Applicability of COVID-19 Pandemic Recommendations for Urology Practice: Data from Three Major Italian Hot Spots (BreBeMi)

Statistics

in

Urology

Applicability

of

COVID-19

Pandemic

Recommendations

for

Urology

Practice:

Data

from

Three

Major

Italian

Hot

Spots

(BreBeMi)

Paolo

Dell’Oglio

*

,

Giovanni

Enrico

Cacciamani

,

Fabio

Muttin

,

Giuseppe

Mirabella

,

Silvia

Secco

,

Marco

Roscigno

,

Federico

Alessandro

Rovati

,

Michele

Barbieri

,

Richard

Naspro

,

Angelo

Peroni

,

Antonino

Sacca`

,

Federico

Pellucchi

,

Aldo

Massimo

Bocciardi

,

Claudio

Simeone

,

Luigi

Da

Pozzo

,

Antonio

Galfano

,

on

behalf

of

COVID-19

Niguarda

Working

Group

a_{Departmentof Urology, ASST GrandeOspedale MetropolitanoNiguarda, Milan, Italy;}b_{Departmentof Urology, Antoni vanLeeuwenhoek Hospital,}

TheNetherlandsCancerInstitute,Amsterdam,TheNetherlands;c_{InterventionalMolecularImaginglaboratory,DepartmentofRadiology,LeidenUniversity}

MedicalCentre,Leiden,TheNetherlands;d_{UniversityofSouthernCaliforniaInstituteofUrology&CatherineandJosephArestyDepartmentofUrology,Keck}

SchoolofMedicine,UniversityofSouthernCalifornia,LosAngeles,CA,USA;e_{DepartmentofUrology,ASSTPapaGiovanniXXIII,Bergamo,Italy;}f_Department

ofUrology,ASSTSpedaliCivili,Brescia,Italy;g_{SchoolofMedicineandSurgery,Milano-BicoccaUniversity,Milan,Italy}

a v ai l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n al h o m e p a g e : w w w . e u - o p e n s c i e n c e . e u r o p e a n u r o l o g y . c o m Articleinfo Articlehistory: AcceptedJanuary21,2021 AssociateEditor: GuillaumePloussard Keywords: Coronavirus COVID-19 Urology

EuropeanAssociationofUrology guidelines

SAR-CoV-2 Triage

Abstract

Background: LombardyhasbeenthefirstandoneofthemostaffectedEuropean regionsduringthefirstandsecondwavesofthenovelcoronavirus(severeacute respiratorysyndromecoronavirus2[SARS-CoV-2]).

Objective: Toevaluatetheimpactofcoronavirusdisease2019(COVID-19)onall urologic activitiesover a 17-wk period in thethree largest public hospitals in LombardylocatedintheworsthitareainItaly,andtoassesstheapplicabilityofthe authorities’recommendationsprovidedforreorganisingurologypractice. Design,setting,andparticipants: Aretrospectiveanalysisofallurologicactivities performedat threemajor publichospitalsin Lombardy (Brescia, Bergamo,and Milan),fromJanuary1toApril28,2020,wasperformed.

Outcomemeasurementsandstatisticalanalysis: Join-pointregressionwasusedto identify significant changesin trendsfor allurologicactivities. Average weekly percentage changes (AWPCs) were estimatedto summarise linear trends. Uro-oncologicsurgeriesperformedduringthepandemicweretabulatedandstratified accordingtothefirstpreliminaryrecommendationsbyStenslandetal(Stensland KD, Morgan TM, Moinzadeh A, et al. Considerations in the triage of urologic surgeriesduringtheCOVID-19pandemic.EurUrol2020;77:663–6)andaccording tothelevelofpriorityrecommendedbyEuropeanAssociationofUrology guide-lines.

y _{Theseseniorauthorscontributedequallytothepaper.}

*Correspondingauthor.DepartmentofUrology,ASSTGrandeOspedaleMetropolitanoNiguarda, Milan,Italy.Tel.:+3407981232;Fax:+3407981232.

E-mailaddress:paolo.delloglio@gmail.com(P.DellOglio).

http://dx.doi.org/10.1016/j.euros.2021.01.012

2666-1683/©2021TheAuthor(s).PublishedbyElsevierB.V.onbehalfofEuropeanAssociationofUrology.Thisisanopenaccessarticle undertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction

At the end of the 21st century, we have been facing a secondwaveofaninternationalpublichealthemergency,a respiratorydisease(coronavirusdisease2019[COVID-19]) caused by a novel coronavirus (severeacute respiratory syndromecoronavirus2[SARS-CoV-2])[1,2].Asof Novem-ber14,2020,atotalof53164803confirmedcasesand1 300576confirmeddeathsin220countrieswererecorded, accordingto theWorld HealthOrganization(WHO) data

