgeon level (p values > 0.05). CONCLUSION: Almost half of colorectal surgeons in England do not meet national guidelines for rectal cancer surgeons to perform a minimum of five major resections annually. However, our results suggest that centralizing rectal cancer surgery with the main focus of increasing operative volume may have limited impact on NHS surgical outcomes. Therefore, quality improvement initiatives should address a wider range of evidence-based process measures, across the multidisciplinary care pathway, to enhance outcomes for patients with rectal cancer.

Survival outcomes associated with completion of adjuvant oxaliplatin-based chemotherapy for stage III colon cancer: A national population-based study.

The impact of cycle completion rates of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer in real-world practice is unknown. We assessed its impact, and that of treatment modification, on 3-year cancer-specific mortality. Four thousand one hundred and forty-seven patients with pathological stage III colon cancer undergoing major resection from 2014 to 2017 in the English National Health Service were included. Chemotherapy data came from linked national administrative datasets. Competing risk regression analysis for 3-year cancer-specific mortality was performed according to completion of <6, 6-11, or 12 5-fluoropyrimidine and oxaliplatin (FOLFOX) cycles, or <4, 4-7, or 8 capecitabine and oxaliplatin (CAPOX) cycles, adjusted for patient, tumour and hospital-level characteristics. Median age was 64 years. Thirty-two per cent of patients had at least one comorbidity. Forty-two per cent of patients had T4 disease, and 40% had N2 disease. Compared to completion of 12 FOLFOX cycles, cancer-specific mortality was higher in patients completing <6 cycles [subdistribution hazard ratios (sHR) 2.17; 95% CI 1.56-3.03] or 6-11 cycles (sHR 1.40; 95% CI 1.09-1.78) (P < .001). Compared to completion of 8 CAPOX cycles, cancer-specific mortality was higher in patients completing <4 cycles (sHR 2.02; 95% CI 1.53-2.67) or 4-7 cycles (sHR 1.63; 95% CI 1.27-2.10) (P < .001). Dose reduction and early oxaliplatin discontinuation did not impact mortality in patients completing all cycles. Completion of all cycles of chemotherapy was associated with improved cancer-specific survival in real-world practice. Poor prognostic factors may have affected findings, however, patients completing <50% of cycles had poor outcomes. Clinicians may wish to facilitate completion with treatment modification in those able to tolerate it.

Outcomes of colorectal cancer resection in patients with inflammatory bowel disease: a national population-based analysis in England and Wales.

AIM: The aim was to compare early postoperative outcomes and 2-year cancer-specific mortality following colorectal cancer (CRC) resection in patients with and without inflammatory bowel disease (IBD) in England and Wales. METHOD: Records for patients in the National Bowel Cancer Audit who had major CRC resection between April 2014 and December 2017 were linked to routinely collected hospital level administrative datasets and chemotherapy and radiotherapy datasets. Multivariable regression models were used to compare outcomes with adjustment for patient and tumour characteristics. RESULTS: In all, 63 365 patients were included. 1285 (2.0%) had an IBD diagnosis: 839 (65.3%) ulcerative colitis, 435 (33.9%) Crohn's disease and 11 (0.9%) were indeterminate. IBD patients were younger, had more advanced cancer staging and a higher proportion of right-sided tumours. They also had a higher proportion of emergency resection, total/subtotal colectomy, open surgery and stoma formation at resection, with longer hospital admissions and higher rates of unplanned readmission and reoperation. Fewer rectal cancer patients with IBD received neoadjuvant radiotherapy (24.8% vs. 36.0%, P = 0.005) whilst similar proportions of Stage III colon cancer patients received adjuvant chemotherapy. Ninety-day postoperative mortality was similar, but unadjusted 2-year cancer-specific mortality was significantly higher in patients with IBD (subdistribution hazard ratio 1.35, 95% CI 1.18-1.55). Risk adjustment for patient and tumour factors reduced this association (adjusted subdistribution hazard ratio 1.22, 95% CI 1.05-1.43). CONCLUSION: Patients with IBD and CRC are a distinct patient group who develop CRC at a younger age and undergo more radical surgery. They have worse cancer survival, with the difference in prognosis appearing after the early postoperative period.

Frailty in Older Patients Undergoing Emergency Laparotomy: Results From the UK Observational Emergency Laparotomy and Frailty (ELF) Study.

