Recommendations for the surgical management of gynecological cancers during the COVID-19 pandemic - FRANCOGYN group for the CNGOF.

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Guidelines

for

clinical

practice

Recommendations

for

the

surgical

management

of

gynecological

cancers

during

the

COVID-19

pandemic

-

FRANCOGYN

group

for

the

CNGOF

$

ARTICLE INFO Articlehistory:

Availableonline1April2020

Keywords: Gynaecologicalcancer COVID-19 Guideline Management ABSTRACT

Introduction:InthecontextoftheCOVID-19pandemic,speciﬁcrecommendationsarerequiredforthe managementofpatientswithgynecologiccancer.

Materials andmethod:TheFRANCOGYN groupoftheNationalCollege ofFrenchGynecologistsand Obstetricians (CNGOF)convenedtodeveloprecommendations basedon theconsensusconference model.

Results:IfapatientwithagynecologiccancerpresentswithCOVID-19,surgicalmanagementshouldbe postponedforatleast15days.Forcervicalcancer,radiotherapyandconcomitantradiochemotherapy couldreplacesurgeryasﬁrst-linetreatmentandthevalueoflymphnodestagingshouldbereviewedona case-by-casebasis.Foradvancedovariancancers,neoadjuvantchemotherapyshouldbepreferredover primary cytoreduction surgery. It is legitimate not to perform hyperthermic intraperitoneal chemotherapy duringtheCOVID-19pandemic.Forpatientswhoare scheduledtoundergointerval surgery,chemotherapycanbecontinuedandsurgeryperformedafter6cycles.Forpatientswithearly stageendometrialcanceroflowandintermediatepreoperativeESMOrisk,hysterectomywithbilateral adnexectomy combined with a sentinel lymph node procedure is recommended. Surgerycan be postponedfor1–2months in low-riskendometrial cancers(FIGO Iastage onMRIand grade1–2 endometrioid canceronendometrialbiopsy).ForpatientsofhighESMOrisk,theMSKCCalgorithm (combiningPET-CTandsentinellymphnodebiopsy)shouldbeappliedtoavoidpelvicandlumbar-aortic lymphadenectomy.

Conclusion:DuringtheCOVID-19pandemic,managementofapatientwithcancershouldbeadaptedto limittherisksassociatedwiththeviruswithoutincurringlossofchance.

Theserecommendationsarebasedoncurrentknowledgebut mayevolveasnewdataemerges.

In the current pandemic context of COVID-19 and the subsequentsaturationofresuscitationservices,overthenext2– 3monthswemustnotonlyreconsiderourtherapeuticindications butalsolimittheriskofinfectioninourcancerpatients.Toreduce theriskofinfectionstwoprioritiesarecrucial:tolimithighrisk situations suchas surgery and chemotherapy;and to limit the patient’scontactwithhealthcareworkersand,inparticular,with placesofcare.

Whilebearinginmindthatthemainobjectiveforourpatients withpelvicgynecologiccancerremainstherapeuticmanagement, allalternativestosurgerymustbeconsidered.Inparticular, the risk-beneﬁt ratiofor surgicalproceduresmustbeanalyzedona case-by-casebasisand inmultidisciplinarymeeting,taking into

account the risk of loss of chance that could result from an alternativestrategythathasnotbeenproven.Themainobjectiveis to avoidpostoperative complications and theneed for ensuing postoperativeintensivecareandinparticulartheoccupationofa resuscitationbed.However,inasfarasitispossibleaccordingto thesaturationof thestructureofcarerelatedtoCOVID-19,it is advisabletoapplytraditionalrecommendations.

IfapatientpresentswithCOVID-19,surgicalmanagementand allotheroncologicaltreatmentshouldbepostponedforatleast15 days.