[3]. Since its outbreak in December 2019 in China [4], COVID-19hasspreadrapidlyallaroundtheworld,seeing ItalyasthefirstEuropeancountrytobehitbythevirusand oneofthemostaffectedcountries[5,6].Thefirstcase of COVID-19inItalywasreportedonFebruary21,2020,inthe Lombardyregion,whichsincethenhasalwaysbeenontop of the ranking also during the secondwave, with 1144 552confirmedcasesand44683deathsasofNovember14,

2020[7,8].Milan,Brescia,andBergamohavereportedthe

highest number of cases since the beginning of this outbreak[7,8].Someauthorsreportedtheirexperienceand thedramaticchangescausedbyCOVID-19inthe manage-mentofurologicactivities[9–14].However,themajorityof thesereportsarequalitativestudiesthatdidnotquantify theimpactofthisemergencyonurologicactivities[9,14]or exclusively focused on the reduction of one urologic activity (ie, surgery orurologic emergencies) duringthe early phase of COVID-19 emergency [10–13], combining data of several European centres with different local capacitiesanddifferentlocalincidences[11].Therefore,a clear overview of the repercussions of SARS-CoV-2 on urologicpracticeislacking.Moreover,itbecame

challeng-ing to identify which uro-oncologic patients required nondeferrablemanagementinordertoavoiddelaying life-saving treatments [9]. During the first wave, several authorities [15–17], including urologic guidelines [18], redefined treatment options and timing of urologic surgical activities with the purpose of reorganising urologicpracticeduringtheCOVID-19pandemic.Thefirst recommendationswerepublishedbyStenslandetal[15]

onMarch15,2020,withtheinputofmultipledepartments inEuropeandtheUSA.Afteralmost2mo(April17,2020) sincetheCOVID-19outbreak,theEuropeanAssociationof Urology (EAU)guideline recommendationswereadapted to support urologists during this unprecedented health care crisis [18]. These recommendations were based exclusively on expert opinions, bringing into question whether they are applicable in public hospitals that became almostentirelydedicatedtoCOVID-19treatment andrequirevalidationaswearefacingthesecondflowof thispandemic.Tofillthesegaps,wequantifiedtheimpact of COVID-19 on urologic surgical volumes (oncologic, nononcologic, and emergency surgeries), consultations, admissions for urologic diseases, urologic consultations requested by the central emergency department (ED), prostate biopsies, and cystoscopies in the three largest publichospitalsinLombardylocatedinthehardesthitarea inItaly,namely,intheprovincesofBrescia,Bergamo,and Milan (BreBeMi),overa17-wkperiod(fromJanuary1to April28,2020).Moreover,theurologicsurgeriesprivileged since the COVID-19 outbreak in Italy were assessed to evaluate whether high-priority surgeries and timing of treatment recommended by the authorities [15,18] are applicable.

Resultsandlimitations: Thetrendfor2020urologicactivitiesdecreasedconstantly fromweeks8–9uptoweeks11–13(AWPCrange–41%,–29.9%;p<0.001). One-thirdofuro-oncologicsurgeriesperformedweretreatmentsthatcouldhavebeen postponed,accordingtothepreliminaryurologicrecommendations.High appli-cabilitytorecommendationswasobservedfornon–muscle-invasivebladder can-cer(NMIBC)patients with intermediate/emergencylevel ofpriority,penileand testicularcancerpatients,anduppertracturothelial cellcarcinoma(UTUC)and renal cell carcinoma (RCC) patients with intermediate level of priority. Low applicability was observed for NMIBC patients with low/highlevel of priority, UTUCpatientswithhighlevelofpriority,prostatecancerpatientswith intermedi-ate/highlevelofpriority,andRCCpatientswithlowlevelofpriority.

Conclusions: During COVID-19, we found a reduction in all urologic activities. High-prioritysurgeriesandtimingoftreatmentrecommendedbytheauthorities requireadaptationaccordingtohospitalresourcesandlocalincidence.

Patientsummary: Weassessedtheurologicsurgeriesthatwereprivilegedduring thefirstwaveofcoronavirusdisease2019(COVID-19)inthethreelargestpublic hospitals in Lombardy, worst hit by the pandemic, to evaluate whether high-prioritysurgeriesandtimingoftreatmentrecommended bythe authoritiesare applicable. Pandemicrecommendations provided byexperts should betailored accordingtohospitalcapacityanddifferentlevelsofthepandemic.

©2021TheAuthor(s).PublishedbyElsevierB.V.onbehalfofEuropeanAssociationof Urology.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense( http://creati-vecommons.org/licenses/by-nc-nd/4.0/).