OBJECTIVE: This study aimed to document the prevalence of frailty in older adults undergoing emergency laparotomy and to explore relationships between frailty and postoperative morbidity and mortality. SUMMARY BACKGROUND DATA: The majority of adults undergoing emergency laparotomy are older adults (≥65 y) that carry the highest mortality. Improved understanding is urgently needed to allow development of targeted interventions. METHODS: An observational multicenter (n=49) UK study was performed (March-June 2017). All older adults undergoing emergency laparotomy were included. Preoperative frailty score was calculated using the progressive Clinical Frailty Score (CFS): 1 (very fit) to 7 (severely frail). Primary outcome measures were the prevalence of frailty (CFS 5-7) and its association to mortality at 90 days postoperative. Secondary outcomes included 30-day mortality and morbidity, length of critical care, and overall hospital stay. RESULTS: A total of 937 older adults underwent emergency laparotomy: frailty was present in 20%. Ninety-day mortality was 19.5%. After age and sex adjustment, the risk of 90-day mortality was directly associated with frailty: CFS 5 adjusted odds ratio (aOR) 3.18 [95% confidence interval (CI), 1.24-8.14] and CFS 6/7 aOR 6·10 (95% CI, 2.26-16.45) compared with CFS 1. Similar associations were found for 30-day mortality. Increasing frailty was also associated with increased risk of complications, length of Intensive Care Unit, and overall hospital stay. CONCLUSIONS: A fifth of older adults undergoing emergency laparotomy are frail. The presence of frailty is associated with greater risks of postoperative mortality and morbidity and is independent of age. Frailty scoring should be integrated into acute surgical assessment practice to aid decision-making and development of novel postoperative strategies.

The impact of the first peak of the COVID-19 pandemic on colorectal cancer services in England and Wales: A national survey.

AIM: The object of this work was to study how National Health Service hospitals in England and Wales aimed to maintain effective and safe colorectal cancer (CRC) services during the first peak of the COVID-19 pandemic (April 2020). METHOD: A national survey was performed among all 148 hospitals providing CRC services. Information was collected about changes in referrals, diagnostic, staging and therapeutic procedures, as well as whether there was access to a 'cold site' (a hospital facility free of COVID-19). Clinicians in each hospital were also asked to give the 'single most important lesson learned' about keeping services safe and effective. RESULTS: Full responses were received from 123 (83%) hospitals, and information about 'cold sites' was available for 146 (99%). Eighty hospitals (54%) had access to a 'cold site' and this was increased in regions with higher COVID-19 infection rates (p <0.001). Of the 123 responding hospitals, 105 (85%) indicated that referrals of patients with suspected CRC had dropped by at least 30%, and 69 (56%) indicated that treatment plans were altered in at least 50% of CRC patients. However, 'cold site' availability protected the capacity for diagnostic colonoscopy (p = 0.013) and CRC resection (p = 0.010). Many 'lessons learned' highlighted the importance of adequate structural service organization, often mentioning 'cold sites' and regional coordination as examples, good communication and triage of patients based on clinical urgency. CONCLUSION: Access to 'cold sites', as well as regional coordination, clear communication and strong leadership, were found to be pivotal in maintaining capacity for diagnosis and treatment of CRC during the COVID-19 surge.

Improving risk models for patients having emergency bowel cancer surgery using linked electronic health records: a national cohort study.

BACKGROUND: Life-saving emergency major resection of colorectal cancer (CRC) is a high-risk procedure. Accurate prediction of postoperative mortality for patients undergoing this procedure is essential for both healthcare performance monitoring and preoperative risk assessment. Risk-adjustment models for CRC patients often include patient and tumour characteristics, widely available in cancer registries and audits. The authors investigated to what extent inclusion of additional physiological and surgical measures, available through linkage or additional data collection, improves accuracy of risk models. METHODS: Linked, routinely-collected data on patients undergoing emergency CRC surgery in England between December 2016 and November 2019 were used to develop a risk model for 90-day mortality. Backwards selection identified a 'selected model' of physiological and surgical measures in addition to patient and tumour characteristics. Model performance was assessed compared to a 'basic model' including only patient and tumour characteristics. Missing data was multiply imputed. RESULTS: Eight hundred forty-six of 10 578 (8.0%) patients died within 90 days of surgery. The selected model included seven preoperative physiological and surgical measures (pulse rate, systolic blood pressure, breathlessness, sodium, urea, albumin, and predicted peritoneal soiling), in addition to the 10 patient and tumour characteristics in the basic model (calendar year of surgery, age, sex, ASA grade, TNM T stage, TNM N stage, TNM M stage, cancer site, number of comorbidities, and emergency admission). The selected model had considerably better discrimination compared to the basic model (C-statistic: 0.824 versus 0.783, respectively). CONCLUSION: Linkage of disease-specific and treatment-specific datasets allowed the inclusion of physiological and surgical measures in a risk model alongside patient and tumour characteristics, which improves the accuracy of the prediction of the mortality risk for CRC patients having emergency surgery. This improvement will allow more accurate performance monitoring of healthcare providers and enhance clinical care planning.

Measuring variation in the quality of systemic anti-cancer therapy delivery across hospitals: A national population-based evaluation.

