30 Aug 2020

BCG-UL INSTILAT ÎN VEZICA URINARĂ LA PACIENȚII CU CANCER VEZICAL REDUCE RISCUL DE COVID 19? Autori:Dr Gluck G.Dr Radu B.Dr.Ionescu Angelica,Dr Boar A. ,Prof. Dr.Sinescu I.,

Modern Medicine | 2020, Vol. 27, No. 2 103 Intravesical BCG: Possible Protective Impact Against COVID-19 in NMIBC P atients Gabriel GLUCK1 , B. RADU1 , Angelica IONESCU1 , A. BOAR1 , Ioanel SINESCU1 1 Clinic of Urology and Renal Transplantation, Fundeni Hospital, Bucharest, Romania Corresponding author: Gabriel GLUCK, Clinic of Urology and Renal Transplantation, Fundeni Hospital, Bucharest, Romania. E-mail: gabrielgluck@yahoo.com Abstract Purpose: To determine the incidence of COVID 19 in a series of registered patients with non-muscle invasive bladder cancer, treated by TUR-BT and intravesical BCG. Patients and method: We analysed 127 patients with nonmuscle invasive bladder cancer, in the medium/high risk group, registered between 2001-2020. The patients and families have been contacted by phone. In this interval, 32 patients deceased (cardiovascular pathologies, non-urologic neoplasia, tumour progression), 95 patients are still alive, 24 women and 71 men. The average age was 61.7 (16-86), the majority being over 50, included in the high-risk group for COVID-19. The patients were resected endoscopically and received a cytostatic instillation within the fi rst 6 hours. Reresection of the tumour bed was practiced in pT1patients. The adjuvant treatment with BCG was used in the induction form at each relapse and maintenance (22 patients), respectively. Until 2005, we used the local strain (Cantacuzino Clinical Institute), after that, the strain from Bulgaria (Calgevax) and Medac (Germany). Results: 95 patients are still alive. Tumour relapses were registered in 34 patients. 3 patients registered tumour progression, resolved through radical cystectomy (2) and irradiation. In 3 cases, upper tract urothelial tumours were registered (nephroureterectomy with perimeatic cystectomy). 63 patients underwent induction treatment, while 22 underwent maintenance treatment. Complications: Intolerance to BCG in 4 patients, BCG cystitis in 5 patients, arthritis in 1 patient, septic status in 2 patients. In the analysed batch of patients, no COVID-19 cases have been registered. Conclusions: It appears that the intravesical administration of BCG represents an immunologic booster (confi rmable through PPD), resulting in a reduction of the COVID-19 infection incidence. Keywords: COVID-19, bladder cancer, BCG.

