Association between the COVID-19 pandemic and first cancer treatment modality: a population-based cohort study.

BACKGROUND: Physicians were directed to prioritize using nonsurgical cancer treatment at the beginning of the COVID-19 pandemic. We sought to quantify the impact of this policy on the modality of first cancer treatment (surgery, chemotherapy, radiotherapy or no treatment). METHODS: In this population-based study using Ontario data from linked administrative databases, we identified adults diagnosed with cancer from January 2016 to November 2020 and their first cancer treatment received within 1 year postdiagnosis. Segmented Poisson regressions were applied to each modality to estimate the change in mean 1-year recipient volume per thousand patients (rate) at the start of the pandemic (the week of Mar. 15, 2020) and change in the weekly trend in rate during the pandemic (Mar. 15, 2020, to Nov. 7, 2020) relative to before the pandemic (Jan. 3, 2016, to Mar. 14, 2020). RESULTS: We included 321 535 people diagnosed with cancer. During the first week of the COVID-19 pandemic, the mean rate of receiving upfront surgery over the next year declined by 9% (rate ratio 0.91, 95% confidence interval [CI] 0.88-0.95), and chemotherapy and radiotherapy rates rose by 30% (rate ratio 1.30, 95% CI 1.23-1.36) and 13% (rate ratio 1.13, 95% CI 1.07-1.19), respectively. Subsequently, the 1-year rate of upfront surgery increased at 0.4% for each week (rate ratio 1.004, 95% CI 1.002-1.006), and chemotherapy and radiotherapy rates decreased by 0.9% (rate ratio 0.991, 95% CI 0.989-0.994) and 0.4% (rate ratio 0.996, 95% CI 0.994-0.998), respectively, per week. Rates of each modality resumed to prepandemic levels at 24-31 weeks into the pandemic. INTERPRETATION: An immediate and sustained increase in use of nonsurgical therapy as the first cancer treatment occurred during the first 8 months of the COVID-19 pandemic in Ontario. Further research is needed to understand the consequences.

Early survival for patients newly diagnosed with cancer during COVID-19 in Ontario, Canada: A population-based cohort study.

BACKGROUND: Little is known about the association between the COVID-19 pandemic and early survival among newly diagnosed cancer patients. METHODS: This retrospective population-based cohort study used linked administrative datasets from Ontario, Canada. Adults (≥18 years) who received a cancer diagnosis between March 15 and December 31, 2020, were included in a pandemic cohort, while those diagnosed during the same dates in 2018/2019 were included in a pre-pandemic cohort. All patients were followed for one full year after the date of diagnosis. Cox proportional hazards regression models were used to assess survival in relation to the pandemic, patient characteristics at diagnosis, and the modality of first cancer treatment as a time-varying covariate. Interaction terms were explored to measure the pandemic association with survival for each cancer type. RESULTS: Among 179,746 patients, 53,387 (29.7%) were in the pandemic cohort and 37,741 (21.0%) died over the first post-diagnosis year. No association between the pandemic and survival was found when adjusting for patient characteristics at diagnosis (HR 0.99 [95% CI 0.96-1.01]), while marginally better survival was found for the pandemic cohort when the modality of treatment was additionally considered (HR 0.97 [95% CI 0.95-0.99]). When examining each cancer type, only a new melanoma diagnosis was associated with a worse survival in the pandemic cohort (HR 1.25 [95% CI 1.05-1.49]). CONCLUSIONS: Among patients able to receive a cancer diagnosis during the pandemic, one-year overall survival was not different than those diagnosed in the previous 2 years. This study highlights the complex nature of the COVID-19 pandemic impact on cancer care.

Imaging and physician visits at cancer diagnosis: COVID -19 pandemic impact on cancer care.