Cancer patients are4–8 times more likely than thegeneral populationtodevelopsevererespiratorycomplicationsrelatedto COVID-19markedbyrapidonsetandoftenfataloutcome.Therisk ismoreacuteiftheyhaveundergonesurgeryorchemotherapyin theprecedingweeks.Thesepatients’vitalprognosisisatriskin additiontotherisklinkedtocancer.Theyshouldbeprovidedwith amaskandusehandsanitizersonarrivalatthehospital.

Preamble

Managementoftheoncologypatientisconventionallybasedon twostrategies:

$ _Groupe _FRANCOGYN _(Groupe _de _Recherche _en _chirurgie _Oncologique _et Gynécologique),GroupeD’intérêtduCNGOF(CollègeNationaldesGynécologues ObstétriciensFrançais).91,boulevarddeSébastopol.75002P.

http://dx.doi.org/10.1016/j.jogoh.2020.101729

JournalofGynecologyObstetricsandHumanReproduction49(2020)101729

Available

online

at

ScienceDirect

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1)Curative: for localized diseases, or for certain advanced / metastaticcancerscharacterizedbyaparticularsensitivityto treatmentsoradiseasecoursewhichmakesthemcurableby medical,surgicalorradiotherapeutictreatment

2)Palliative (non-curative): for diseases too advanced to be curable.

InthecurrentCOVID-19context,patientprioritizationshould integratethenatureofthetherapeuticstrategy(curativeversus palliative),theirage,estimatedlifeexpectancy,andwhetherthe diagnosisisrecentornot.

Takingintoaccount thedurationof incubationand thehigh percentage of asymptomatic patients, all pathologic samples shouldbeconsideredaspotentiallyinfected.Arecentpublication hasshownthatﬁxationinformalincaninactivatetheCOVID-19 virus.Theriskoftoxicitylinkedtoformalinexposureappearstobe lessseriousthanthatlinkedtothehandlingoffresh,non-ﬁxed tissue potentially carrying COVID-19. If necessary, operating samplesfrompatientsincludedinclinicaltrialscanbesentfresh to the laboratory but all the necessary precautions should be applied.

Imagingtestsshouldbemaintainedorpostponedaccordingto their importance and the impact on the choice of treatment strategy.

1.Allmultidisciplinarymeetings

Allmultidisciplinarymeetingsshouldbeorganizedfollowing the recommendations of the ONCORIF group (https://www.

oncorif.fr/2020/03/coronavirus-recommandations-et-contenus-ﬁables/).Asfaraspossible,multidisciplinarymeetingsshouldbe

heldwithatripleobjective:nottodelaythecareofpatientswho need it; not to unnecessarily mobilize doctors who are not absolutely necessary for the discussion; not to promote the transmissionofthevirusbetweencardiopulmonaryresuscitation (CPR) doctors. It is strongly advised to hold dematerialized meetingswhenpossiblebasedonvideoorteleconferencingeven ifthedoctorspracticeinthesameestablishment.

2.Weproposethefollowingadaptationsforthemanagementof patientswithgynecologicpelviccancerduringtheCOVID-19 pandemicperiod

2.1.Forcervicalcancer

Radiotherapy and concomitant radiochemotherapy should replace surgery as ﬁrst-line treatment whenever possible. In particular, the value of lymph node staging surgeries must be reviewedonacase-by-casebasisdependingonthesite,theresults of imaging tests and the disease stage. Hysterectomy after concomitant radiochmotherapy is only indicated if a post-therapeutictumorresidueisidentiﬁed.

2.2.Forovariancancer

Foradvancedcancerswhichmayrequiretheuseof postopera-tiveresuscitationforcytoreductionsurgery,neoadjuvant chemo-therapy should be the preferred option even if primary cytoreductionsurgerycouldbeenvisaged.Itislegitimatenotto offer hyperthermic intraperitoneal chemotherapy (HIPEC) to patientsduringtheCOVID-19pandemicperiodwhenresuscitation resources are saturated. If access to the operating theater is restrictedduetothecrisis,patientsscheduledtoundergointerval surgeryafter3or4cyclesofchemotherapycouldcontinuetheir chemotherapy and surgery be performed after 6 cycles of chemotherapy. The patient should then undergo at least two

new cycles of chemotherapy after their closing surgery (in agreement with INCa recommendations https://www.e-cancer.

fr/Expertises-et-publications/Catalogue-des-publications/Sum-mary-Initial-management-of-epithelial-ovarian-cancer-cases).