2. Patientsandmethods 2.1. Datasource

Thecurrentstudyreliedonaretrospectivelymaintaineddatabasethat collected data on all urologic activities performed at Spedali Civili (Brescia), Papa Giovanni XXIII (Bergamo), and Grande Ospedale MetropolitanoNiguarda(Milan)fromJanuary1toApril28,2020.The Departmentof Urologyof SpedaliCivili (Brescia) has64 beds,it is normallystaffedby14full-timeurologists,and4000urologicsurgeries areperformedannually.TheDepartmentofUrologyofPapaGiovanni XXIII(Bergamo) has40 beds,it is normally staffed by 13full-time urologists,and2500 urologicsurgeries areperformedannually.The DepartmentofUrology ofGrandeOspedale Metropolitano Niguarda (Milan)has20beds,itisnormallystaffedby11full-timeurologists,and 1900urologicsurgeriesareperformedannually.

2.2. Statisticalanalysis

Statisticalanalysisconsistedoffivesteps.First,aretrospectivechart reviewofallurologicactivities(ie,allurologicsurgeries,emergencyand oncologic surgeries, cystoscopies, prostate biopsies, consultations, admissionsforurologicdiseases,andurologicconsultationsrequested bythecentralED)ofthethreeurologicdepartmentsfromJanuary1to April28,2020wasperformed.Theurologicactivitywasassessedweekly andcomparedwith2019urologicactivityduringthesametimeframeto provideacontrolgroup.Datareferringtothesameweeksof2019and 2020werematched.Second,ajoin-pointregressionmodelwasusedto identify statistically signi_ficant changesin trends for each urologic activityovertime[19,20].Averageweeklypercentagechange(AWPC) and95%confidenceintervals(95%CIs)wereestimatedtosummarise lineartrendsduringthetimeframeassessed.Third,weeklyurologic

activities weretemporallycorrelatedwith theweeklyincidenceand mortalityofCOVID-19inLombardyrelyingonthePearsoncorrelation method.COVID-19epidemiologydataonincidenceandmortalitywere obtainedfromtheItalianMinistryofHealth[8].Fourth,weassessedthe “lagtime_”betweenthe_firstCOVID-19caseinLombardy(February21), the WHO public declaration of emergency (January 30), the Italian declarationoflockdown(March9),andthereduction/blockageofthe urologicactivitiesbythegovernmentofLombardy.Fifth,weassessed whichurologicsurgerieswereprivilegedfromFebruary21toApril28, 2020, to evaluate whether high-priority surgeries and timing of treatmentrecommendedbytheauthorities[15,18]areapplicableduring thishealthcarecrisis.Uro-oncologicsurgeriesperformedinthethree urologicdepartmentsweretabulatedandstratifiedaccordingtothefirst preliminaryrecommendationsbyStenslandetal[15]onMarch15,2020, andaccordingtothelevelofpriorityrecommendedbytheCOVID-19EAU guidelinesonApril17,2020[18].AnalyseswereperformedusingtheR softwareversion3.5.1(RFoundationforStatisticalComputing,Vienna, Austria)andJoinPointTrendAnalysisSoftwareversion4.2.0.2(Statistical ResearchandApplicationsBranch,NationalCancerInstitute,St.Louis, MO,USA).

3. Results

3.1. Trendpatternanalysis

During2019,theweeklyamountofurologicsurgeries(AWPC –0.3; 95%CI –1.5,1; p=0.6; Fig.1A), emergency urologic surgeries(AWPC–0.3;95%CI–2.2,1.6;p=0.7;Fig.1B), uro-oncologic surgeries (AWPC+0.4; 95% CI –1.1,1.9; p=0.6;

Fig.1C),cystoscopies(AWPC+0.2;95%CI–1.4,1.8;p=0.8;

Fig. 1D), prostate biopsies (AWPC –0.8; 95%CI –3.4,1.8; p=0.5;Fig.1E),urologicconsultations(AWPC–0.8;95%CI

Fig.1–WeeklyurologicactivityperformedbetweenJanuary1andApril28in2019and2020,inthethreelargestpublichospitalsinLombardylocated intheworsthitareainItaly(Brescia,Bergamo,andMilan):(A)allurologicsurgeries,(B)emergencyurologicsurgeries,(C)uro-oncologicsurgeries,(D) cystoscopies,(E)prostatebiopsies,(F)urologicconsultations,(G)admissionsforurologicdiseases,and(H)urologicconsultationsrequestedbythe centralemergencydepartment.

