Author response: An umbrella review of systematic reviews on the impact of the COVID-19 pandemic on cancer prevention and management, and patient needs

Full text Figures and data Side by side Abstract Editor's evaluation eLife digest Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract The relocation and reconstruction of health care resources and systems during the coronavirus disease 2019 (COVID-19) pandemic may have affected cancer care. An umbrella review was undertaken to summarize the findings from systematic reviews on impact of the COVID-19 pandemic on cancer treatment modification, delays, and cancellations; delays or cancellations in screening and diagnosis; psychosocial well-being, financial distress, and use of telemedicine as well as on other aspects of cancer care. Bibliographic databases were searched for relevant systematic reviews with or without meta-analysis published before November 29th, 2022. Abstract, full- text screening, and data extraction were performed by two independent reviewers. AMSTAR-2 was used for critical appraisal of included systematic reviews. Fifty-one systematic reviews were included in our analysis. Most reviews were based on observational studies judged to be at medium and high risk of bias. Only two reviews had high or moderate scores based on AMSTAR-2. Findings suggest treatment modifications in cancer care during the pandemic versus the pre-pandemic period were based on low level of evidence. Different degrees of delays and cancellations in cancer treatment, screening, and diagnosis were observed, with low- and- middle- income countries and countries that implemented lockdowns being disproportionally affected. A shift from in-person appointments to telemedicine use was observed, but utility of telemedicine, challenges in implementation and cost-effectiveness in cancer care were little explored. Evidence was consistent in suggesting psychosocial well-being of patients with cancer deteriorated, and cancer patients experienced financial distress, albeit results were in general not compared to pre-pandemic levels. Impact of cancer care disruption during the pandemic on cancer prognosis was little explored. In conclusion, substantial but heterogenous impact of COVID-19 pandemic on cancer care has been observed. Editor's evaluation This solid work reviews and synthesizes evidence of the impact of the COVID-19 pandemic on a variety of cancer outcomes. The results have potentially important implications for various fields of cancer research as they review evidence spanning from cancer prevention efforts to changes in diagnoses and cancer treatment modalities. https://doi.org/10.7554/eLife.85679.sa0 Decision letter Reviews on Sciety eLife's review process eLife digest The onset of the COVID-19 pandemic disrupted many aspects of human life, not least healthcare. As resources were redistributed towards the crisis, social isolation rules also limited access to medical professionals. In particular, these measures may have affected many aspects of cancer care, such as early detection or treatment. Many studies have aimed to capture the impact of these changes, but most have been observational, with researchers recording events without trying to impose a controlled design. These investigations also often faced limitations such as small sample sizes, or only focusing on one aspect of cancer care. Systemic reviews, which synthetize and assess existing research on a topic, have helped to bypass these constraints. However, they are themselves not devoid of biases. Overall, a clear, unified picture of the impact of COVID-19 on cancer care is yet to emerge. In response, Muka et al. carried an umbrella analysis of 51 systematic reviews on this topic. They used a well-known critical appraisal tool to assess the methodological rigor of each of these studies, while also summarising their findings. This work aimed to capture many aspects of the patients’ experience, from diagnosis to treatment and the financial, psychological, physical and social impact of the disease. The results confirmed that the pandemic