For presumed early stage ovarian cancers according to adnexectomy,restagingsurgerycanbedeferredfrom1–2months ifaccesstoanesthesia-resuscitationissaturated.

Furthermore, in case of saturation of access to anesthesia-resuscitation, a 2-step strategy is recommended for images suggestive of ovarian cancer on an isolated ovarian mass: adnexectomy of the suspect mass, and decision to perform completestagingsurgeryon_ﬁnalhistologicanalysisanddecision ofaCPRdoctor.

2.3.Forendometrialcancer Earlystagecancers

Surgicaltreatmentremainsthegoldstandardforearlystage endometrialcancer.Theminimallyinvasivelaparoscopic robot-assisted or non-assisted route is the preferred option. Total hysterectomy with bilateral adnexectomy associated with a sentinel node procedure should be performed in patients of lowand intermediate preoperativeESMO risk.Surgery can be postponedfor1–2monthsforlow-riskendometrialcancers(FIGO Ia stage on MRI and grade 1–2 endometrioid cancer on endometrial biopsy) if there is no element of discrepancy on theinitialassessment,especiallyifthepatientiselderlyand/or with comorbidities,without loss of oncological chance for the patient.

ForpatientsathighESMOriskaccordingtopelvicand lumbar-aortic lymphadenectomystaging, comorbidities and the terrain (obesity,anticoagulanttreatment,diabetes,age)shouldbetaken intoaccount.Inthiscontext,itwouldbelegitimatetoapplythe MSKCCalgorithm(associatingPETCTandGSprocedure)toavoid lymphadenectomywhichincreasestheriskofper-and postoper-ativecomplicationsandthesubsequentriskofrequiring postop-erativeresuscitation.

Foradvancedendometrialcancers(stagesIIIandIV),ﬁrst-line medicaltreatmentshouldbeadministered.

Forsuspectedendometrialcancer

Forapatientwhopresentspostmenopausalmetrorrhagiaand endometrial thickening on ultrasound, endometrial pipelle sampling should be performed in consultation. Diagnostic hysteroscopyinconsultationshouldbeavoidedunlessperformed atthe sametime(to limitthenumberofpatient trips). Inthe eventof a non-contributorydiagnosticassessment, thedateof the diagnostic hysteroscopy and biopsy curettage should be adjusted according to the degree of suspicion of endometrial cancerandtheconstraintsofaccesstotheoperatingroom.Ifthe risk of cancer appears low and the patient is elderly, the procedureundergeneralanesthesiacanbepostponeduntilafter theconﬁnementperiodforCOVID-19.

2.4.Forvulvarcancers

Themanagementofvulvarcancers,forwhichsurgeryremains the standard and often the only treatment option, should not change. However,this canceroften affects the elderlyand if a tumorhasnotprogressedmuchinanelderlypatient,treatment may be postponed for a few weeks. The patient should be dischargedasearlyaspossibleandcaredforathometoreducethe durationofhospitalization.

Whensurgicalmanagementinvolvesheavysurgery (amputa-tion), the use of concomitant radiochemotherapy should be discussedinCPR.

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2.5.Forvaginalcancer

Most patients presenting with vaginal cancer are at an advanced stage and will require exclusive radio- / chemo- / brachytherapytreatment.Thevalueoflymphnodestagingsurgery must be reviewed on a case-by-case basis depending on the location,theresultsofimagingtests,andthediseasestage. 2.6.Fortrophoblastictumors

Trophoblastictumors areconsideredcurablebuthaveahigh metastaticpotential.Thisjusti_ﬁesmaintainingthecareof these youngpatientswithoutdelay.

