enhancing ovarian cancer care: a systematic review of

RESEARCH ARTICLE Open Access

Enhancing ovarian cancer care: asystematic review of guideline adherenceand clinical variationKahren M. White1,2* , Holly Seale1 and Reema Harrison1

Abstract

Background: Clinical variation in ovarian cancer care has been reported internationally. Using Wennberg’s classificationof clinical variation as effective care we can conceptualise variation through deviation from clinical guidelines. The aim ofthis review was to address knowledge gaps in the effectiveness of attempts to reduce unwarranted clinicalvariation through addressing the following questions: What is the evidence of guideline adherence in ovariancancer and its deviation?; what are the key factors associated with variation in guideline adherence in ovariancancer care?; and what quality improvement approaches have been used and what is the evidence of theireffectiveness in enhancing guideline adherence in ovarian cancer care?.

Methods: Keywords and synonyms for the major concepts of ovarian cancer, guideline adherence and safetywere developed and combined to form the search strategy. Systematic searches of four electronic databaseswere undertaken of publications from January 2007 to November 2018. Retrieved articles were assessed against theeligibility criteria to determine those for inclusion.

Results: Thirty-two papers were included in the review with three broad groupings identified: adherence to anddeviation from guidelines (either local, national or international guidelines); factors impacting guidelines adherence;and quality improvement approaches.

Conclusions: Unwarranted clinical variation may be used as a marker for the effectiveness of a health system, basedon the outcome of this systematic review. This review found that the implementation of quality indicators through aformal quality improvement program lead to improvements in guideline adherent care. Further research on outcomesof implementing quality improvement programs in ovarian cancer care will improve the ability to implement centralisedcare and further identify factors that to improve outcomes in ovarian cancer care.

Keywords: Unwarranted clinical variation, Ovarian cancer, Quality improvement, Effective care

IntroductionClinical variation in healthcare describes differences inhealthcare practice, processes or outcomes for reasonssuch as the complexity of a patient’s illness, the burden ofillness in different populations, or administrative differ-ences, such as different coding of the same issue [1]. Suchvariations are evident throughout healthcare systems andservices internationally and reflect natural differences be-tween the individuals and population groups receiving care.

Clinical variation in ovarian cancer care has beenreported internationally [2–4]. Variation from 5 to 55%has been reported in the receipt of neoadjuvant chemo-therapy for women with stage IIIC and IV epithelialovarian cancer in hospitals that have high volume ofboth surgery and chemotherapy for ovarian cancer [2].A population based study from Australia found variationin the provision of standard chemotherapy treatment forwomen older than 70 years with ovarian cancer, with68% of these women not receiving standard chemother-apy [5]. Variation in surgical staging, including adher-ence to guidelines, was found in a Canadian study, with

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* Correspondence: [email protected] of Public Health and Community Medicine, University of New SouthWales, Sydney, Australia2Cancer Institute NSW, PO Box 41, Alexandria, NSW 1435, Australia

White et al. BMC Public Health (2019) 19:296 https://doi.org/10.1186/s12889-019-6633-4

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only 44% of gynaecologic surgeons in Ontario adheringto guidelines for surgical staging [3].Whilst clinical variations are to be expected and are

not always problematic, they have attracted increasinginterest in health systems internationally as a mechanismfor understanding the quality and appropriateness ofcare provided to patients, highlighting quality featuressuch as efficient, effective and timely care [6]. The domin-ant conceptual framework and related theory is that setout by Wennberg and colleagues. Wennberg’s classifica-tion of variation identifies three categories that can beused to identify when clinical care variation is unwar-ranted: effective care, preference sensitive care and supplysensitive care [7, 8]. The category of effective care identi-fies those services and procedures that have been proveneffective in the research literature for all patients. Clinicalvariation related to effective care is often conceptualisedthrough deviation from clinical guidelines.In ovarian cancer care there are a number of international

guidelines that guide effective treatment internationally. TheNational Comprehensive Cancer Network (NCCN) in theUnited States initially developed a clinical practice guidelinefor ovarian cancer in 1996, since then providing regular evi-dence and consensus based updates, with the most recentguideline published in 2017 [9]. The National Institute forHealth and Care Excellence, initially set up in the UnitedKingdom (UK) in 1999 to reduce variation in the availabilityand quality of treatment and care in the National HealthService, developed a clinical guideline for clinical practice inovarian cancer in 2011 [10]. The European Society forMedical Oncology has also published clinical practice guide-lines on the management of newly diagnosed and relapsedovarian cancer [11]. There have been recent developmentsin peri and intra operative surgical care with the develop-ment and implementation of Enhanced Recovery AfterSurgery Guidelines across a number of surgical areas, in-cluding gynaecologic oncology procedures [12, 13].To date, there has been no synthesis of evidence regard-

ing the degree of unwarranted clinical variation (deviationfrom effective care) in ovarian cancer care. Data regardingthe effectiveness of attempts to reduce unwarranted clinicalvariation in ovarian cancer care are also lacking. This re-view aims to address these knowledge gaps by providing asynthesis of evidence in relation to the following questions:(1) What is the evidence of guideline adherence in ovariancancer and its deviation?; (2) What are the key factors asso-ciated with variation in guideline adherence in ovarian can-cer care?; (3) What quality improvement approaches beenused and what is the evidence of their effectiveness in en-hancing guideline adherence in ovarian cancer care?