had a substantial impact on cancer care, including delays in screening, diagnosis and treatment. Throughout this period cancer patients experienced increased rates of depression, post-traumatic stress and fear of their cancer progressing. The long-term consequences of these disruptions remain to be uncovered. However, Muka et al. also showed that, overall, these conclusions rely on low-quality studies which may have introduced unaccountable biases. In addition, their review highlights that most of the data currently available has been collected in high- and middle-income countries, with evidence lacking from regions of the world with more limited resources. In the short-term, these results indicate that interventions may be needed to mitigate the negative impact of the pandemic on cancer care; in the long-term, they also demonstrate the importance of rigorous systematic reviews in guiding decision making. By shining a light on the ripple effects of certain decisions about healthcare resources, this work could also help to shape the response to future pandemics. Introduction The coronavirus disease 2019 (COVID-19) pandemic and the mitigation measures that were undertaken posed major challenges to cancer care. The rapid spread of COVID-19 and early data showing patients with cancer were at increased risk of morbidity and mortality after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, prompted changes in healthcare delivery (Venkatesulu et al., 2020). These changes included reduction of medical activities, reallocation of healthcare workers, shifting in-person appointments to remote consultations, and limiting access of patients to care facilities (Dhada et al., 2021). Concerns have been raised that disruption of healthcare services might have had multidimensional impact in cancer care. Indeed, several studies have described delays and cancellation in treatment, screening, and diagnosis (Teglia et al., 2022a; Teglia et al., 2022b; Nikolopoulos et al., 2022). For example, two meta-analyses showed that during the pandemic there was a ~50% reduction in breast and cervical cancer screening, and that there was 18.7% reduction for all cancer treatments, with surgical treatment showing the highest reduction (Teglia et al., 2022a; Teglia et al., 2022b). In addition, several studies have highlighted deterioration of psychological well-being of patients with cancer, and psychological, ethical, spiritual, and financial needs of patients with cancer were also affected (Zhang et al., 2022; Kirby et al., 2022). While several systematic reviews have examined the impact of COVID-19 on cancer care, they evaluated different outcomes and periods of the pandemic, and thus the available review findings are rather fragmented (Teglia et al., 2022a; Teglia et al., 2022b; Donkor et al., 2021; Gascon et al., 2022; Hojaij et al., 2020; Legge et al., 2022; Murphy et al., 2022; Gadsden et al., 2022; Majeed et al., 2022). A comprehensive review of impact of COVID-19 on several aspects of cancer would be essential to understand gaps and scale-up evidence-based interventions, including learning lessons for future pandemics. In addition, although systematic reviews are important for public health and policy decision-making during the pandemic, the level of methodological rigor they implemented is unclear. In the current study, we performed an umbrella review of systematic reviews to summarize the impact of COVID-19 on several aspects of cancer care, including treatment, diagnosis, financial, psychological, and social dimensions. We assessed the amount and geographical breadth of the available evidence and methodological rigor of the primary studies included in each review (as assessed by the reviewers) and of the systematic reviews themselves; and summarized the conclusions from different reviews on COVID-19 impact. Results Our search strategy identified 1172 citations. Based on title and abstract screening, we retrieved full texts of 96 articles for further screening. Of those, 45 articles did not meet our eligibility criteria, thus leaving 51 articles to be