–2.2,0.7;p=0.3;Fig.1F),admissions forurologicdiseases (AWPC–0.9;95%CI–2.3,0.5;p=0.2;Fig.1G),andurologic consultationsrequestedbythecentralED(AWPC+0.5;95% CI–0.2,1.2;p=0.1;Fig.1H)performedwasfairlystableover time. Conversely, the trend for 2020 urologic surgeries decreased constantlyfromweek 8 upto week12 (AWPC –29.9;95%CI–40,–18.3;p<0.001),followedbyasignificant increase(AWPC+14.1;95%CI6.5,22.2;p<0.001;Fig.1A).A not statistically significant decrease was observed for 2020emergencyurologicsurgeriesfromweek8uptoweek 12(AWPC–25.5;95%CI–46.9,4.5;p=0.1;Fig.1B).Thereafter, anonstatisticallysignificantincrementof2020emergency urologicsurgerieswasobserved(AWPC+10.2;95%CI–5.3, 28.2;p=0.2;Fig. 1B).Onthecontrary,thetrendfor2020 uro-oncologicsurgeriesshowedasharpsignificantdecreasewith anAWPCof–41(95%CI–60,–13;p<0.001)fromweek8up toweek12,followedbyastatisticallysignificantrise(AWPC +34.9;95% CI 13.3, 60.5; p<0.001;Fig.1C).A significant constantly decreasing trend was observed also for 2020 cystoscopies (AWPC –37; 95% CI –46.7, –25.5; p<0.001) from week 9 up to week 13, followed by a statisticallysignificant increase(AWPC+28.6; 95%CI15.6, 42.9;p<0.001;Fig.1D).Ajoin-pointregressionanalysisof 2020 weekly prostate biopsies showed a nonstatistically significantreductionfromweek9uptoweek12,withan AWPCof–77(95%CI–97.3,94.8;p=0.2;Fig.1E),andthenan increaseup to week 17 (AWPC+84.4; 95%CI 14.4,197.2; p<0.001; Fig.1E). Similarly, the trend for 2020 urologic consultations showed a significant constantly decreasing trendfromweek8uptoweek12(AWPC–37.8;95%CI–53.7, –16.4;p<0.001),followedbyanotstatisticallysignificant

increment(AWPC+8.3;95%CI–5.2,23.6;p=0.2;Fig.1F).A significantdropwasfoundfor2020admissionsforurologic diseasesfromweek7uptoweek12(AWPC–36.5;95%CI –46.4,–24.8;p<0.001;Fig.1G),thenrose upto week17 (AWPC+13.8;95%CI1,28.4; p<0.001;Fig.1G).The join-pointregressionanalysisof2020weeklyurologic consulta-tions requested by the central ED showed a constant significant decrease from week 8 up to week 11 (AWPC –36.5;95%CI–49.1,–20.9;p<0.001;Fig.1H).Achangein trendovertimewasobservedthereafter(AWPC+12.3;95%CI 8.2,16.6;p<0.001;Fig.1H).

Supplementary Table1shows thecorrelationbetween weekly urologic activities and weekly incidence and mortalityof COVID-19inLombardy.Theweeklydecrease trends of all urologic activities in 2020 from week 8/9 correlatedstronglywith theupswinginweeklytrendsof incidenceandmortalityofCOVID-19inLombardy (correla-tion coefficient ranged between –0.98 and –0.83; all p0.03;SupplementaryTable1).

Alagtimeanalysisrevealedasharpdecreaseofurologic surgeries (Fig. 1A–C), urologic consultations (Fig. 1F), admissions for urologic diseases (Fig. 1G), and urologic consultationsrequestedbythecentralED(Fig.1H)sincethe firstCOVID-19caseinItalyfromweek8.Conversely,adelay of 1 wk was observed for a reduction of diagnostic procedures(ie,cystoscopiesandprostatebiopsies;Fig.1D and 1E). Moreover, a lag time analysis revealed thatthe initialreductionofurologicactivitieswasobserved>3wk afterWHOpublicdeclarationofemergency(Fig.1)andthat the Italianlockdownwas declaredon March 9,when all urologicactivitieswerereducedby>50%(Fig.1).