MethodsThis review was conducted and reported in accordancewith the Preferred Reporting Items for Systematic Reviews

and Meta-Analysis guidelines [14]. In this study we havedefined safe care using Wennberg’s effective care categoryas rationale for focusing on guideline adherent care andthe deviation from these [8].

Eligibility criteriaPublished journal articles reporting studies of any design,including literature reviews, were eligible for the study ifthey were available in English and published in the last11 years (2007 to November 2018). This timeframe waschosen to ensure the inclusion of journal articles rele-vant to contemporary healthcare. To be eligible, studieshad to focus on female adults (over the age of 18 years)who had received a diagnosis of primary ovarian, fallopiantube or peritoneal cancer. To be included, the reportedoutcomes had to focus on guideline adherence and itsdeviation, the key factors associated with variation inguideline adherence and what quality improvement ap-proaches have been used and evidence of their effective-ness. Conference abstracts, editorials, commentaries andgrey literature were excluded. Studies focussed on thecentralisation of ovarian cancer care have been definedfor the purpose of this review as effective care, usingWennberg’s classification of variation [7, 8]. These studieshave been reported on in a previous Cochrane review andhave been excluded as out of scope for this study [15].

Data sourcesKeywords and synonyms for the major concepts of ovar-ian cancer, clinical variation and guideline adherencewere developed and combined to form the search strat-egy. Systematic searches of MEDLINE, EMBASE, SCO-PUS and web of science were completed for publicationsbetween January 2007 to November 2018. Results weremerged using reference management software (endnote;Thomson Reuters), with duplicates removed. The searchstrategy has been included in Additional file 1. Thesearch terms used in the Medline database search were:Ovarian cancer, ovarian neoplasms, patterns of care,guideline or guideline adherence, variation of care, clin-ical variation, referral and consultation, referral pathway,optimal care, and framework. The terms framework andguideline were removed for search in web of science andSCOPUS due to the volume of material returned. Refer-ence lists were also scanned to identify additional rele-vant studies

Study selection and data extractionOne author (KW) screened the titles and abstracts of theextracted papers, identifying papers that met the inclu-sion criteria. A random sample of the papers (10%) werescreened by a second author (RH) who independentlyapplied the inclusion criteria. The same process wasfollowed for the full text review. Disagreements were

White et al. BMC Public Health (2019) 19:296 of 13

resolved through consensus. The following data were ex-tracted from the studies that met the inclusion criteria:author(s), date, method, data source, country, setting, sam-ple/participants, objective, main findings and limitations.

Data analysisData were synthesised using a narrative synthesis ap-proach [16]. This approach was chosen to allow for atext based analysis across the diverse range of researchand research approaches identified in this study. Theelements of narrative synthesis include developing atheory in light of the findings from the studies, developinga preliminary synthesis, exploring relationships within andbetween studies, and assessing the robustness of the syn-thesis [16].

ResultsA total of 2012 papers were identified during the search,after removing duplicates 1683 studies were left. Screeningof titles and abstracts found 41 studies that required fulltext review, with 32 studies meeting the inclusion criteriafor inclusion in the final review. A flow diagram outliningthe results of the search strategy is provided in Fig. 1.

Excluded studiesOf the 1651 studies excluded, 185 were excluded due towrong study design, 28 were excluded due to focussingon cancer screening and 427 were excluded as they fo-cused on quality improvement broadly and did not specif-ically focus on guideline adherence and clinical variation.

Characteristics of the studies includedOf the 32 studies included in this analysis, 19 reportedretrospective population registry or local registry ana-lysis, seven reported retrospective medical record audits,four were literature reviews, one reported a survey withclinicians and the final study included both a literaturereview and medical record audit. There were no qualita-tive studies that met the inclusion criteria. The studieswere primarily from the United States (17 studies) andEurope (12 studies), with two from Canada, and onefrom South Korea.Using a narrative synthesis approach to analyse the 32

papers, three broad groupings of publications wereidentified: 1) adherence to and deviation from guidelines(11 studies which were local, national or international)[3, 17–26]; 2) factors impacting guideline adherence (12

Fig. 1 Flow diagram of selection process. Flow diagram outlining the selection process of studies found in the initial search and how studieswere excluded, leading to the final 32 studies included in the systematic review


studies) [27–38] and 3) quality improvement approaches(9 studies) [39–47].

Guideline adherence and deviationOf the 11 studies grouped under guideline adherenceand deviation, 8 utilised the NCCN ovarian cancerguidelines as the comparator guideline, with 3 usingtheir own local or national guidelines [3, 17–26]. Thesestudies collectively indicated variation in adherence toguidelines for both surgical staging and receipt ofchemotherapy. Bristow et al. reported that across allovarian cancer cases in the Californian Cancer Registry,NCCN adherence was 37.2% over a 7 year period [17].This compares to Phippen et al. who investigated NCCNguideline adherence in a low volume institute and re-ported that 85.4% of patients received NCCN guidelineadherent surgery over an 8 year period [23]. One of thekey factors distinguishing these studies was that in thePhippen et al. study all surgery was completed by gynae-cological oncologists, with surgeon type not reported inthe Bristow et al. study [17, 23]. Erickson et al. found ahigher rate of guideline adherent care, at 78.5%, in theirsingle institution only study [19]. This is in contrast to thepopulation study by Hodeib et al. using data from theCalifornian Cancer Registry, finding guideline adherenceof 24% [21]. See Table 1 for characteristics of the studiesincluded under guideline adherence and deviation.