BACKGROUND: Little is known about the COVID-19 pandemic impact on the provision of diagnostic imaging and physician visits at cancer diagnosis. METHODS: We used administrative databases from Ontario, Canada, to identify MRI/CT/ultrasound scans and in-person/virtual physician visits conducted with cancer patients within 91 days around the date of diagnosis in 2016-2020. In separate segmented regression procedures, we assessed the trends in weekly volume of these services per thousand cancer patients in prepandemic (June 26, 2016 to March 14, 2020), the change in mean volume at the start of the pandemic, and the additional change in weekly volume during the pandemic (March 15, 2020, to September 26, 2020). RESULTS: Totally, 403,561 cancer patients were included. On March 15, 2020 (COVID-19 arrived), mean scan volume decreased by 12.3% (95% CI: 6.4%-17.9%) where ultrasound decreased the most by 31.8% (95% CI: 23.9%-37.0%). Afterward, the volume of all scans increased further by 1.6% per week (95% CI: 1.3%-2.0%), where ultrasound increased the fastest by 2.4% (95% CI: 1.8%-2.9%). Mean in-person visits dropped by 47.4% when COVID-19 started (95% CI: 41.6%-52.6%) while virtual visits rose by 55.15-fold (95% CI: 4927%-6173%). In the pandemic (until September 26, 2020), in-person visits increased each week by 2.6% (95% CI: 2.0%-3.2%), but no change was observed for virtual visits (p -value = 0.10). CONCLUSIONS: Provision of diagnostic imaging and virtual visits at cancer diagnosis has been increasing since the start of COVID-19 and has exceeded prepandemic utilization levels. Future work should monitor the impact of these shifts on quality of delivered care.

Incident Cancer Detection During the COVID-19 Pandemic.

BACKGROUND: Resource restrictions were established in many jurisdictions to maintain health system capacity during the COVID-19 pandemic. Disrupted healthcare access likely impacted early cancer detection. The objective of this study was to assess the impact of the pandemic on weekly reported cancer incidence. PATIENTS AND METHODS: This was a population-based study involving individuals diagnosed with cancer from September 25, 2016, to September 26, 2020, in Ontario, Canada. Weekly cancer incidence counts were examined using segmented negative binomial regression models. The weekly estimated backlog during the pandemic was calculated by subtracting the observed volume from the projected/expected volume in that week. RESULTS: The cohort consisted of 358,487 adult patients with cancer. At the start of the pandemic, there was an immediate 34.3% decline in the estimated mean cancer incidence volume (relative rate, 0.66; 95% CI, 0.57-0.75), followed by a 1% increase in cancer incidence volume in each subsequent week (relative rate, 1.009; 95% CI, 1.001-1.017). Similar trends were found for both screening and nonscreening cancers. The largest immediate declines were seen for melanoma and cervical, endocrinologic, and prostate cancers. For hepatobiliary and lung cancers, there continued to be a weekly decline in incidence during the COVID-19 period. Between March 15 and September 26, 2020, 12,601 fewer individuals were diagnosed with cancer, with an estimated weekly backlog of 450. CONCLUSIONS: We estimate that there is a large volume of undetected cancer cases related to the COVID-19 pandemic. Incidence rates have not yet returned to prepandemic levels.

Timeliness and Modality of Treatment for New Cancer Diagnoses During the COVID-19 Pandemic in Canada.

Importance: The impact of COVID-19 on the modality and timeliness of first-line cancer treatment is unclear yet critical to the planning of subsequent care. Objective: To explore the association of the COVID-19 pandemic with modalities of and wait times for first cancer treatment. Design, Setting, and Participants: This retrospective population-based cohort study using administrative data was conducted in Ontario, Canada, among adults newly diagnosed with cancer between January 3, 2016, and November 7, 2020. Participants were followed up from date of diagnosis for 1 year, until death, or until June 26, 2021, whichever occurred first, to ensure a minimum of 6-month follow-up time. Exposures: Receiving a cancer diagnosis in the pandemic vs prepandemic period, using March 15, 2020, the date when elective hospital procedures were halted. Main Outcomes and Measures: The main outcome was a time-to-event variable describing number of days from date of diagnosis to date of receiving first cancer treatment (surgery, chemotherapy, or radiation) or to being censored. For each treatment modality, a multivariable competing-risk regression model was used to assess the association between time to treatment and COVID-19 period. A secondary continuous outcome was defined for patients who were treated 6 months after diagnosis as the waiting time from date of diagnosis to date of treatment. Results: Among 313 499 patients, the mean (SD) age was 66.4 (14.1) years and 153 679 (49.0%) were male patients. Those who were diagnosed during the pandemic were less likely to receive surgery first (subdistribution hazard ratio [sHR], 0.97; 95% CI, 0.95-0.99) but were more likely to receive chemotherapy (sHR, 1.26; 95% CI, 1.23-1.30) or radiotherapy (sHR, 1.16; 95% CI, 1.13-1.20) first. Among patients who received treatment within 6 months from diagnosis (228 755 [73.0%]), their mean (SD) waiting time decreased from 35.1 (37.2) days to 29.5 (33.6) days for surgery, from 43.7 (34.1) days to 38.4 (30.6) days for chemotherapy, and from 55.8 (41.8) days to 49.0 (40.1) days for radiotherapy. Conclusions and Relevance: In this cohort study, the pandemic was significantly associated with greater use of nonsurgical therapy as initial cancer treatment. Wait times were shorter in the pandemic period for those treated within 6 months of diagnosis. Future work needs to examine how these changes may have affected patient outcomes to inform future pandemic guideline development.