3.2. Applicabilityofauthorities’recommendations

FromFebruary 21 to April 28, 2020,15 patients refused urologicsurgeryinthethree hospitals.Allthesepatients were candidates to transurethral resection for bladder tumour(TURBT).Overall,232uro-oncologicsurgerieswere performed during the time frame assessed (Table 1). Of these, 161 (69.4%) and 71 (30.6%) were, respectively, surgeries that should be prioritised and delayed during COVID-19accordingtotherecommendationsofStensland etal [15]. Atotal of 104 (44.8%) and24 (10.3%) patients underwentTURBTfor suspectedcT1+tumourandradical cystectomy with extendedpelvic lymph node dissection (ePLND),respectively.Ofthepatients,10%(n=23) under-wentpartial(PN)orradical(RN)nephrectomyforcT1aor T1btumour. Overall, 4.7%(n=11), 4.7%(n=11),and 5.2% (n=12)underwent orchiectomy, TURBT fornonsuspected cT1+tumour,andradicalprostatectomy(RP) withePLND forlocallyadvancedprostatecancer(PCa;Table1).Lessthan 4% of the uro-oncologic surgeries performed during the COVID-19emergencywererepresentedbyRNforpatients withcT3renaltumour(n=5;2.2%),PNorRNforpatients harbouring cT2a/T2b renal tumour (n=8; 3.4%),RP with ePLND for intermediate-risk (n=8; 3.4%) and high-risk (n=9; 3.9%) PCa patients, kidney-sparing surgery/radical nephroureterectomyforpatientswithlow-(n=4;1.7%)and high-risk(n=9;3.9%)uppertracturothelialcellcarcinoma (UTUC), adrenalectomy for patients harbouring adrenal tumour>6cm(n=3,1.3%),andtotalpenectomyforpatients withpenilecancer(n=1;0.4%).

Table 2 shows the type of uro-oncologic surgeries

performed during the time frame assessed, stratified

according to the levelof priority (low, intermediate,and highpriority,andemergency)recommendedbyCOVID-19 EAU guidelines [18]. For non–muscle-invasive bladder cancer (NMIBC), 0%, 90%, 42%, and 100% applicability of COVID-19 EAU guidelinerecommendations was observed for, respectively, low-, intermediate-, high–priority, and emergency surgeries. Regarding UTUC, 100% and 11% applicabilitywasacknowledgedfor,respectively, interme-diate- and high-priority surgeries. For muscle-invasive bladdercancer(MIBC),applicabilityof88%to intermediate-and70%tohigh-prioritysurgeriesaccording toCOVID-19 EAUguidelinerecommendationswereshown.Forrenalcell carcinoma (RCC)patients, weshowed applicability of8%, 100%, and 82% for,respectively, low-, intermediate-, and high-prioritysurgeries.RegardingPCapatients, applicabili-tyof0%and33%wasobservedfor,respectively, intermedi-ate-andhigh-risk-prioritysurgeries.Finally,forpenileand testicularcancerpatients,applicabilityof100%toCOVID-19 EAU guideline recommendations was acknowledged

(Table2).

4. Discussion

Our analyses demonstrated several noteworthy findings. First, an overwhelming decrease was observed for all 2020 urologic activities assessed since the COVID-19 outbreak in Italy from week 8/9 up to weeks 11–13. Thereafter,allurologicactivitiesshowedaconstantincrease up to the end of the time frame assessed. These trends mirroredtheCOVID-19epidemiologytrendsinLombardyin terms of incidence and mortality. Especially, a negative correlationwasobservedbetweenallurologicactivitiesand Table1–Uro-oncologicsurgeries(232intotal)performedinthethreelargestpublichospitalsinLombardylocatedinthemostaffectedarea inItaly(Brescia,Bergamo,andMilan)fromFebruary21toApril28,2020,accordingtoStenslandetal_’s[15]recommendations

Stensland recommendations

Disease Typeofsurgery Patients

treated,n(%)

Patients treated,n(%)

Surgeriesthatshould beprioritised

Bladdercancer RC 24(10.3) 161(69.4)

TURBTforsuspectedcT1+tumour 104(44.8)

Testicularcancer Orchiectomy 11(4.7)

KidneycancerforcT3+tumours, includingpatientswithrenal veinand/orIVCthrombi

RN 5(2.2)

High-riskUTUC RNU/kidney-sparingsurgery 9(3.9;8RNUand

1kidney-sparingsurgery)

Low-riskUTUC Kidney-sparingsurgery 4(1.7)

Adrenaltumour(>6cm) Adrenalectomy 3(1.3)

Penilecancer Totalpenectomy 1(0.4)

Surgeriesthatshould bedelayeda

Bladdercancer TURBTnotsuspectedforcT1+tumour 11(4.7) 71(30.6)

KidneycancerforcT2a/T2btumours PNorRN 8(3.4)

KidneycancerforcT1a/T1btumours PNorRN 23(9.9)

Intermediate-riskPCa RP+ePLND 8(3.4)

High-riskPCa RP+ePLND 9(3.9)

High-risk(locallyadvanced)PCa RP+ePLND 12(5.2)

ePLND=extendedpelviclymphnodedissection;IVC=inferiorvenacava;PCa=prostatecancer;PN=partialnephrectomy;RC=radicalcystectomy;RN=radical nephrectomy;RNU=radicalnephroureterectomy;RP=radicalprostatectomy;TURBT=transurethralresectionofbladdertumour;UTUC=uppertracturothelial cellcarcinoma.