Factors impacting guideline adherenceIndividual hospital and/or surgeon volume and their linkto improved outcomes has been identified for surgerythat is technically complex [48]. Hospital and/or surgeonvolume emerged as the primary factor associated withthe degree of guideline adherence identified in 11 of theincluded studies in this review that in turn was linked toovarian cancer outcomes. Eight of the 11 studies identifiedhigher volumes with improved outcomes at a nationalpopulation level, with three studies focussing on highervolume leading to improved outcomes at a state or spe-cific geographical level [27–32, 34–36, 38]. Survival atboth 5-years and 4-years was found to be better forwomen treated in higher volume hospitals [29, 30, 32, 38].The Marth et al. and Bristow et al. studies found hospitalvolume was an independent predictor of survival [29, 36].Hospital volume was also found to be a statistically signifi-cant and independent predictor of optimal cytoreductivesurgery, i.e. guideline adherent care [28, 29]. Shakeel et al.and Wright et al. reported that higher volume hospitalshad lower in-hospital mortality and morbidity [33, 34].The study by Uppal et al. investigated the use of 30-dayreadmission following cytoreductive surgery as a measureof quality [49]. This study found that although higher vol-ume hospitals had higher rates of 30-day readmission,they also had higher rates of guideline adherent care and

an improved 5-year survival when compared to lower vol-ume hospitals with lower 30-day readmission rates [37].This supports their proposal that 30-day readmission fol-lowing ovarian cancer surgery is not a robust measure ofquality care. Overall the studies found that improvementin guideline adherence was associated with improved out-comes in hospitals where there was high volume ovariancancer care at a hospital and/or surgeon level. See Table 1for characteristics of the studies included under factorsimpacting guideline adherence.

Quality improvement approachesThere were nine studies identified investigating qualityimprovement approaches that attempted to detect, respondto or address clinical variations. Five of the studies focussedon the development of quality indicators for guideline ad-herent care as a way to identify variation in clinical practiceand improve outcomes [40, 44–47]. Three studies reportedon the impact of quality improvement programs on im-proving outcomes in ovarian cancer through increasingadherence to clinical guidelines, resulting in a reduction ofunwarranted clinical variation [39, 41, 42]. The final studyreported on one hospital’s compliance with Society ofGynecologic Oncology quality indicators [43]. Five studiesreporting on the development of quality indicators all hadsimilarities in the indicators developed, with a focus onrates of complete surgical resection [40, 44–47]. Three ofthese studies focussed further on the type of surgeon andtheir surgical volume [40, 45, 47]. The study by Phillips etal. focussed on the importance of identifying the denomin-ator in advanced ovarian cancer studies and quality indica-tors, to ensure outcomes are able to be appropriatelyinterpreted and the ‘denominator effect’ is understood [44].Phillips et al. defined the denominator in their study as thetotal number of advanced ovarian cancer cases presentingor referred to the cancer centre [44]. This then allowedthem to understand the proportion of patients who re-ceived treatment and the cancer centres overall survivalrates for women with advanced ovarian cancer [44]. Thestudy by Aletti et al. found an increase in complete cytore-ductive surgery from 31 to 43% following the implementa-tion of a quality improvement program [39]. The qualityimprovement program implemented included comparisonof hospital results with the latest evidence, confidential sur-geon benchmarking, educational sessions for trainees onnew and complex surgical techniques and improving theavailability of experienced staff members to assist withcomplex surgical cases [39]. The study by Kommoss et al.found women with stage 1A-IIIA ovarian cancer had animprovement of 27 to 88.5% in complete cytoreductive sur-gery following the implementation of a quality improve-ment program [42]. Harter et al. further reported on thesame quality improvement program for women with laterstage disease, finding complete cytoreductive surgery rates


Table 1 Characteristics of included studies (n = 32)

Reference Date Method Sample Objective Main findings

Aletti et al. 2009 Retrospectivemedical record audit

All women diagnosedwith FIGO stage IIICprimary epithelial ovarianor tubal carcinoma fromJanuary 2000 toDecember 2003 andJanuary 2006 toDecember 2007

To evaluate the effectiveness of aquality improvement program onsurgical quality and the rates ofspecific procedures.

Data were analysed from a 3-year periodprior to the quality improvement (QI)program implementation, and a 3-yearperiod following the implementation.Complete debulking increased from 31%in the pre-QI program to 43% post QIprogram.

Aletti et al. 2017 Review of NCCNguidelines

NCCN guidelines andpreviously publishedquality indicators

To describe existing surgicalquality indicators for early andadvanced ovarian cancer inrelation to the recent NCCNguidelines.

No changes or additions recommendto the indicators. Highlighted theneed for the implementation ofquality control programs, with thefocus on improving surgical outcomesfor women with ovarian cancer.

Bristow et al. 2009 Retrospectivepopulation basedregistry analysis

Adult women whounderwent a surgicalprocedure for ovariancancer in Maryland, USA,from 1 July 2000 to 30June 2008

To investigate patterns ofprimary surgical care for ovariancancer in Maryland according tosurgeon and hospital volume.

Surgeon volume was defined as: low≤4 cases/yr., intermediate 5–9 cases/yr., high ≥10 cases/yr. Hospital volumewas defined as: low ≤9 cases/yr.,intermediate 10–19 cases/yr., high ≥20cases/yr. Annual surgeon volume wasstatistically significant for associationwith risk of in hospital death. Hospitalvolume was not found to bestatistically significant for associationwith in hospital death.