included in our final analysis. Figure 1 summarizes our screening procedure. No additional study was found from screening of references of the included studies. Figure 1 Download asset Open asset Flowchart of identification, screening, eligibility, inclusion, and exclusion of retrieved studies*. *In the search, we did not include any language restriction filter. However, during full-text screening we included only studies that were in English. **WHO COVID-19 database does not allow to specify the search by both date and month, and the search for this specific database is up to end-December 2022. Any full text (n = 0) that was eligible and published after November 29, 2022, was excluded. Characteristics of the included systematic reviews Of the 51 included systematic reviews, 14 articles also included a quantitative analysis/meta-analysis with one being individual participant meta-analysis (Dhada et al., 2021 ; Teglia et al., 2022a; Teglia et al., 2022b; Nikolopoulos et al., 2022; Zhang et al., 2022; Kirby et al., 2022; Donkor et al., 2021; Gascon et al., 2022; Hojaij et al., 2020; Legge et al., 2022; Murphy et al., 2022; Gadsden et al., 2022; Majeed et al., 2022; Adham et al., 2022; Alom et al., 2021; Ayubi et al., 2021; Garg et al., 2020; Jammu et al., 2021; Lu et al., 2021; Momenimovahed et al., 2021; Mostafaei et al., 2022; Moujaess et al., 2020; Muls et al., 2022; Pacheco et al., 2021; Rohilla et al., 2021; Salehi et al., 2022; Sun et al., 2021; Zapała et al., 2022; Alkatout et al., 2021; Di Cosimo et al., 2022; Fancellu et al., 2022; Ferrara et al., 2022; Hesary and Salehiniya, 2022; Lignou et al., 2022; Mayo et al., 2021; Mazidimoradi et al., 2021; Mazidimoradi et al., 2022; Ng and Hamilton, 2022; Pararas et al., 2022; Riera et al., 2021; Sarich et al., 2022; Sasidharanpillai and Ravishankar, 2022; Tang et al., 2022; Thomson et al., 2020; Vigliar et al., 2020; de Bock et al., 2022). Other key characteristics of the 51 systematic reviews are shown in Table 1 (more extensive details appear in Supplementary file 1a and Supplementary file 2). The median number of bibliographic databases/data sources that were searched was 3; the most searched databases were PubMed (n = 35), Medline (n = 25), Embase (n = 22), Scopus (n = 19), Web of Science (n = 13), and The Cumulative Index to Nursing and Allied Health Literature – CINAHL database (n = 10). One review searched for mobile applications using the iOS App Store and Android Google Play (Lu et al., 2021). The median number of studies included in the systematic reviews was 31 (interquartile range, 15; 51). The type of study designs included across reviews varied, but most reviews included data from observational study designs of cross-sectional and retrospective nature. Twenty-one reviews focused/reported exclusively on studies that include pre-pandemic controls. Twenty reviews provided data only on site-specific cancers, while the rest for any cancer site with or without data on site-specific cancers. Nineteen reviews assessed only one aspect of cancer care, while the rest examined two or more of our pre-defined outcomes. The date of last search varied from April 2020 to May 2022, with 16 reviews ending searches during 2020, 25 during 2021, and 5 during 2022; 4 reviews did not provide information on date of last search. Table 1 Characteristics of included systematic reviews. Author, year of publicationMeta-analysisNumber of included studiesCountries*Pre-pandemic controlsCancer typesAspects assessedLast searchAdham et al., 2022No5GloballyNoH&NMT, O15-Jul-20Alkatout et al., 2021No16Multiple countries, includingUS, TW, BE, NL, JP, IT, UK, AS, CAYesALLDCS, RD28-Dec-20Alom et al., 2021No72Multiple countriesNoAllMT, TL, O1-Sep-20Ayubi et al., 2021Yes34Multiple countriesNoAllPSND, O3-Jan-21Azab and Azzam, 2021No51Multiple countriesNoGliomaMTEnd of 2020Bezerra et al., 2022No8NPNoALLTL01-Apr-2021Crosby and Sharma, 2020No45NPNo/NSH&NMT08-Apr-2020de Bock et al., 2022Yes24Multiple countriesYesALL, BCDelayed and/or canceled treatmentOther aspects21-Mar-2021Dhada et al., 2021No19Multiple