Incident Cancer Detection During Multiple Waves of COVID-19: The Tsunami After the Earthquake.

No population-based study exists to demonstrate the full-spectrum impact of COVID-19 on hindering incident cancer detection in a large cancer system. Building upon our previous publication in JNCCN, we conducted an updated analysis using 12 months of new data accrued in the pandemic era (extending the study period from September 26, 2020, to October 2, 2021) to demonstrate how multiple COVID-19 waves affected the weekly cancer incidence volume in Ontario, Canada, and if we have fully cleared the backlog at the end of each wave.

Cancer Patients First Treated with Chemotherapy: Are They More Likely to Receive Surgery in the Pandemic?

Due to the ramping down of cancer surgery in early pandemic, many newly diagnosed patients received other treatments first. We aimed to quantify the pandemic-related shift in rate of surgery following chemotherapy. This is a retrospective population-based cohort study involving adults diagnosed with cancer between 3 January 2016 and 7 November 2020 in Ontario, Canada who received chemotherapy as first treatment within 6-months of diagnosis. Competing-risks regression models with interaction effects were used to quantify the association between COVID-19 period (receiving a cancer diagnosis before or on/after 15 March 2020) and receipt of surgical reSection 9-months after first chemotherapy. Among 51,653 patients, 8.5% (n = 19,558) of them ultimately underwent surgery 9-months after chemotherapy initiation. Receipt of surgery was higher during the pandemic than before (sHR 1.07, 95% CI 1.02-1.13). Material deprivation was independently associated with lower receipt of surgery (least vs. most deprived quintile: sHR 1.11, 95% CI 1.04-1.17), but did not change with the pandemic. The surgical rate increase was most pronounced for breast cancer (sHR 1.13, 95% CI 1.06-1.20). These pandemic-related shifts in cancer treatment requires further evaluations to understand the long-term consequences. Persistent material deprivation-related inequity in cancer surgical access needs to be addressed.

Are patients with cancer at higher risk of COVID-19-related death? A systematic review and critical appraisal of the early evidence.

BACKGROUND: Early reports suggested that COVID-19 patients with cancer were at higher risk of COVID-19-related death. We conducted a systematic review with risk of bias assessment and synthesis of the early evidence on the risk of COVID-19-related death for COVID-19 patients with and without cancer. METHODS AND FINDINGS: We searched Medline/Embase/BioRxiv/MedRxiv/SSRN databases to 1 July 2020. We included cohort or case-control studies published in English that reported on the risk of dying after developing COVID-19 for people with a pre-existing diagnosis of any cancer, lung cancer, or haematological cancers. We assessed risk of bias using tools adapted from the Newcastle-Ottawa Scale. We used the generic inverse-variance random-effects method for meta-analysis. Pooled odds ratios (ORs) and hazard ratios (HRs) were calculated separately. Of 96 included studies, 54 had sufficient non-overlapping data to be included in meta-analyses (>500,000 people with COVID-19, >8000 with cancer; 52 studies of any cancer, three of lung and six of haematological cancers). All studies had high risk of bias. Accounting for at least age consistently led to lower estimated ORs and HRs for COVID-19-related death in cancer patients (e.g. any cancer versus no cancer; six studies, unadjusted OR=3.30,95%CI:2.59-4.20, adjusted OR=1.37,95%CI:1.16-1.61). Adjusted effect estimates were not reported for people with lung or haematological cancers. Of 18 studies that adjusted for at least age, 17 reported positive associations between pre-existing cancer diagnosis and COVID-19-related death (e.g. any cancer versus no cancer; nine studies, adjusted OR=1.66,95%CI:1.33-2.08; five studies, adjusted HR=1.19,95%CI:1.02-1.38). CONCLUSIONS: The initial evidence (published to 1 July 2020) on COVID-19-related death in people with cancer is characterised by multiple sources of bias and substantial overlap between data included in different studies. Pooled analyses of non-overlapping early data with adjustment for at least age indicated a significantly increased risk of COVID-19-related death for those with a pre-existing cancer diagnosis.