Adult women whounderwent a surgicalprocedure for ovariancancer in Maryland, USA,from 1 July 2000 to 30June 2009

To evaluate the impact ofsurgeon and hospital casevolume on in-hospital mortality,extent of surgery, length of stayand hospital cost of care.

Surgeon volume was defined as: low< 10 cases/yr., high ≥10 cases/yr.Hospital volume was defined as: low< 20 cases/yr., high ≥20 cases/yr.Surgery performed by a high volumesurgeon was associated with a 69%reduction in risk of in-hospital death.Surgery at a high volume hospital wasa significant and independent predictorof cytoreductive surgery.


Women over 18 yrs. withFIGO stage IIIc/IVepithelial ovarian cancerfrom 1996 to 2005 inthe USA

To examine and quantify theeffect of hospital procedurevolume on overall care andprocesses for women withepithelial ovarian cancer.

Hospital volume was defined as: low< 9 cases/yr., intermediate 9–20 cases/yr., high 21–35 cases/yr., very high >35 cases/yr. 5-year survival for patientstreated at hospitals completing < 21cases/yr. was significantly poorer than forthose treated at hospitals completing> 21 cases/yr.


Cases of epithelialovarian cancer reportedto the California CancerRegistry from January1999 to December 2006.

To validate NCCN ovarian cancerguideline adherence as a qualityprocess in California, USA.

37.2% of patients received NCCNguideline adherent care. Receipt ofnon-NCCN guideline based care led tomore than a 30% increase in ovariancancer related death.

Chan et al. 2008 Retrospectivepopulation basedregistry analysis

Women residing inNorthern Californiadiagnosed with stageIC/II primary invasiveepithelial ovarian cancerfrom 1 January 1994–31December 1996.

To investigate factors associatedwith women under 55 years ofage with early stage ovariancancer not receivingchemotherapy based onstandard treatment guidelines.

78.5% of patients with early stagedisease received adjuvant chemotherapy.Non-receipt of adjuvant chemotherapywas found to be more likely for those liv-ing in poor neighbourhoods, have lowgrade cancers and be less likely to haveseen a gynaecological oncologist.

Cliby et al. 2015 Retrospectivepopulation basedregistry analysis

Women with invasiveepithelial ovariancancer diagnosedbetween 1 January1998 and 31 December2008 in the USA

To evaluate the patterns ofovarian cancer care in the USAto define the influence of patientand institutional factors onoverall survival, including theindependent relationshipbetween volume and outcomes.

Annual hospital volume was ranked inquartiles: 1–7, 8–16, 17–28 and > 29cases/yr. 43% of patients receivedNCCN guideline adherent care. Non-receipt of NCCN guideline care wasassociated with worse overall survival(HR 1.4, 95% CI 1.36–1.45) with overallsurvival best in centres with > 29cases/yr. (HR 0.91, 95% CI 0.86–0.96).


Table 1 Characteristics of included studies (n = 32) (Continued)


Dodge et al. 2007 Survey Gynaecologistsperforming gynaecologicsurgery in Ontario

To quantify the gap betweencurrent practice in surgicalstaging of ovarian cancer withCanadian clinical practiceguidelines.

44.3% of participants indicated theywould complete surgical staging inline with the Canadian clinical practiceguidelines. 81% of gynaecologicaloncologist’s vs 41.5% of non-oncologists indicated they wouldcomplete optimal staging.

Erickson et al. 2014 Retrospectivemedical record audit

Women diagnosed withstage IC/II epithelialovarian cancer between2004 and 2009 treatedin University of Alabamahealth system

To examine the reasonspreventing patients fromreceiving NCCN guidelineadherent care.

78.5% of patients received NCCNguideline adherent care. All patientswere seen by a gynaecologicaloncologist, removing the bias ofphysician specialty. Most commonreason for not receiving NCCNguideline adherent care wascomorbidity.

Galvan-Turneret al.

2015 Retrospectivepopulation basedregistry analysis

Women with stage I-IVepithelial ovarian cancerdiagnosed in Californiabetween 1 January 1996and 31 December 2006

To evaluate the feasibility ofdeveloping an observed-to-expected (O/E) ratio of adher-ence to NCCN guidelines as arisk-adjusted hospital measure ofquality ovarian cancer care, corre-lated with disease specificsurvival.

Care at high O/E hospitals wasassociated with significantimprovement in ovarian cancerspecific survival when compared tointermediate O/E and low O/Ehospitals. It was found to be feasibleto develop a risk adjusted hospitalmeasure of quality.

Harter et al. 2011 Retrospective localquality assurancedatabase analysis

Women with stage IIB-IVovarian cancer whoreceived surgerybetween 1997 and 2008at HSK Hospital,Germany.

To improve the quality of surgery,specifically increase optimalcytoreduction, a qualitymanagement program wasintroduced in 2001. This studyreports the outcome of this qualitymanagement program in womenwith advanced ovarian cancer.

Complete resection rates increasedfrom 33 to 62%, with postoperativeresiduals ≤1 cm increased from 65 to86%, with residual disease > 1 cmdecreasing from 35 to 14%. There wasa significant improvement in overallsurvival from 26months (1997–2000),to 37 months (2001–2003), to 45months (2004–2008).

Hodeib et al. 2015 Retrospectivepopulation basedregistry analysis

Women with stage I/IIinvasive epithelialovarian cancerdiagnosed in Californiabetween 1 January 1996and 31 December 2006

To investigate the impact ofsocioeconomic status and otherdemographic variables onadherence to NCCN guidelines inpatients with stage I/II disease.

