Intravesicle Bacillus Calmette–Guérin (BCG) Treatment for Non-Muscle Invasive Bladder Cancer (NMIBC) in the Transplanted Patients Population: A Systematic Review of the World Literature Omer A Raheem 1 , Ehab A Eltahawy 2 , Rodney Davis 2 and Mohamed H. Kamel *2 1 Department of Urology, University of California, USA 2 Departments of Urology, University of Arkansas for Medical Sciences, USA * Corresponding author: Mohamed H. Kamel, Associate Professor, Department of Urology, University of Arkansas for Medical Sciences, USA, Tel: 501-686-6916; Fax: 501-603-1422; E-mail: mkamel@uams.edu Rec date: Nov 21, 2014, Acc date: Dec 15, 2014, Pub date: Dec 17, 2014 Copyright: © 2014 Raheem OA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Intravesicle Bacille Calmette-Guerin (BCG) is generally considered to be contraindicated in the immunosuppressed or compromised patients with bladder cancer (BC) because of ineffectiveness or partial toxicities. Therefore, there is little experience with BCG in individual with impaired immune system and this can be challenging to practicing urologists. We sought to review the current available evidence of utilizing intravesicle BCG for BC in patients with solid organ transplantation and commented on its current status. Keywords: Bacillus calmette-guerin; Non muscle invasive bladder cancer; Transplanted patients Introduction Bladder cancer (BC) is the 8 th leading cause of cancer death in men in the United States (US). It is estimated that 74,690 patients will be diagnosed with BC in the US during the year 2014 [1]. In general, the non-metastatic BC is defined as a spectrum of bladder disease and traditionally classified into two broad categories: non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). NMIBC is a bladder cancer that is limited to the bladder mucosa or lamina propria of the bladder wall. The distinction between NMIBC and MIBC is critical. NMIBC constitutes majority of BC (80%) and can usually be treated with transurethral resection of bladder tumor (TURBT) and concomitant and/or subsequent administration of intravesicle treatments such as immunotherapy of Bacillus Calmette– Guérin (BCG) or chemotherapy of Mitomycin-C (MMC). Although 20% of BC cases presents with MIBC, these patients typically undergo more extensive local radical therapy with radical cystectomy and urine diversion or radiotherapy [2]. Recent contemporary data have shown that 5 years overall survival of NMIBC is 96% compared to 70% for the MIBC [1]. It is well established that solid organ transplantation is significantly associated with increased risk of BC. Buzzeo et al. examined the predicted risk of developing BC in the renal transplant recipients using the University of Wisconsin renal transplant database. Buzzeo’s result demonstrated that the relative risk of developing BC in the renal transplant patients is 3.31 higher than the general population risk [3]. Ehdaie et al. examined the Surveillance, Epidemiology, and End Results (SEER) database defining the BC characteristics in the renal transplant patients’ population, compared to all patients with BC included in the dataset [4]. This study highlights the patients with renal transplant and End-Stage Renal Disease (ESRD) presenting with BC tended to be younger, more likely to present with higher BC grade and stage [4]. Furthermore, BC was more likely to occur in the first 4 years post renal transplantation [4]. Methods A detailed, comprehensive literature review was performed to identify all published peer-reviewed articles which describe intravesicle BCG treatment for BC and transplanted patients in the urological literature. The search was conducted through MEDLINE® database, the Cochrane Library® Central Search, and the Web of Science. Initial search terms were BCG for BC and transplanted patients. Search results were screened for appropriate studies with particular emphasis placed on clinical and experimental studies as well as review articles. Articles referenced were screened to maximize review and inclusion of pertinent data. While English language text was not a specific search parameter, only English language publications were considered. All relevant studies collected were carefully examined to extract relevant data pertained to intravesicle BCG and transplanted patients. Evidence Synthesis for this Systematic Review Once it’s first introduced, BCG vaccine is a live attenuated vaccine that was initially used as an intravesicle treatment for NMIBC originally described by Morales in 1976 [5]. Intravesicle BCG is considered an immunotherapy for treatment of BC. The mechanism of action involves binding to fibronectin in the bladder wall. This binding stimulates the production of several cytokines with strong antitumor affect including granulocyte macrophage colony stimulating factor (GM-CSF), tumor necrosis factors (TNF) α, interferon (IF) ɣ and multiple Interleukins (IL) in both the bladder wall and urine. A mechanism involving activation of T-helper response is evidenced by an increase in IF- ɣ and IL-2 and IL-12 [6]. Intravesicle BCG is considered the most effective adjuvant treatment for NMIBC following transurethral resection of bladder tumors [7]. It is effective in reducing recurrence and progression of NMIBC by 40% and 25% Raheem et al., J Transplant Technol Res 2015, 5:1 DOI: 10.4172/2161-0991.1000144 Review Article Open Access J Transplant Technol Res ISSN:2161-0991 JTTR, an open access journal Volume 5 • Issue 1 • 1000144 J o u r n a l o f T r a n s p l a nt a t i o n T e c h n o l o g i e s & R e s e a r c h ISSN: 2161-0991 Journal of Transplantation Technologies & Research