Factors associated with cancer treatment delay: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Treatment delays are significantly associated with increased mortality risk among adult cancer patients; however, factors associated with these delays have not been robustly evaluated. This review and meta-analysis will evaluate factors associated with treatment delays among patients with five common cancers. METHODS AND ANALYSIS: Scientific databases including Ovid MEDLINE, Elsevier Embase, EBSCOhost CINAHL Plus Full Text, Elsevier Scopus and ProQuest Dissertations and Theses Global will be searched to identify relevant articles published between January 2000 and October 2021. Research articles published in the USA evaluating factors associated with treatment delay among breast, lung, prostate, cervical or colorectal adult cancer patients will be included. The primary outcome of the meta-analysis will be the pooled adjusted and unadjusted odds of treatment delay for patient, disease, provider and system-level factors defined according to specified time intervals. The secondary outcomes will be mean or median treatment delay for each cancer site according to first treatment and the influence of factors on the pooled mean treatment delay for each cancer site (via meta-regression analyses). Results from qualitative and mixed-methods studies will be narratively synthesised. Three reviewers will independently screen records generated from the search and two reviewers will independently extract data following a consensus agreement. Statistical heterogeneity will be assessed with a standard I2 test and funnel plots will be conducted to evaluate publication bias. Risk of bias will be assessed independently by two authors using validated tools according to the article's study design. ETHICS AND DISSEMINATION: Formal ethical approval is not required because the work is being carried out on publicly accessible studies. The findings of this review will be disseminated through a peer-reviewed scientific journal, academic conferences, social media, and key stakeholders. PROSPERO REGISTRATION NUMBER: CRD42021293131.

The risk of contracting SARS-CoV-2 or developing COVID-19 for people with cancer: A systematic review of the early evidence.

BACKGROUND: The early COVID-19 literature suggested that people with cancer may be more likely to be infected with SARS-CoV-2 or develop COVID-19 than people without cancer, due to increased health services contact and/or immunocompromise. While some studies were criticised due to small patient numbers and methodological limitations, they created or reinforced concerns of clinicians and people with cancer. These risks are also important in COVID-19 vaccine prioritisation decisions. We performed a systematic review to critically assess and summarise the early literature. METHODS AND FINDINGS: We conducted a systematic search of Medline/Embase/BioRxiv/MedRxiv/SSRN databases including peer-reviewed journal articles, letters/commentaries, and non-peer-reviewed pre-print articles for 1 January-1 July 2020. The primary endpoints were diagnosis of COVID-19 and positive SARS-CoV-2 test. We assessed risk of bias using a tool adapted from the Newcastle-Ottawa Scale. Twelve studies were included in the quantitative synthesis. All four studies of COVID-19 incidence (including 24,181,727 individuals, 125,649 with pre-existing cancer) reported that people with cancer had higher COVID-19 incidence rates. Eight studies reported SARS-CoV-2 test positivity for > 472,000 individuals, 48,370 with pre-existing cancer. Seven of these studies comparing people with any and without cancer, were pooled using random effects [pooled odds ratio 0.91, 95 %CI: 0.57-1.47; unadjusted for age, sex, or comorbidities]. Two studies suggested people with active or haematological cancer had lower risk of a positive test. All 12 studies had high risk of bias; none included universal or random COVID-19/SARS-CoV-2 testing. CONCLUSIONS: The early literature on susceptibility to SARS-CoV-2/COVID-19 for people with cancer is characterised by pervasive biases and limited data. To provide high-quality evidence to inform decision-making, studies of risk of SARS-CoV-2/COVID-19 for people with cancer should control for other potential modifiers of infection risk, including age, sex, comorbidities, exposure to the virus, protective measures taken, and vaccination, in addition to stratifying analyses by cancer type, stage at diagnosis, and treatment received.