24% of patients received NCCNguideline adherent care. 16% ofpatients in the lower socioeconomicgroup received NCCN guidelineadherent care.

Ivanova et al. 2017 Retrospectivepopulation basedregistry analysis

Women in Bulgaria withovarian cancer diagnosedfrom 2009 to 2011

To investigate if low hospitalvolume contributes to thenumber of cases withunspecified morphologiccharacteristics, which has beenassumed as a possible indicatorof suboptimal care.

Hospital volume was defined as: low< 30 cases/yr., high ≥30 cases/yr. 53%of patients were treated in lowvolume hospitals. Low volume vs highvolume hospitals had higher numberof cases with unspecified grade (27.7%vs 14.3%) and unspecified stage(37.9% vs 27.4%).

Kommoss et al. 2009 Retrospective andprospective localinstitution clinicaltumour registryanalysis

Women with stage IA-IIIA ovarian cancer whoreceived surgery be-tween 1997 and 2007 atHSK Hospital, Germany.

To improve the quality of surgery,specifically increase optimalcytoreduction, a qualitymanagement program wasintroduced in 2001. This studyreports the outcome of thisquality management program inwomen with early ovarian cancer.

Women receiving standard surgeryincreased from 27 to 88.5% followingthe implementation of the qualitymanagement program.

Lee et al. 2015 Retrospectivemedical record audit

Patients with stage Iepithelial ovarian cancertreated surgically fromJanuary 1991 to December2010 at Seoul NationalUniversity Hospital

To evaluate the effects of NCCNguideline adherence on survivaloutcomes in early stage epithelialovarian cancer.

Guideline adherent surgical stagingwas completed in 26.7% of patients, ofthese 100% received guidelineadherent chemotherapy. Difference indisease-specific survival between thetwo groups was not statistically signifi-cant. Recurrence-free survival showeda statistically significant improvementin the guideline-adherent group.




Liang et al. 2015 Retrospectivemedical record audit

Consecutive patientswho underwent primarysurgical staging/cytoreduction forovarian cancer by 6gynaecologic oncologyproviders at the OhioState University fromJanuary 2010 andDecember 2012.

To evaluate compliance at asingle National Cancer Institute-designated ComprehensiveCancer Centre with the 8 ovariancancer quality indicatorsproposed by the Society ofGynaecology.

60% of patients were completelystaged, with lymphadenectomy beingthe most frequently omitted stagingprocedure. Bilateral para-aortic lymphnode dissection was excluded in23.6% and bilateral pelvic lymph nodedissection excluded in 18.2% of stageI-IIIB cases. 51.8% of optimallydebulked stage III patients receivedintra-peritoneal chemotherapy within42 days of cytoreduction. Of note,there were documented reasons fordecision not to proceed with intra-peritoneal chemotherapy in all but 2cases. Compliance was reasonable forthe other quality indicators.

Mandato et al 2013 Retrospectivemedical record audit

All patients with adiagnosis of epithelialovarian cancer in Emilia-Romagna Hospitals, Italy,from 2007 to 2010

To investigate the managementand treatment of epithelialovarian cancer in Emilia-RomagnaHospitals.

Hospital volume was defined as: low≤10 cases/yr., medium 11–20 cases/yr.and high ≥21 cases/yr. 46% ofpatients were treated in a highvolume hospital. Completecytoreduction was achieved in 20.1%of patients with stage III-IV disease. Pa-tients treated in high volume hospitalspresented a significantly lower risk ofdying compared to patients treated inmedium and low volume hospitals.

Marth et al. 2009 Retrospectivepopulation basedregistry analysis

Women with ovariancancer treated in Austriafrom 1999 to 2004 fromparticipating Austriangynaecologicaldepartments.

To evaluate factors predictingoverall survival, with considerationof department volume.

Hospital department volume wasdefined as: small ≤23 patients/yr.,large ≥24 patients/yr. Survival waslonger at large vs small departments,5-year survival of 69% vs 61% (p =0.01). Department size was found tobe an independent predictor ofsurvival (HR 1.39 for treatment insmall departments).

Phillips et al. 2017 Retrospectivemedical record auditand literature review

Patients diagnosed withstage III/IV advancedovarian cancer from 16August 2007 to 3February 2014 at thePan-Birmingham Gynae-cological Cancer Centre,UK.

To evaluate the effect of thedenominator on survival of thetotal advanced ovarian cancercases identified through asystematic literature, as well asdata from the Pan-BirminghamGynaecological Cancer Centre,UK.

Reporting the denominator in studiesin advanced ovarian cancer isimportant to correctly interpret theoutcomes being reported. Of the 18studies identified, 2 reported on theirtotal patient cohort, with no studiesreporting overall survival for their totalpatient cohort. Data from the medicalrecord audit demonstrated decreasingoverall survival as treatment becameless aggressive. Median overall survivalfor the total patient cohort was 30.2months.

Phippen et al. 2013 Retrospectivemedical record audit

Patients diagnosed withepithelial ovarian cancer,fallopian tube cancer, orprimary peritonealcancer between 2002and 2010 at BrookeArmy Medical Centre.

To evaluate the optimalcytoreduction rate, NCCNguideline adherence rate andsurgical outcomes at a lowvolume institution.

85.4% of patients received NCCNguideline adherent surgery.Compliance rate in line with reportsfrom high volume centres from thislow volume centre.

Querleu et al. 2013 Literature review andexpert consensus

Development of qualityindicators based onstandards of practiceand expert consensus.

Development of qualityindicators for France by theFrench Society of GynaecologicOncology.