a

cT1renalmassesshouldbedelayedorotherformsofablativeapproachesshouldbeconsidered;cT2renalmassesshouldbeconsideredfordelaybasedupon patient-specificconsiderations,suchasage,morbidity,symptoms,andtumourgrowthrate.Mostprostatectomiesshouldbedelayed.Ifhigh-riskPCapatientsare ineligibleforradiationtherapy,radicalprostatectomyshouldbeconsidered.

weekly trends of incidence and mortality of COVID-19 duringtheupswinginthepandemicphase.Overall,these findings display strongly the alteration of daily urologic clinicalpracticeduringCOVID-19outbreak.Indeed,allthree high-volumeurologicdepartmentsbecamealmostentirely dedicatedtothetreatmentofCOVID-19 patients. Specifi-cally, anaesthesiologists, nurses, and urologists were employed daily for managing acute COVID-19 patients. Moreover, the number of medical and paramedical staff infectedwithSARS-CoV-2wasrising.AsofApril21,2020,a totalof22000healthcareworkershavebeeninfectedin

Italy, representing 10% of overall positive cases in Italy

[21].Therefore,therewasalackofhealthcarepersonnel managingtheelectiveurologicsurgeries.Inaddition,beds generallyavailableforurologicprocedureswereneededfor the newly hospitalised COVID-19 patients, of whom approximately20%requiredintensivecareunitadmission

[22],furthercontributingtothedeclineinelectivesurgeries and patient admissions for urologic diseases observed during the upswing in the pandemic phase. Urologic consultations anddiagnostic procedures(ie, cystoscopies and prostate biopsies) were reduced as well during the Table2–Uro-oncologicsurgeriesperformedinthethreelargestpublichospitalsinLombardylocatedinthemostaffectedareainItaly (Brescia,Bergamo,andMilan)fromFebruary21toApril28,2020,stratifiedaccordingtothelevelofpriorityandtimingofsurgerydefinedby EAUguidelinesduringtheCOVID-19pandemic[18]

Disease Typeofsurgery

performed

Levelsofpriorityaccordingto EAUguidelinesduringCOVID-19

pandemic,%(n/N)

Timingofsurgeryaccording toEAUguidelinesduring

COVID-19pandemic

Applicability ofguideline recommendations,

%(n/N)a

105NMIBC 105TURBT 10(11/105)lowpriority Treatmentdeferredby6mo 0(0/11)

40(42/105)intermediatepriority Treatwithin3mo 90(38/42)

48(50/105)highpriority Treatwithin6wk 42(21/50)

2(2/105)emergency Treatwithin24h 100(2/2)

13UTUC 8RNU:

31(4/13)intermediatepriority Treatwithin3mo 100(4/4)

4Robot-assistedRNU 2OpenRNU

69(9/13)highpriority Treatwithin6wk 11(1/9)

2LaparoscopicRNU 5Kidney-sparingsurgeryb

(2distal ureterectomyand3RIRS)

34MIBC 24RC: 71(24/34)intermediatepriority Treatwithin3mo 88(21/24)

5Robot-assistedRC 19OpenRC

29(10/34)highpriority Treatwithin6wk 70(7/10)

10TURBT(forsuspiciousof invasivetumouratimaging)

36RCC 20PN: 36(13/36)lowpriority Treatmentdeferredby6mo 8(1/13)

14Robot-assistedPN 33(12/36)intermediatepriority Treatwithin3mo 100(12/12)

4OpenPN 31(11/36)highpriority Treatwithin6wk 82(9/11)

2LaparoscopicPN 16RN: 6Robot-assistedRN 2OpenRN 8LaparoscopicRN 2Adrenocortical carcinoma+ 1metastaticRCC

3Adrenalectomy Nopriorityprovidedbyguidelines Notimingprovidedby

guidelines –

1Robotassisted 1Open 1Laparoscopic

29PCa 29RP 59(17/29)intermediatepriority RPtopostponeuntilafter

pandemic;ifpatientsanxious considerADT+RT

0(0/17) 23Robot-assistedRP

6OpenRP

41(12/29)highpriority Treatwithin6wk 33(4/12)

11Penilecancer 1Totalpenectomy 100(1/1)highpriority Treatwithin6wk 100(1/1)

11Testicularcancer 11Orchiectomy 100(11/11)emergency Diagnoseandtreatwithin24h 100(11/11)

ADT=androgendeprivationtherapy;COVID-19=coronavirusdisease2019;EAU=EuropeanAssociationofUrology;MIBC=muscle-invasivebladdercancer; NMIBC=non–muscle-invasive bladder cancer; PCa=prostate cancer; PN=partial nephrectomy; RC=radical cystectomy; RCC=renal cell carcinoma; RIRS=retrograde intrarenal surgery; RN=radical nephrectomy; RNU=radical nephroureterectomy; RP=radical prostatectomy; RT=radiotherapy; TURBT=transurethralresectionofbladdertumour;UTUC=uppertracturothelialcellcarcinoma.