Prioritising locations for radiotherapy equipment in Brazil: a cross-sectional, population-based study and development of a LINAC shortage index.

BACKGROUND: Similarly to several other upper-middle-income countries, there is a major shortfall in radiotherapy services for the treatment of cancer in Brazil. In this study, we developed the linear accelerator (LINAC) shortage index to assess the LINAC shortage and support the prioritisation of new LINAC distribution in Brazil. METHODS: This cross-sectional, population-based study used data from the National Cancer Institute 2020 Cancer estimates, the Ministry of Health 2019 radiotherapy census, the Minister of Health radiotherapy expansion programme progress reports, and the Fundação Oncocentro de São Paulo public database of the Cancer Hospital Registry of the State of São Paulo to calculate the LINAC shortage index. Data collected were number of new cancer cases in Brazil, number of LINACs per region and state, number of cancer cases treated with radiotherapy, patient state of residence, and radiotherapy treatment centre and location. National, regional, and state-level data were collected for analysis. LINAC numbers, cancer incidence, geographical distribution, and radiotherapy needs were estimated. A LINAC shortage index was calculated as a relative measure of LINAC demand compared with supply based on number of new cancer cases, number of patients requiring radiotherapy, and the number of LINCAS in the region or state. We then built a prioritisation framework using the LINAC shortage index, cancer incidence, and geographical factors. Finally, using patient-level public cancer registry data from the Fundação Oncocentro de São Paulo and Google maps, we estimated the geospatial distance travelled by patients with cancer from their state of residence to radiotherapy treatment in São Paulo from 2005-14. Non-parametric statistics were used for analysis. FINDINGS: Data were collected between Feb 2 and Dec 31, 2021. In 2020, there were 625 370 new cancer cases in Brazil and 252 LINAC machines. The number of LINACs was inadequate in all Brazilian regions, with a national LINAC shortage index of 221 (ie, 121% less than the required radiotherapy capacity). The LINAC shortage index was higher in the midwest (326), north (313), and northeast (237) regions, than the southeast (210) and south (192) regions. Four states (Tocantins, Acre, Amapá, and Roraima) in the north region were ranked first on the prioritisation rank due to no availability of LINACs. There was an association between LINAC shortage index and the number of patients who travelled to receive radiotherapy (p<0·0001). Patients living in the midwest (793 km), north (2835 km), and northeast (2415 km) regions travelled significantly longer average distances to receive radiotherapy treatment in São Paulo than patients living in the southeast or south regions (p=0·032). The reduced number of LINACs in these regions was associated with longer distance travelled (p=0·032). INTERPRETATION: There is substantial discordance between distribution of cancer cases and LINAC availability in Brazil. We developed a tool using the LINACs shortage index to help prioritise the development of radiotherapy infrastructure across Brazil; this approach might also be useful in other health systems. FUNDING: None.

Assessing the Impact of the COVID-19 Pandemic on Emergency Department Use for Patients Undergoing Cancer-Directed Surgeries.

Emergency department (ED) use is a concern for surgery patients, physicians and health administrators particularly during a pandemic. The objective of this study was to assess the impact of the pandemic on ED use following cancer-directed surgeries. This is a retrospective cohort study of patients undergoing cancer-directed surgeries comparing ED use from 7 January 2018 to 14 March 2020 (pre-pandemic) and 15 March 2020 to 27 June 2020 (pandemic) in Ontario, Canada. Logistic regression models were used to (1) determine the association between pandemic vs. pre-pandemic periods and the odds of an ED visit within 30 days after discharge from hospital for surgery and (2) to assess the odds of an ED visit being of high acuity (level 1 and 2 as per the Canadian Triage and Acuity Scale). Of our cohort of 499,008 cancer-directed surgeries, 468,879 occurred during the pre-pandemic period and 30,129 occurred during the pandemic period. Even though there was a substantial decrease in the general population ED rates, after covariate adjustment, there was no significant decrease in ED use among surgical patients (OR 1.002, 95% CI 0.957-1.048). However, the adjusted odds of an ED visit being of high acuity was 23% higher among surgeries occurring during the pandemic (OR 1.23, 95% CI 1.14-1.33). Although ED visits in the general population decreased substantially during the pandemic, the rate of ED visits did not decrease among those receiving cancer-directed surgery. Moreover, those presenting in the ED post-operatively during the pandemic had significantly higher levels of acuity.