Three structural, eight process andtwo outcome quality indicators weredeveloped. The paper highlighted theneed to implement the indicatorsthrough a quality assurance programand pose that their implementationwould result in a positive impact insurvival for women with ovariancancer in France.




Querleu et al. 2016 Literature review andexpert consensus

5 initiatives publishingquality indicators foradvanced ovarian cancersurgery were identified.A multidisciplinaryInternationalDevelopment Groupwas established todevelop the qualityindicators.

To develop quality indicators foradvanced ovarian cancer surgery,carried out by the EuropeanSociety of GynaecologicOncology (ESGO).

10 quality indicators were developedthrough this evidence based andconsensus process. The indicators arecategorised as structural, process oroutcome. ESGO aims to implementtheir quality assurance program foradvanced ovarian cancer using theseindicators, with achievement targetsapplied to each indicator.

Shakeel et al. 2017 Retrospectivepopulation basedregistry analysis

Women with anovarian cancerdiagnosis in Canada(excluding Quebec)from 2004 to 2012.

To evaluate the quality ofsurgical care for women withovarian cancer in Canada byassessing surgical volume andsurgeon speciality on short-termpostoperative outcomes.

Hospital volume was defined as: low1–27 procedures/yr., intermediate 29–28 procedures/yr., high 99–201procedures/yr. Surgeon volume wasdefined as: low 1–4 procedures/yr.,intermediate 5–23, high 24–57procedures/yr. In-hospital mortalityrate in 2004 was 1.3%, declining to0.74% in 2012. Increasing age andcomorbidity were significant predictorsof in-hospital mortality. Hospital surgicalvolume was a significant predictor of re-duced risk of in-hospital mortality andfailure-to-rescue, but longer length ofstay. Surgeon volume significantlypredicted an increased risk of majorcomplications and prolonged length ofstay. Ovarian cancer surgery in Canadais performed by a large number ofsurgeons with low surgical volume/yr.

Sijmons et al. 2007 Retrospectivemedical record audit

Women diagnosedbetween 1991 and 1997with stage IA, IB or ICovarian cancer in thecentral region of theNetherlands.

To assess compliance withcurrent surgical staging andadjuvant local treatmentguidelines and overall survival forpatients with early stageepithelial ovarian cancer.

32.8% of patients received optimalsurgical staging, chemotherapyguidelines were followed in 100% ofgrade 1, and 74.6% of grade II and IIIpatients. 5-year overall survival in theoptimally staged cohort was 97.6, and68.5% in the non-optimally stagedcohort.

Sobrero et al. 2016 Retrospectivemedical record audit

Residents of thePiedmont Region of Italydiagnosed with ovariancancer in 2009

To investigate whether ovariancancer in the Piedmont Region isbeing managed according tocurrent local, evidence-basedclinical guideline; to identifydeterminants of lack ofadherence to guidelines; and toevaluate the association betweenadherence to clinical guidelinesand survival.

35.2% of patients received guidelineadherent surgery, with 87.8% ofpatients receiving guideline adherentchemotherapy. Receipt of guidelineadherent chemotherapy wasassociated with a significant reductionin all-cause mortality (HR, 0.5; 95%CI,0.28–0.89)

Uppal et al. 2018 Retrospectivepopulation basedregistry analysis

Women with a diagnosisof high-grade serousovarian carcinomaundergoing primarycytoreductive surgeryfrom 2004 to 2013.

To evaluate the role of 30-dayreadmission rate as an indicatorof quality of care in ovariancancer surgery.

Hospital case volume was defined as:≤ 10 cases/yr., 11–20 cases/yr., 21–30cases/yr., > 31 cases/yr. Higher volumehospitals had higher 30-day readmissionrates, but had significantly lower 30 (OR0.69, 95%CI 0.50–0.96) and 90-daymortality (OR 0.74, 95%CI 0.60–0.91).Higher volume hospitals had higherre-admission rates, but also had higherNCCN guideline adherence, and improve5-year overall survival.

Verleye et al. 2009 Literature review andexpert consensus

The PUBMED databasewas searched, withjournal papers as well asguidelines andstandards of carereviewed. Details of the

To develop a list of processquality indicators for staginglaparotomy in stage I-IIIA ovariancancer, and debulking laparot-omy in stage IIIB-IV ovarian can-cer for the European

5 indicators were proposed for staginglaparotomy (stage I-IIIA), with 6 indicatorsproposed for debulking surgery (stageIIIB-IV). These proposed indicators willneed to be evaluated for feasibility,validity and reliability.


for women with stage IIB-IV ovarian cancer improved from33 to 62%, with overall survival improving from 26monthsto 45months following the implementation of the qualityimprovement program [41]. The quality improvement pro-gram reported on in the Kommoss et al. and Harter et al.studies focussed on optimal surgical staging, receipt of plat-inum based chemotherapy, surgeon volume and experi-ence, as well as the implementation of dedicated ovariancancer surgical teams, benchmarking of morbidity and

outcomes, and improvement of interdisciplinary assessmentand management [41, 42]. There are commonalitiesbetween the three studies that reported on outcomes ofthe implementation of quality improvement programs,including adherence to guideline based care, improvementin ongoing surgical education and surgeon benchmarking[40–42]. The study by Liang et al. found high clinical vari-ation in the indicators of complete surgical staging andthe administration of intraperitoneal chemotherapy within



search results were notreported.

Organisation for Research andTreatment of Cancer (EORTC-GCG).