Rezumat Scop: Stabilirea incidenţei COVID -19 la pacienţii care sunt în evidenţa clinicii cu cancer non-invaziv de vezică urinară, trataţi prin TURV și BCG intravezical. Pacienţi și metodă: Am analizat 127 de pacienţi cu tumori non-invazive ale vezicii urinare, în grupa de risc mediu/ mare, luaţi în evidenţă între 2001-2020.Pacienţii sau familiile au fost contactate telefonic. În acest interval au decedat 32 de pacienţi (patologie cardiovasculară, neoplazii non-urologie, progresie tumorală), 95 de pacienţi sunt în viaţă: 24 de femei și 71 de bărbaţi. Vârsta medie a fost de 61,7 (16-86) ani, majoritatea cu vârsta peste 50 de ani în grupa de risc mare pentru COVID-19.Pacienţii au fost rezecaţi endoscopic și au primit o instilaţie cu citostatic în primele 6 h. La cei în pT1, s-a practicat rerezecţia patului tumoral. Tratamentul adjuvant cu BCG s-a folosit în forma de inducţie la fi ecare recidivă, respectiv întreţinere (22 de pacienţi).Până în 2005 am utilizat tulpina autohtonă (IC Cantacuzino), apoi cea din Bulgaria (Calgevax) espectiv Medac (Germania). Rezultate: 95 de pacienţi sunt în viaţă. Recurenţe tumorale s-au înregistrat la 34 de pacienţi. 3 pacienţi au avut progresie tumorală, soluţionată prin cistectomie radical (2) respectiv prin iradiere. În 3 cazuri au dezvoltat ORIGINAL PAPER Gabriel GLUCK et al. 104 Modern Medicine | 2020, Vol. 27, No. 2 Th e patients or families have been contacted by phone. In this interval, 32 patients deceased (cardiovascular pathologies, non-urologic neoplasia, tumour pro gression), 95 patients are still alive, 24 women and 71 men. Th e average age was 61.7 (16-86), the majority being over 50, included in the high-risk group for COVID-19. Th e patients were resected endoscopically and received a cytostatic instillation within the fi rst 6 hours. Reresection of the tumour bed was practiced in pT1 patients. Th e adjuvant treatment with BCG was used in the induction form at every relapse and maintenance (22 patients), respectively. Until 2005, we used the local strain (Cantacuzino Clinical Institute), after that, the strain from Bulgaria (Calgevaz) and Medac (Germany). RESULTS 95 patients are still alive; 16 patients were pTa, but high risk, 75 patients were pT1, 4 patients were pT2. Th e tumour relapses were registered in 34 patients. 3 patients registered tumour progression, requiring radical cystectomy (2) and irradiation, respectively. In 3 cases, upper tract urothelial tumours were registered (nephroureterecomy with perimeatic cystectomy). 63 patients underwent induction treatment, while 22 underwent maintenance treatment (12-36 months). Complications: intolerance to BCG in 4 patients, BCG cystitis in 5 patients, arthritis in 1 patient, sepsis in 2 patients. In the analysed batch of patients, no COVID-19 cases have been registered. DISCUSSIONS In adults, BCG vaccination is unable to off er complete protection against pulmonary tuberculosis, with an effi ciency range between 0 and 80%7-9, which exAbbreviations BCG - Bacillus Calmette–Guérin COVID-19 - Corona Virus Sars 2 NMIBC - Non muscle invasive bladder cancer PPD - Purifi ed Proteine Derivative TB - Tuberculosis Bacillus Calmette–Guérin (BCG) has been used for almost a century (since 1921) to prevent the tuberculosis infection. Countries with a national BCG vaccination program for the entire population appear to have a reduced incidence and death rate due to COVID-19. Th is might be explained by the known benefi ts of the immunity acquired through BCG vaccination. In countries were the BCG vaccination program has been paused (Italy, France, Th e Netherlands) the morbidity due to COVID-19 is clearly diff erent from other countries, where the vaccination is commonly practiced (countries from the Eastern Europe). COVID-19 incidence was 0,8/ millions inhabitants in countries with BCG vaccination programs and 34.8/ millions inhabitants in countries without vaccination programs. Also, the mortality amounted to 0.08 in countries with BCG vaccination and 34,8 in countries without vaccination program1,2,3,4. In the absence of a specifi c vaccination against COVID-19, the BCG vaccination based on population may play a role in reducing the impact of such disease5 . Th e BCG vaccination decreases the rates of infection with pneumonia, staphylococcus aureus and plays an important role in the protection against viruses, such as infl uenza, yellow fever and herpes6 . PATIENTS AND METHOD Patients and methods. We analysed 127 patients with non-muscle invasive bladder cancer, in the medium/high risk group, registered between 2001-2000. tumori de uroteliu înalt (nefroureterectomie cu cistectomie perimeatică).Tratament de inducţie au făcut 63 de pacienţi, tratament de întreţinere 22. Complicaţiile survenite: intoleranţă la BCG 4 pacienţi, cistită BCG 5 pacienţi,artrită 1 pacient, stare septică 2 pacienţi. În lotul de pacienţi analizat nu au fost cazuri de COVID-19. Concluzii: Se pare că și administrarea intra vezicală a BCG constituie un rapel imunologic (confi rmabil prin PPD), rezultând o reducere a incidenţei COVID-19. Cuvinte cheie: COVID-19, cancer de vezică, BCG.