Patients with low risk trophoblastic tumors (FIGO score 6) shouldbeadministeredmethotrexateathometoavoidthefour injectionsofeachcureinanoutpatientsetting.

Patientswithhigh-risktumorsshouldbeadministered multi-drug regimens without delay given the generally multi-metastaticnaturefromtheoutset.

Finally,hydatidiformmolesshouldbemanagedbythestandard treatmentofcurettagesuctionunderultrasoundcontrolandnotby medicinalevacuationwhichcarriesahighriskofretention.

The French Reference Center for Trophoblastic Diseases is available for case-by-case discussion and can provide the treatment protocol with methotrexate at home if necessary (touria.hajri@chu-lyon.fr).

3.Post-therapeuticfollow-up

Post-therapeuticoncologicalfollow-upconsultationsshouldbe postponed for 2 months (i.e., after the COVID-19 conﬁnement period),becausethereisnoobviouslossofchance.Follow-upcan beperformed by teleconsultationwhen the technical toolsare available. However, follow-up of endometrial and / or cervical cancerisbasedonclinicalexamination,whichcannotbereplaced byteleconsultation,andavoidafollow-upconsultation2months later. CherifAkladiosa HenriAzaisb MarcosBallesterc SoﬁaneBendifallahd Pierre-AdrienBolzee NicolasBourdelf AlexandreBricouc GeoffroyCanlorbeb XavierCarcopinog PaulineChauvetf PierreCollineth CharlesCoutanti YohannDabid LudivineDionj TristanGauthierk OlivierGraesslinl CyrilleHuchonm MartinKoskasn FredericKridelkao VincentLavouej,_* LiseLecointrea MatthieuMezzadrip CamilleMimounp LobnaOuldamerq EmilieRaimondl CyrilToubould

a_Service_de_{gynécologie,}_CHU_de_Hautepierre,₆₇₀₀₀_Strasbourg,

France

b_Service_de_{gynécologie,}_Hopital_la_Pitié_Salpetriee,₇₅₀₁₃_Paris,

France

c_Service_de_{gynécologie,}_Dioconessess_Croix_Saint_Simon,₇₅₀₁₂_Paris,

France

d_Service_de_gynécologie_{obstétrique,}_{HôpitalTenon,}₇₅₀₂₀_Paris,

France

e_Service_de_gynécologie_{Obstétrique,}_CHU_Lyon_Sud,₆₉₀₀₀_Lyon,

France

f_Service_de_gynécologie_{obstétrique,}_Chu_Clermont_Ferrand,₆₃₀₀₀

ClermontFerrand,France

g

Servicedegyécologie,LaTimone,13000Marseille,France

h_Service_de_{gynécologie,}_Hôpital_Jeanne_de_Flandres,₅₉₀₀₀_Lille,

France

i_Centre_de_Lutte_Contre_le_Cancer,₂₁₀₀₀_Dijon,_France j_Service_de_{gynécologie,}_CHU_Hôpital_Sud,₃₅₀₀₀_Rennes,_France k_Service_de_gynécologie_{obstétrique,}_CHU,₈₇₀₀₀_Limoges,_France l_Service_de_gynécologie_{obstétrique,}_CHU₅₁₀₀₀_Reims,_France m_Service_de_gynécologie_{obstétrique,}_CHI_Poissy,₇₈₃₀₀_Poissy,_France n_Service_de_gynécologie_{obstétrique,}_Hopital_Bichat,₇₅₀₁₈_Paris,

France

o

Servicedechirurgieoncologique,CHU,Liege,Belgique,France

p_Service_de_{gynécologie,}_Hôpital_{Lariboisière,}₇₅₀₁₀_Paris,_France q_Service_de_{gynécologie,}_CHU_Tours,₃₇₀₀₀_Tours,_France

* Correspondingauthorat:Servicedegynécologie,Hôpitalsud,16 BDdeBulgarie,35000Rennes,France. E-mailaddress:Vincent.lavoue@gmail.com(V.Lavoue).