countries, including IT, US, UK, NLNoALLDCT, DCS, PSND, TL, FBD, SIA1-Dec-20Di Cosimo et al., 2022Yes56Multiple countriesYesALLMT, DCT, TL, O11-Dec-20Donkor et al., 2021No11Multiple countries, including CN, IR, BR, ZANoALLO3-Aug-20Fancellu et al., 2022No7ITYesCRCDCS, RD31-Jan-22Ferrara et al., 2022No33Multiple countriesYesCVDCT, DCS, RD, RHPV8-Feb-22Gadsden et al., 2022No17Multiple countries, including IN, SL, BAYesALLDCT, O15-Dec-21Garg et al., 2020No212Multiple countriesNoALLMT2-May-20Gascon et al., 2022No23Multiple countriesNoH&NMT, O1-May-20Hesary and Salehiniya, 2022No22Multiple countries, includingIT, UK, PG, NL, CN, IN, JP, TU, IR, SNYesGAMT, DCS, RD, PSND31-Dec-21Hojaij et al., 2020No35Multiple countriesNoH&N, OTOMT, TL, O31-Dec-20Jammu et al., 2021No19Multiple countriesNoALLDCT, PSND, FBD27-Aug-20Kirby et al., 2022No56Multiple countriesNoALLPSND, FBD, SIA31-Mar-21Legge et al., 2022No18Multiple countriesNoALLPSND, FBD, SIA25-May-22Lignou et al., 2022No32Multiple countriesYesPCDCT, RD, TL1-Aug-21Lu et al., 2021No41†NPNoALLTL1-May-20Majeed et al., 2022No60Multiple countriesYes, but NSPCDCT, RD, TL3-Nov-21Mayo et al., 2021Yes13Multiple countries, includingIT, AU, TW, US, FR, NLYesALLDCT, DCS10-Feb-21Mazidimoradi et al., 2021No43Multiple countriesYesCRCMT, DCT, RD1-Jun-21Mazidimoradi et al., 2022No25Multiple countriesYesCRCDCS1-Jun-21Momenimovahed et al., 2021No55Multiple countriesNoALLPSND30-Jun-21Mostafaei et al., 2022No22Multiple countriesNoALLTL1-Jun-21Moujaess et al., 2020No88Multiple countriesNoALLDCT, O15-Apr-20Muls et al., 2022No51Multiple countriesNoALLPSND1-Oct-21Murphy et al., 2022No37Multiple countriesNoALLTL31-Mar-21Ng and Hamilton, 2022Yes31Multiple countriesYesBCDCS, RD1-Oct-20Nikolopoulos et al., 2022No15Multiple countriesYes, but NSGCMT, DCT, RD, PSND10-Feb-21Pacheco et al., 2021No9Multiple countries, includingUS, IT, CN, SP, UK, IRNoALLDCT, ONPPararas et al., 2022Yes10Multiple countriesYesCRCONPPascual et al., 2022No12Multiple countries from low- and middle-income countriesYes, but NSSurgical Neuro-OncologyMD, RD, TL, O01-Sep- 2021Piras et al., 2022No281Multiple countriesNoALLMT, DCT, SIA, PSND31-Dec-2021Riera et al., 2021No62Multiple countriesYesALLDCTNPRohilla et al., 2021No6INNoALLPSND, O3-Feb-21Salehi et al., 2022No16Multiple countriesNoALLTL1-Apr-21Sarich et al., 2022Yes44Multiple countriesYesNARF5-Nov-20Sasidharanpillai and Ravishankar, 2022Yes7Multiple countries, includingSL, IT, CA, SC, BE, USYesCVDCT, RD1-Sep-21Sun et al., 2021No6IT, AM, UKNoBCMT1-Feb-21Tang et al., 2022Yes14TU, CN, UK, IT, DN, AS, AUYesCRCO12-Jan-22Teglia et al., 2022aYes39Multiple countriesYesBC, CRC, CVDCT, RD12-Dec-21Teglia et al., 2022bYes47Multiple countriesYesALLDCT12-Dec-21Thomson et al., 2020Yes54NPYesALLO1-Jun-21Vigliar et al., 2020Yes41‡Multiple countriesYesALLDCS, RD30-Apr-20Zapała et al., 2022No160NPNoALLDCT, PSND, TLNPZhang et al., 2022Yes40Multiple countriesNoALLPSND31-Jan-22 * Multiple countries refer to inclusion of studies for final analysis that used data from more than one country. If complete information on location from all primary studies were provided, then specific countries were listed. † Apps. ‡ Respondents. AM, America; BC; AS, Austria; AU, Australia; BA, Bangladesh; BC, breast cancer; BE, Belgium; BR, Brazil; CA, Canada; China; CRC, colorectal cancer; CV, cervical cancer; DN, Denmark; FR, France; GA, gastric cancer; GC, gynecological cancer; H&N, head and neck cancer; IN, India; IR, Iran; IT, Italy; JP, Japan; NA, not applicable; NL, Netherlands; NP, not provided; OTO, otorhinolaryngology cancer; PC, pediatric cancer; PG, Portugal; SC, Scotland; SL, Slovenia or Sri Lanka; SN, Singapore; SP, Spain; TU, Turkey; TW, Taiwan; UK, United Kingdom; United States; ZA, Zambia;MT, modification of treatment; DCT, delayed and/or canceled treatment; DCS, delayed and canceled screening; RD, reduced diagnosis: RHPV, reduced uptake of HPV vaccination; TL, telemedicine; PSND, psychological needs/distress; FBD, financial burden/distress; SIA, social isolation; O, other aspects. Geographical distribution Out of 51 reviews, 46 provided