Report from the Ready for the Next Round Thought-Leadership Roundtables on Building Resilience in Cancer Care and Control in Canada-Colorectal Cancer Canada; 2021.

(1) Background: The COVID-19 pandemic illuminated vulnerabilities in the Canadian health care system and exposed gaps and challenges across the cancer care continuum. Canada is experiencing significant disruptions to cancer-related services, and the impact these disruptions (delays/deferrals/cancellations) have on the health care system and patients are yet to be determined. Given the potential adverse ramifications, how can Canada's health care systems build resilience for future threats? (2) Methods: To answer this question, CCC facilitated a series of four thought-leadership roundtables, each representing the views of four different stakeholder groups: patients, physicians, health care system leaders, and researchers. (3) Results: Six themes of strength were identified to serve as a springboard for building resilience including, (1) advancing virtual care and digital health technologies to prevent future interruptions in cancer care delivery. (2) developing real-time data metrics, data sharing, and evidence-based decision-making. (3) enhancing public-private-non-profit partnerships to advance research and strengthen connections across the system. (4) advancing patient-centricity in cancer research to drive and encourage precision medicine approaches to care. (5) investing in training and hiring a robust supply of health care human resources. (6) implementing a national strategy and infrastructure to ensure inter-provincial collaborative data sharing (4). Conclusions: A resilient health care system that can respond to shocks and threats is not an emergency system; it is a robust everyday system that can respond to emergencies.

Impact of the COVID-19 pandemic on skin cancer diagnosis: A population-based study.

BACKGROUND: The COVID-19 pandemic has been unprecedented and has led to drastic reductions in non-urgent medical visits. Deferral of these visits may have critical health impact, including delayed diagnosis for melanoma and other skin cancers. We examined the influence of the pandemic on skin biopsy rates in a large population-based cohort. METHODS: Using a universal health care claims dataset from Ontario, we examined skin biopsies from January 6, 2020 to September 27, 2020, and compared these to the same period for 2019. Those diagnosed with anogenital cancers, younger than 20 years, residing out-of-province and with lapses in coverage were excluded. The sensitivity and specificity of claims diagnoses compared to a validated algorithm to identify keratinocyte carcinoma (KC), or to the cancer registry for melanoma was evaluated. Factors associated with biopsy during the early pandemic were investigated with modified Poisson regression. RESULTS: A precipitous drop in total skin biopsies (15% of expected), biopsies for KC (18%) and melanoma (27%) was seen with the onset of COVID-19 cases (p<0.01). Claims diagnoses were of high specificity for KC (99%), and for melanoma (98%), though sensitivity was less (61%, 28% respectively). In adjusted analysis, the elderly (80+ years), females and residents of certain regions were less likely to be biopsied during the pandemic. Subsequently, there were substantial improvements in biopsy rates over 10 weeks. However, compared to 2019, a large backlog of expected cases still remained 28 weeks after lockdown (45,710 all biopsy, 9,104 KC, 595 melanoma). INTERPRETATION: A drastic reduction in skin biopsies is noted early in the COVID-19 pandemic; this disproportionately affected the elderly, females and certain geographic regions. Though biopsies subsequently increased, a large backlog of cases remained after almost half a year. This will have implications for downstream care of skin cancer. Efforts should be made to limit diagnostic delay.

Mortality due to cancer treatment delay: systematic review and meta-analysis.

OBJECTIVE: To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Published studies in Medline from 1 January 2000 to 10 April 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models. RESULTS: The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings. CONCLUSIONS: Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.