AIM: To date, there has been little systematic assessment of the quality of care associated with systemic anti-cancer therapy (SACT) delivery across national healthcare systems. We evaluated hospital-level toxicity rates during SACT treatment as a means of identifying variation in care quality. METHODS: All colorectal cancer (CRC) patients receiving SACT within 106 English National Health Service (NHS) hospitals between 2016 and 2019 were included. Severe acute toxicity rates were derived from hospital administrative data using a validated coding framework. Variation in hospital-level toxicity rates was assessed separately in the adjuvant and metastatic settings. Toxicity rates were adjusted for age, sex, comorbidity, performance status, tumour site, and TNM staging. RESULTS: Eight thousand one hundred and seventy three patients received SACT in the adjuvant setting, and 7,683 patients in the metastatic setting. Adjusted severe acute toxicity rates varied between hospitals from 11% to 49% for the adjuvant cohort, and from 25% to 67% for the metastatic cohort. Compared to the national mean toxicity rate in the adjuvant cohort, six hospitals were more than two standard deviations (2SD) above, and four hospitals were more than 2SD below. In the metastatic cohort, six hospitals were more than 2SD above, and seven hospitals were more than 2SD below the national mean toxicity rate. Overall, 12 hospitals (12%) had toxicity rates more than 2SD above the national mean, and 11 (10%) had rates more than 2SD below. CONCLUSION: There is substantial variation in hospital-level severe acute toxicity rates in both the adjuvant and metastatic settings, despite risk-adjustment. Ongoing reporting of this performance indicator can be used to focus further investigation of toxicity rates and stimulate quality improvement initiatives to improve care.

Determinants of variation in radical local treatment for men with high-risk localised or locally advanced prostate cancer in England.

BACKGROUND: Many factors are implicated in the potential 'under-treatment' of prostate cancer but little is known about the between-hospital variation. METHODS: The National Prostate Cancer Audit (NPCA) database was used to identify high-risk localised or locally advanced prostate cancer patients in England, between January 2014 and December 2017, and the treatments received. Hospital-level variation in radical local treatment was explored visually using funnel plots. The intra-class correlation coefficient (ICC) quantified the between-hospital variation in a random-intercept multivariable logistic regression model. RESULTS: 53,888 men, from 128 hospitals, were included and 35,034 (65.0%) received radical local treatment. The likelihood of receiving radical local treatment was increased in men who were younger (the strongest predictor), more affluent, those with fewer comorbidities, and in those with a non-Black ethnic background. There was more between-hospital variation (P < 0.001) for patients aged ≥80 years (ICC: 0.235) compared to patients aged 75-79 years (ICC: 0.070), 70-74 years (ICC: 0.041), and <70 years (ICC: 0.048). Comorbidity and socioeconomic deprivation did not influence the between-hospital variation. CONCLUSIONS: Radical local treatment of high-risk localised or locally advanced prostate cancer depended strongly on age and comorbidity, but also on socioeconomic deprivation and ethnicity, with the between-hospital variation being highest in older patients.

Development and validation of a coding framework to identify severe acute toxicity from systemic anti-cancer therapy using hospital administrative data.

BACKGROUND: The capture of toxicities from systemic anti-cancer therapy (SACT) in real-world data will complement results from clinical trials. The aim of this study was to develop and validate a comprehensive coding framework to identify severe acute toxicity in hospital administrative data. METHODS: A coding framework was developed to identify diagnostic codes representing severe acute toxicity in hospital administrative data. The coding framework was validated on a sample of 23,265 colon cancer patients treated in the English National Health Service between 1 June 2014 and 31 December 2017. This involved comparing individual toxicities according to the receipt of SACT and according to different SACT regimens, as well as assessing the associations of predictive factors and outcomes with toxicity. RESULTS: The severe acute toxicities captured by the developed coding framework were shown to vary across clinical groups with an overall rate of 26.4% in the adjuvant cohort, 53.4% in the metastatic cohort, and 12.5% in the comparison group receiving no chemotherapy. Results were in line with regimen-specific findings from clinical trials. For example, patients receiving additional bevacizumab had higher rates of bleeding (12.5% vs. 2.7%), gastrointestinal perforation (5.6% vs. 2.9%) and fistulation (1.4% vs. 0.5%), and allergic drug reactions (1.4% vs. 0.5%). Severe acute toxicity was associated with pre-existing renal (p = 0.001) and cardiac disease (p = 0.038), and urgency of surgery (p = 0.004). Severe toxicity also predicted lower rates of completion of chemotherapy (p = <0.001) and an increased likelihood of altered administration route (p = <0.001). CONCLUSION: These results demonstrate that the developed coding framework captures severe acute toxicities from hospital administrative data of colon cancer patients. A similar approach can be used for patients with other cancer types, receiving different regimens. Toxicity captured in administrative data can be used to compare treatment outcomes, inform clinical decision making, and provide opportunities for benchmarking and provider performance monitoring.