Warren et al. 2017 Retrospectivepopulation basedregistry analysis

Women in the USAdiagnosed with ovariancancer in 2002 and 2011

To evaluate population basedtrends in ovarian cancertreatment and survival, with afocus on NCCN guidelineadherent care, assessing patientand provider characteristics andestimating trends in 2-yearcause-specific survival.

In stage II ovarian cancer the percentof women who received guidelineadherent surgery increased from18.3% in 2002 to 31.7% in 2011, instage II from 48.9% in 2002 to 56.7%in 2011, with stage IV remaining stableat 34% for the two time periods.Receipt of guideline adherentchemotherapy rose significantly overthe time period, with at least 70% ofwomen receiving multiagentchemotherapy in 2011.

Wright et al. 2013 Retrospectivepopulation basedregistry analysis

Women in the USA aged65 years or older withovarian or uterine cancerwho underwent surgeryfrom 2000 to 2007.

To estimate trends in hospitalvolume and referral patterns forwomen with uterine and ovariancancer.

The median hospital volume remainedconstant throughout the study periodat 2 cases per 2 years. During thestudy period there was marketconcentration, where a similar numberof patients undergo the procedureover time, with the number ofhospitals decreasing, with increasingnumber of procedures beingcompleted in higher volume hospitals.Overall, women with gynaecologiccancers continue to be treated at verylow volume centres.

Wright et al. 2012 Retrospectivepopulation basedregistry analysis

Women in the USAaged 18–90 with ovariancancer and underwentoophorectomy from1998 to 2009.

To examine the influence offailure to rescue as a source ofvariation in mortality for patientswith ovarian cancer.

Hospital volume was defined as: low1–36 procedures/yr., intermediate36.1–53 procedures/yr., high > 53procedures per year. The overallcomplication rate was 22.8%, with thefailure to rescue rate being 6.2%,decreasing from 8.7% in 1998 to 6% in2009. The adjusted failure to rescuerate was 48% higher at low comparedto high volume hospitals.

Wright et al 2017 Retrospectivepopulation basedregistry analysis

Women in the USAdiagnosed with invasiveepithelial ovarian cancerfrom 2004 to 2013

To examine if is lower volumehospitals that comply with NCCNquality metrics can achieveoutcomes similar to high volumehospitals.

Five quality metrics were definedbased on NCCN guidelines, withadherence to the metrics identified,reported on and aligned to hospitalvolume. Compliance with the qualitymetrics increased with hospitalvolume. For each volume category 2-year adjusted survival increased withadherence to the quality metrics, from61.4% in the low volume with lowquality metric compliance hospitals to78.6% at the highest volume and highquality metric compliance hospitals.


42 days of optimal cytoreductive surgery [43]. See Table 1for characteristics of the studies included under qualityimprovement approaches.

DiscussionThis review completed a synthesis of the evidence in re-lation to the degree of unwarranted clinical variation forwomen with ovarian cancer and the effectiveness of at-tempts to improve clinical variation. Findings from the32 included studies were extracted in relation to threekey areas: adherence to and deviation from guidelines,factors impacting guideline adherence, and quality im-provement approaches to reduce variation through en-hanced guideline adherence. Despite strong evidence ofthe optimal care process for ovarian cancer, aligning withWennberg’s classification of effective care, variation wasapparent in the extent to which guideline adherent carewas practiced for women with ovarian cancer internation-ally [8]. Commonalities between the studies includednon-adherence to guidelines in surgical staging, optimalcytoreductive surgery and receipt of adjuvant chemother-apy [3, 16–24]. Variation in guideline adherent care, andspecifically deviation from effective care, is likely to lead tounwarranted clinical variation in outcomes for ovariancancer patients. Quality improvement approaches such asthe use of quality indicators and team-based quality im-provement projects have been utilised to reduce unwar-ranted clinical variation, with some evidence of success.The most successful quality improvement approachesfound in this review focused on the development ofquality improvement programs across gynaecologicaloncology services. These successes facilitated clinicalchange through the implementation of dedicated ovariancancer surgical teams, education on new and emergingsurgical techniques and benchmarking at a hospital andsurgeon level [38, 40, 41].Surgical volume at both a hospital and surgeon level

have been associated with improved outcomes in ovariancancer for many years, with the study by Luft et al. in1979 being one of the earliest studies to identify thisassociation [48]. The association between improved sur-gical outcomes and high hospital or surgeon volume hasbeen identified in a number of cancer types that requiretechnically complex surgery, such as pancreatectomy[48, 50]. One of the key factors in the relationship be-tween volume and care outcomes is thought to be theincreased likelihood of those practicing high volume careto adhere to best practice guidelines. Our findings identifiedevidence to support the relationship between hospital vol-ume, surgeon volume, guideline adherence and outcomesin ovarian cancer care such that higher volume hospitalsand surgeons were found to be independently associatedwith increased survival, as well as increased levels of guide-line adherent care [27–36]. Guideline adherent surgery in

ovarian cancer includes complex surgical techniques that aspecialist surgeon, such as a gynaecological oncologist, mayonly achieve competency in though completing a high vol-ume of these surgeries, with the support of a specialistmultidisciplinary team in their hospital [15, 29].A key finding of this review is that the implementation

of quality indicators through a formal quality improvementprogram has led to improvements in guideline adherentcare, as highlighted in the improvement of complete cytore-ductive surgery in the studies by Aletti et al., Kommoss etal. and Harter et al. [39, 41, 42]. While the development ofquality indicators is a key part in this process, the in-cluded studies highlighted improvements in clinicalvariation that can be achieved when indicators are im-plemented into clinical practice. Three of the studiesoutlined the process of developing quality indicators atnational and international levels [45–47]. However, thefour studies that reported on the implementation ofquality indicators through quality improvement programswere implemented in single institutions [39, 41–43]. Thesestudies demonstrated that improvements in guideline ad-herent care could be made, with only one study reportingon an improvement in overall survival [41].