some information on geographical distribution of the included primary studies. Of those, most reviews provided data from different countries, while only two studies (3.9%) focused on data from India (Rohilla et al., 2021) and Italy (Fancellu et al., 2022) exclusively. Also the majority of the evidence was derived from high- and middle-income countries. Risk of bias of primary studies included in the systematic reviews and GRADE assessments Of the 51 reviews, 32 assessed risk of bias of the included studies (Table 2 and details in Supplementary file 1b). Thirteen different risks of bias checklists were used, and the most common checklists used to assess methodological rigor were Newcastle-Ottawa Scale (NOS) (n = 10) and Joanna Briggs Institute tools (n = 7). Of the systematic reviews that assess methodological rigor of the individual studies, 8 concluded strong evidence, 19 mixed evidence, 3 weak evidence, and 2 did not provide any results. Excluding the NOS assessments [since NOS has been criticized to not provide accurate assessment of methodological rigor (Stang, 2010)], the respective numbers were 3, 14, 3, and 2. Only two reviews used GRADE (Grading of Recommendations, Assessment, Development and Evaluations), concluding low to moderate certainty in the results. Table 2 Methodological rigor of included reviews. AuthorChecklist useMethodological rigor conclusion categoryGRADEAdham et al., 2022CEBMNot providedNot providedAlkatout et al., 2021NOSStrong evidenceNot providedAlom et al., 2021NHLBI, NIHNot providedNot providedAyubi et al., 2021Not appliedNot providedNot providedAzab and Azzam, 2021Not appliedNot providedNot providedBezerra et al., 2022Not appliedNot providedNot providedDi Cosimo et al., 2022CLARITYMixed/IntermediateNot providedCrosby and Sharma, 2020Not appliedNot providedNot providedde Bock et al., 2022ROBINS-IStrong evidenceNot providedDhada et al., 2021CASP, NHLBI, NIHMixed/IntermediateNot providedDonkor et al., 2021JBIWeakNot providedFancellu et al., 2022Not appliedNot providedNot providedFerrara et al., 2022NOSStrong evidenceNot providedGadsden et al., 2022JBI, ROBINS-IMixed/IntermediateNot providedGarg et al., 2020Not appliedNot providedNot providedGascon et al., 2022Agree IIMixed/IntermediateNot providedHesary and Salehiniya, 2022NOSMixed/IntermediateNot providedHojaij et al., 2020Not appliedNot providedNot providedJammu et al., 2021Not appliedNot providedNot providedKirby et al., 2022JBI, CHECMixed/IntermediateNot providedLegge et al., 2022MMATStrong evidenceNot providedLignou et al., 2022Not appliedNot providedNot providedLu et al., 2021MARSMixed/IntermediateNot providedMajeed et al., 2022Not appliedNot providedLow to moderate certaintyMayo et al., 2021NOSMixed/IntermediateModerate to highMazidimoradi et al., 2021NOSMixed/IntermediateNot providedMazidimoradi et al., 2022NOSStrong evidenceNot providedMomenimovahed et al., 2021Not appliedNot providedNot providedMostafaei et al., 2022JBIMixed/IntermediateNot providedMoujaess et al., 2020Not appliedNot providedNot providedMuls et al., 2022MMATMixed/IntermediateNot providedMurphy et al., 2022JBI, CHECMixed/IntermediateNot providedNg and Hamilton, 2022NOSMixed/IntermediateNot providedNikolopoulos et al., 2022NOSMixed/IntermediateNot providedPacheco et al., 2021JBI, ROBINS-IWeakNot providedPararas et al., 2022NOSStrong evidenceNot providedPascual et al., 2022Not appliedNot providedNot providedPiras et al., 2022Not appliedNot providedNot providedRiera et al., 2021ROBINS-IMixed/IntermediateNot providedRohilla et al., 2021Not appliedNot providedNot providedSalehi et al., 2022Not appliedNot providedNot providedSarich et al., 2022ROBINS-IWeak evidenceNot providedSasidharanpillai and Ravishankar, 2022NHLBI, NIHStrong evidenceNot providedSun et al., 2021Not appliedNot providedNot providedTang et al., 2022NOSStrong evidenceNot providedTeglia et al., 2022aCASPMixed/IntermediateNot providedTeglia et al., 2022bCASPMixed/IntermediateNot providedThomson et al., 2020ASTROMixed/IntermediateNot providedVigliar et al., 2020Not applicableNot providedNot providedZapała et al., 2022Not