a

PatientstreatedwithinthetimingrecommendedbyEAUguidelines.

b

upswing in the pandemic phase to lower the risk of infectingelectivepatients.Prioritywasgiventoemergency consultations and patients with high-risk malignancies withinthe1styearoffollow-up.Asignificantreductionin urologicconsultationsrequestedbythecentralEDwasalso observed from weeks 8 to 11. This could partially be explainedbythealreadyreportedabuseofEDserviceby Italianpatientstoreducethelengthoftimefordiagnosis/ treatment of urologic diseases [12]. A further possible explanationcouldbethereluctancetoturntoEDservicefor thefearofbeinginfected,despitetheurgencyforurologic consultation [23]. A decrease during the upswing in the pandemicphasewasalsoobservedforemergencysurgeries. However,asexpected,thiswasnonstatisticallysignificant, suggestingthatemergencysurgeriescannotbepostponed becauseoftheirgravityevenduringpandemictime.Overall, this general decrease of the urologicactivities translates intomissed/delayeddiagnosesofurologicdiseases,deferral treatmentofmanyurologicmalignancies,andlessintensive oncologic follow-up of genitourinary cancer patients

[24].The consequencesofthisunprecedentedhealthcare scenarioareprematuretoestimate,andfuturedatawillbe produced in coming years that analyse the impact of diagnosis and treatment delays, and deintensification of follow-upon urologicoutcomes.Itmightendinahigher numberofpatientsbeingdiagnosedwithadvancedurologic diseases and an increased cancer-specific mortality rate, especially for more aggressive cancers[24]. At the same time,itmightbepossiblethatasignificanttreatmentdelay ofselectedearly-stagecancersorlessintensivefollow-up protocolswill not impact long-term outcomes adversely, providingevidencetoupdatecurrenturologicguidelines.To partiallylimittheconsequencesofthismassivebreakdown, sincethemiddle/endofMarch(weeks12–13;Fig.1)when the incidence and mortality for COVID-19 in Lombardy reached the peak, a changing tendency was observed: a slow, constant reopening of all urologic activities was observed in all three centres involved in the “red area”. Unfortunately,nowadayswearefacingthesecondwaveof this pandemic, reshaping again the health systems in severalcountriesworldwide.Itseemsremotethatmedical practicewill returntopre-COVID-19patternsinthenear future. Therefore, it becomes imperative to adapt and modify our urologic practice. In this regard, in order to reduce in-personinteractionsand theconsequentrisk of contagion,anincreasinginteresthasbeenobservedforthe application of telemedicine to provide urologic care

[25,26]. Evidence suggested that telemedicine has been

implantedsuccessfullyinseveralurologicconditions[26], makingitappealingalsoaftertheendofthisemergency.

Second,weobservedapromptreplyinthereductionof urologicactivitiesbyLombardyregionrelativetothefirst COVID-19caseinItaly,exceptfordiagnosticprocedures(ie, cystoscopiesandprostatebiopsies),whichstartedtoshowa drop-off1wklater.Notably,theWHOpublicdeclarationof emergencydidnotinfluencethereductionofallurologic activities,andtheItaliandeclarationoflockdownarrived when the urologic practice had already been reduced overwhelmingly (Fig.1).Overall,thesefindings suggesta

time gap between the onset of the emergency and the central government decisions. Nevertheless, it has to be acknowledged that the Italian government has been the firstamongthewesterncountriestofacethedecisionofa nationallockdown.

Third, when we assessed the uro-oncologic surgeries performed fromFebruary21, 2020to April 28, 2020,we observedthat70%werehigh-prioritysurgeriesaccordingto therecommendationsbyStenslandetal[15].Notably,30% of thesesurgeries were treatments thatcouldhavebeen postponed according to the expert recommendations

(Table1)[15].Whenweretrospectivelyassessedwhether

thetreatmentoptionsand,especially,thetimingofurologic surgical activitiesredefinedbyEAUguidelinesduringthe COVID-19pandemic[18]areapplicable,weobservedhigh applicability (ie, 90–100%) for NMIBC patients with intermediateandemergencylevelsofpriority,penileand testicularcancerpatients,andUTUCandRCCpatientswith intermediate level of priority (Table 2). Intermediate applicability (ie, 70–89%) was observed for MIBC with intermediateandhighlevelsofpriorityandforRCCwith high levelofpriority.Conversely,lowapplicability (ie,0– 69%)wasidentifiedforNMIBCpatientswithlowandhigh levelsofpriority,UTUCpatientswithhighlevelofpriority, PCapatientswithintermediateandhighlevelsofpriority, andRCCpatientswithlowlevelofpriority.Theconsiderable rateofnonprioritysurgeriesthatwereperformed(Table1) and the lowapplicability of guidelinerecommendations, especially for malignancies defined as high priority