Surgical Treatment and Outcomes of Colorectal Cancer Patients During the COVID-19 Pandemic: A National Population-based Study in England.

To compare the management and outcomes of colorectal cancer (CRC) patients during the first 2 months of the COVID-19 pandemic with the preceding 6 months. BACKGROUND: The pandemic has affected the diagnosis and treatment of CRC patients worldwide. Little is known about the safety of major resection and whether creating "cold" sites (COVID-free hospitals) is effective. METHODS: A national study in England used administrative hospital data for 14,930 CRC patients undergoing surgery between October 1, 2019, and May 31, 2020. Mortality of CRC resection was compared before and after March 23, 2020 ("lockdown" start). RESULTS: The number of elective CRC procedures dropped sharply during the pandemic (from average 386 to 214 per week), whereas emergency procedures were hardly affected (from 88 to 84 per week). There was little change in characteristics of surgical patients during the pandemic. Laparoscopic surgery decreased from 62.5% to 35.9% for elective and from 17.7% to 9.7% for emergency resections. Surgical mortality increased slightly (from 0.9% to 1.2%, P = 0.06) after elective and markedly (from 5.6% to 8.9%, P = 0.003) after emergency resections. The observed increase in mortality during the first phase of the pandemic was similar in "cold" and "hot" sites (P > 0.5 elective and emergency procedures). CONCLUSIONS: The pandemic resulted in a 50% reduction in elective CRC procedures during the initial surge and a substantial increase in mortality after emergency resection. There was no evidence that surgery in COVID-free "cold" sites led to better outcomes in the first 2 months.

Validity of chemotherapy information derived from routinely collected healthcare data: A national cohort study of colon cancer patients.

BACKGROUND: We used a structured approach to validate chemotherapy information derived from a national routinely collected chemotherapy dataset and from national administrative hospital data. METHODS: 10,280 patients who had surgical resection with stage III colon cancer were included. First, we compared information derived from the national chemotherapy dataset (SACT) and from the administrative hospital dataset (HES) in the English NHS with respect to receipt of adjuvant chemotherapy (ACT). Second, we compared regimen and number of cycles in linked patient-level records. Third, we carried out a sensitivity analysis to establish to what extent the impact of ACT receipt differed according to data source. RESULTS: 6,012 patients (58 %) received ACT according to either dataset. Of these patients, 3,460 (58 %) had ACT records in both datasets, 1,649 (27 %) in SACT alone, and 903 (15 %) in HES alone. Of the 3,460 patients with records in both datasets, 3,320 (96 %) had matching regimens. There was good agreement on cycle number with similar proportions of patients recorded with a single cycle (6 % in SACT vs. 7 % in HES) and slightly fewer patients recorded with more than 8 cycles in SACT (32 % in SACT vs. 35 % in HES). 3-year cancer-specific mortality was similar for patients receiving ACT, regardless of whether a patient received ACT according to SACT alone (16.6 %), according to HES alone (16.8 %), or according to either SACT or HES (17.1 %). CONCLUSION: Routinely collected national chemotherapy data and administrative hospital data are highly accurate in recording regimen and number of chemotherapy cycles. However, chemotherapy information should ideally be captured from both datasets to avoid under-capture, particularly of oral chemotherapy from administrative hospital data, and to minimise bias.

Real-world outcomes associated with new cancer medicines approved by the Food and Drug Administration and European Medicines Agency: A retrospective cohort study.

PURPOSE: Real-World Data (RWD) studies are increasingly used to support regulatory approvals, reimbursement decisions, and changes in clinical practice for novel cancer drugs. However, few studies have systematically appraised their quality or compared outcomes to pivotal trials. METHODS: All RWD studies (2010-2019) for drugs approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) from 2010 to 2015 for solid organ tumours in the non-curative setting were identified. Quality assessment was undertaken using the Newcastle Ottawa Scale. Survival differences between each RWD study and the pivotal trial were determined using a related sample Wilcoxon signed-rank test. RESULTS: 293 RWD studies for 45 of the 57 drug indications approved by the FDA/EMA were identified. The most common tumour types were prostate cancer (29%, n = 86) and melanoma (15%, n = 43). A quarter of the studies had industry funding. No high-quality studies were identified, and 78% were low quality. Comparative survival analysis between RWD and pivotal trials was possible for 224 studies (37 drug indications). Differences in median survival between the RWD studies and their corresponding trial ranged from -32 months to 21 months (IQR -4·2 months to 1·6 months). Low-quality studies were more likely to report superior survival outcomes (23%) compared to higher quality studies (8%) (p = 0.02). CONCLUSION: RWD study quality for novel cancer drugs is low and of insufficient rigour to inform reimbursement decisions and clinical practice. RWD studies seeking publication should provide a completed quality assessment tool on submission. Greater investment in properly designed RWD studies is required.