appliedNot providedNot providedZhang et al., 2022JBIMixed/IntermediateNot provided CEBM, Critical appraisal tool of qualitative studies from Centre of Evidence-based Medicine (CEBM), University of Oxford; ASTRO, The American Society of Radiation Oncology; CASP, https://casp-uk.net/casp-tools-checklists/; CHEC, Consensus on Health Economic Criteria: CLARITY, ‘Risk of bias instrument for cross-sectional surveys of attitudes and practices’ from the CLARITY Group at McMaster University; JBI, Joanna Briggs Institute; MARS, Mobile Apps Rating Scale; MMAT, Mixed Methods Appraisal Tool; NHLBI, NHI, National Institute of Health Checklist; NOS, Newcastle-Ottawa Quality Assessment: RBC, Risk of Bias Checklist for Prevalence Studies by Hoy et al., 2012. Methodological rigor of included systematic reviews Table 3 shows the AMSTAR-2 evaluations for the included systematic reviews. Only two reviews scored moderate to high quality, while the rest were evaluated as low or critically low quality due to not meeting one or more of the seven domains considered critical. Most of the studies did not provide the of studies during the full-text screening, and did not for methodological rigor of included studies the results of the reviews. Table 3 Methodological assessment of the included reviews – AMSTAR-2 evaluation year of et al., et al., et al., et al., and Azzam, et al., and Sharma, Bock et al., et al., Cosimo et al., et al., et al., et al., et al., et al., et al., and Salehiniya, et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., and Hamilton, et al., et al., et al., et al., et al., et al., et al., et al., et al., and Ravishankar, et al., et al., et al., et al., et al., et al., et al., et al., AMSTAR-2 assessment review an accurate and comprehensive of the results of the available studies that the of review has more than one but critical may provide an accurate of the results of the available review has a critical and may not provide an accurate and comprehensive of the available studies that the of or critically review has more than one critical and not be on to provide an accurate and comprehensive of the available studies. the research and inclusion for the review include the of the of the review an that the review methods were to the of the review and did the any from the the review their of the study designs for inclusion in the the review use a comprehensive search the review study in the review data extraction in the review provide a of studies and the the review the included studies in the review use a for the risk of bias in individual studies that were included in the the review on the sources of for the studies included in the If meta-analysis was performed did the review use methods for of If meta-analysis was did the review assess the impact of in individual studies on the results of the meta-analysis or other evidence the review for in individual studies the results of the the review provide a and any in the results of the If they performed quantitative did the review an of bias study and impact on the results of the the review any sources of of including any they for the * The review scored study used a to methodological and only GRADE assessment was provided without a for methodological † participant meta-analysis and thus not the not applicable; Results and conclusions of systematic reviews and of meta-analyses The results and conclusions of the eligible systematic reviews are in Supplementary file for various aspects of cancer care. Table 4 the and for the systematic reviews that used meta-analysis as well as Figure 2 a of findings of this umbrella we some key findings for each type of of treatment Figure 2 Download asset Open asset Table 4 of the meta-analysis of et al., Zhang et al., of cancer Di Cosimo et al., of of of in of remote use of use of screening de Bock et al., during the COVID-19 pandemic compared to the pre-pandemic during the COVID-19 pandemic compared to the pre-pandemic during the COVID-19 pandemic compared to the pre-pandemic Mayo et al., breast cervical Ng and Hamilton, breast cancer breast cancer breast