(Table2),wereexpected,consideringthesingledepartment

case mix and bearing in mind that typically urologic departmentsfighttotreaturo-oncologicpatientswithinthe deadline(ie,30d)proposedbyregionalguidelinesoutside the COVID-19 era [9]. The findings observed might be explainedbythefactthaturologistshadtostrugglewitha new scenario: reorganise the operating rooms (ORs) according to urologically prioritised malignancies [24], reduced number of accessible ORs, available health care staff,andnumberofelectivevacanturologicandintensive careunitbeds[22],andmovetoCOVID-freestructuresto treaturologicpatientsandpatientswhorefusedtoreceive anykindoftreatmentduringtheCOVID-19period.Overall, theseresultssuggestthaturologicpandemic recommenda-tions provided by experts [15,18] should be tailored according to hospital capacity anddifferent levelsof the pandemic.Thisisthekeyandcouldprovideamodelfor on-going care in case of future pandemics with novel pathogens.

Ourstudyisnotdevoidoflimitations.First,ourfindings derivefromthethreeItalianpublicurologicdepartments mostaffectedbythispandemic.Second,whenweassessed theapplicabilityofCOVID-19pandemicrecommendations, wedidnotaccountforthosepatientswhorefusedsurgery (n=15).However,itisofnotethatnoneofthesepatients wasacandidateformajororminorsurgeries (ie,TURBT) with high/emergency priority level. Conversely, all these patientswerecandidatesforTURBTwithlow/intermediate prioritylevel.Therefore,itisunlikelythattheapplicability ofCOVID-19 guidelinerecommendationsprovidedbyour

studywouldhavebeenaffectedsignificantly.Third,allthese threedepartmentsarehigh-volumecentreswhere gener-allymoreadvancedmalignanciesaretreated.Therefore,the epidemic could have had a different impact in other divisions outside the hotspot of Brescia, Bergamo, and Milan,withlowercaseload.However,thisreportrepresents thefirststudythatquantifiedtheinfluenceofCOVID-19on all2020urologicactivitiesovera17-wkperiod,andthefirst studytocorrelatethetrend ofallurologicactivitieswith COVID-19 epidemiology data throughout the COVID-19 pandemic period and with the public declarations of emergency/lockdown. Last,thisrepresents thefirststudy thatevaluateswhetherhigh-prioritysurgeriesandtiming of treatment, recommended by several authorities, are applicable in the urologicdepartments worst hit by this pandemic.

5. Conclusions

Allurologicactivitiesinthethreelargestpublichospitalsin Lombardy, worst hit by the pandemic, underwent a considerablereductionthroughouttheCOVID-19pandemic period. High-priority surgeries and timing of treatment recommended by the authorities require adaptation accordingtohospitalresourcesandlocalincidence.Overall, our results call for Italian government endorsement of recommendationsbytheauthorities,inordertoguarantee propertreatmentduringapandemic.Thisiscrucialaswe arefacingasecondwaveofthedisease.

Authorcontributions:PaoloDell_’Ogliohadfullaccesstoallthedatain thestudyandtakesresponsibilityfortheintegrityofthedataandthe accuracyofthedataanalysis.

Studyconceptanddesign:Dell_’Oglio,Cacciamani,Galfano. Acquisitionofdata:Dell_’Oglio,Muttin,Secco,Rovati,Barbieri. Analysisandinterpretationofdata:Dell’Oglio,Cacciamani,Galfano. Draftingofthemanuscript:Dell’Oglio.

Critical revision of the manuscript for important intellectual content: Cacciamani,Muttin,Mirabella,Secco,Roscigno,Rovati,Barbieri,Naspro, Peroni,Saccà,Pellucchi,Bocciardi,Simeone,DaPozzo,Galfano. Statisticalanalysis:Dell_’Oglio,Cacciamani.

Obtainingfunding:None.

Administrative,technical,ormaterialsupport:Galfano. Supervision:Simeone,DaPozzo,Galfano.

Other:None.

Financial disclosures: Paolo Dell’Oglio certifies that all conflicts of interest, including specific financial interests and relationships and affiliationsrelevanttothesubjectmatterormaterialsdiscussedinthe manuscript(eg,employment/affiliation,grantsorfunding, consultan-cies,honoraria,stockownershiporoptions,experttestimony,royalties, orpatents_filed,received,orpending),arethefollowing:None. Funding/Supportandroleofthesponsor:None.

AppendixA. Supplementarydata

Supplementary material related to this article can be found,intheonlineversion,atdoi:https://doi.org/10.1016/j.

euros.2021.01.012.

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