ImplicationsGiven the relationship between hospital and surgical vol-ume, guideline adherence and care outcomes, our findingssuggest that there is value in programs to promote guide-line adherent care in hospitals with high surgical volume, atboth a hospital and surgeon level [30, 33]. Developmentand implementation of quality indicators and quality im-provement programs to improve ovarian cancer outcomeshave been used internationally in an attempt to reduceunwarranted clinical variation in ovarian cancer care[39–43, 45–47]. A core strategy associated with suchprograms is the centralisation of care to hospitals thathave specialist gynaecological oncology centres andcomplete a high volume of ovarian cancer surgery atboth the hospital and surgeon annually [51–54]. Evi-dence suggests that centralising ovarian cancer careinto specialist hospitals improves access to gynaeco-logical oncologists, multidisciplinary cancer care teamsand higher surgical volume hospitals and surgeons maylead to improved survival [15].The development of gynaecological oncology as a surgi-

cal sub-speciality in Australia, the UK and North Americahas led to increasing specialist care in the treatment of gy-naecological cancer. In a study identifying practice guide-line adherence in Ontario, Canada, 81% of gynaecologicaloncologists reported completing surgical staging adherentto guidelines, with only 41.5% of non-oncologists complet-ing guideline adherent surgical staging [3]. A study byChan et al. found treatment by a gynaecological oncologistled to more women in California to undergo primary


staging surgery (91.9% vs. 69.1%) and chemotherapy (90%vs. 70.1%) than those treated by a non-oncologist [55].An important focus for future research is to establish

evidence of the effectiveness of the implementation ofquality improvement programs, reporting on survivalover time. Evidence of the relationship between qualityimprovement programs and survival is important forassessing the impact of implementing quality indicatorsthrough quality improvement programs as a way to de-crease unwarranted clinical variation and improve out-comes for women living with ovarian cancer. Analysis ofthe implementation of quality indicator and quality im-provement programs across regional or national jurisdic-tions that aim to improve outcomes in ovarian cancerbeyond a single institution level would be valuable.

LimitationsThe included studies and review process were subject tosome limitations. Whilst hospital and surgeon volumewere identified as important, a key challenge for inter-preting the results of these studies was the range of casevolume for hospitals, with each study defining volume indifferent ways. High hospital volume ranged from > 20to > 30 cases/yr. [29–32, 36]. High surgeon volume wasmore consistent, being identified as ≥10 cases/yr. in thetwo studies by Bristow et al. that investigated surgeonlevel volume [27, 28]. For health systems undertakingcentralisation of ovarian cancer surgery this may lead tochallenges in identifying which hospitals should be com-pleting ovarian cancer surgery. Reliance on administra-tive datasets created limitations such as selection bias, asmost registries did not cover the entire population, witha lack of information on stage of disease, extent of cytor-eductive surgery and surgeon specialist type. Two exam-ples are the study by Erickson et al. as a single institutestudy finding a high rate of guideline adherent care, at78.5%, and the study by Hodeib et al. which used popu-lation data and found a low rate of guideline adherentcare at 24% [19, 21]. A limitation in study design, usingsingle institution versus population data, may in someway explain the vast difference in guideline adherencebetween the two studies [19, 21]. The review processmay have omitted relevant material by including onlystudies published in English, the exclusion of studies al-located to broader quality of care issues, as there aremany factors associated with clinical variation, guidelineadherence being just one, and the date range of the past11 years.

ConclusionThis review has reported for the first time exploringguideline adherence and the factors impacting on thistowards clinical variation in ovarian cancer, highlightingguideline adherence and deviation, factors impacting

guideline adherence, and quality improvement approaches.There is evidence of deviation from effective care in ovariancancer, demonstrated through deviation from best practiceguidelines. Such deviation is likely to lead to unwarrantedclinical variation in ovarian cancer care. Centralising care tohigher volume centres and surgeons, and the growth ofgynaecologic oncology as a specialty appear to be associatedwith enhanced guideline adherence, reduced variation andbetter outcomes as a result. The development, implementa-tion and reporting of quality performance programs mayalso lead to reduced unwarranted variation in ovarian can-cer care, but evidence is currently limited regarding theeffectiveness of these programs at regional and nationallevels and on longer term outcomes.

Additional file

Additional file 1: Search terms. Overview of the search terms used forthe four database searches. (DOCX 16 kb)

AbbreviationsNCCN: National Comprehensive Cancer Network; UK: United Kingdom

AcknowledgementsNot applicable

FundingThis research was supported by an Australian Government Research TrainingProgram Scholarship.

Availability of data and materialsThe search terms used in this systematic review have been made available inAdditional file 1.

Authors’ contributionsKW designed the study, led the search, primary analysis and manuscriptdevelopment. RH and HS assisted in the study design, analysis and manuscriptdevelopment. All authors read and approved the final manuscript.

Ethics approval and consent to participateEthics approval was not required for this systematic review.

Consent for publicationNot applicable

Competing interestsThe authors declare they have no competing interests.

Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.

Received: 10 December 2018 Accepted: 6 March 2019

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