We reviewed a series of ten bladder caner cases with HIV-infected in Beijing Youan Hospital, which is the largest HIV follow-up center in China.This literature is the largest published series of this crew in Asia at present.
Advanced age, male sex, and cigarette smoking were considered to be main risk factors contribute to the development of bladder cancer [11].The median onset age of bladder caner cases with HIV-infected in our study was 51 years old, and it was slightly younger than the published largest series of this crew at an meidan age of 55 and 56 years respectively [8,9],while the median age of diagnosis of baladder cancer had been demonstrated between 70 and 84 years in genneral population[11]. It was astonished that ten cases were all males casually, which strongly supported a male preponderance documented in published series of this crew[8,9] and was in accordance with the general population proved by physicians[5,12]. A male preponderance might not only attribute to exposures and lifestyle of man, but also stasis of urine-containing carcinogens in old males with prostatic hyperplasia and urinary retention according to the former study[13,14].We have insufficient proof that cigarette smoking was a risk factor of this crew,because only one smoker was found.
Gross hematuria is the most common clinical presentation of bladder cancer leading to a risk of bladder cancer with 16.5% in general patients[15]. Almost every patient had gross hematuria prior to the diagnosis of bladder cancer treated in time in our study, however five patients were MIBC with at least pT2N0M0 and six patients were dead withthin the follow-up duration. The former study indicated that the risk of bladder cancer was nearly 4% in patients with microscopic hematuria[15]. In view of this situation, we should pay more attention to microscopic hematuria when HIV-infected patients test urinalysis during regular follow-up of AIDS in order to enable to identify bladder cancer patients earlier. Cystoscopy utlized to evaluate the lower urinary tract is a critical screening method for patients who presented hematuria. Cystoscopy was used to learn about conditions of lesions in order to determine the most appropriate surgical plan.In our study cystoscopy showed the most common location of the lesions was trigonum of the bladder,whie the most common tumor location documented by a national corhot sdudy from United states including 4163 patients was the lateral wall[16].Moreover the sdudy showed that trigone tumors were associated with more aggressive tumor stages and worse overall survival[16], which was in line with our results.
We investigated patients’ immunal status in terms of CD4+ T lymphocyte cell count and HIV viral load,which were well controlled due to regular HAART with a median duration of 36 months. For this reason we did not find any evidence on the relationship between immunodeficiency and cancer progression. We preliminarily detected a phenomenon that rapid mean decline of 46% of CD4+ T-lymphocyte cell count was found in four patients underwent T-cell subsets test withthin three days post to the surgery,which was never observed in the two largest previous studies in the United States and France[8,9].We could not draw any conclusions on the this descreasing tendency because of lack of adequate data and tracking of the value.
Bladder cancer stems from the urothelial cells,which accounts for approximately 90% to 95% of urothelial cancer. Bladder cancer consisted of 75% transitional cell carcinoma(TCC)and 25% “variant” histology documented in the former study[17],while our study came up with an extreme proportion of 100% supporting TCC preponderance in HIV-infected patients as well. Tumor grade classified into high grade,low grade,and papillary urothelial neoplasm of low malignant potential described as the 2004 WHO grading system[18]. NMIBC with pT1 stage represents approximately 75% of bladder cancer in general population refer to less aggressive feature. HIV-infected patients in our study was the high rate of MIBC with pT2 stage in 50% and high grade histology in 60%, which was nearly the same as former study in this crew and much higher than the general population reported by physicians[8,19].Patients of bladder cancer are more likely to have aggressive pathological features with regard to bad outcomes in summary.
TURBT is the gold standard treatment for bladder cancer with T1 stage, that not only provides therapeutic benefit but also prognostic information to guide further management of NMIBC[20]. At least 50% of general patients will have residual tumor or missed muscle-invasive tissue in TURBT specimens without muscle invasion, that’s why bladder tumors are more likely to relapse[21]. A high recurrence rate of NMIBC has been estimated over 75% if untreated, and a meta-analysis of published results of randomized clinical trials showed a 39% decline of tumor relapse with intravesical chemotherapy at a median follow-up of 3.4 years[22].In our sudy cancer relapse was seen in 3 patients(50% of T1-stage patients) who accepted regular intravesical chemotherapy of pirarubicin after TURBT,that demonstrated the efficacy of pirarubicin in this crew. Intravesical Bacille Calmette-Guérin (BCG) is the preferred treatment for high-risk NMIBC. Intravesical BCG relies on the activation of immunal cell subsets including CD4+ T lymphocytes as a method of immunotherapy, meanwhile there is a theoretical increased danger of disseminated infection acknowledging the immunodeficiency[23]. We did not recommend intravesical BCG for these reasons. However little efficacy experience had been shared,one HIV-infected patient of bladder cancer with T1 stage received intravesical BCG post to TURBT and had no infectious complications and relapse after BCG infusion in former study[9]. Another study refer to three renal transplant recipients with bladder cancer showed none developed systemic M. bovis infection after BCG infusion, who received prophylactic antituberculosis therapy meanwhile[24]. The results remind us that intravesical BCG can be tried with appropriate precautions.
Treatment for MIBC patients comprises neoadjuvant therapy followed by RC, pelvic lymph node dissection,urinary diversion, and adjuvent therapy when occurs distant metastases including chemotherapy and immunotherapy[25].In our sudy four patients underwent RC, pelvic lymph node dissection, and urinary diversion at the time of initial diagnosis without neoadjuvant chemotherapy because of consideration of increased immunodeficiency and tumor progression. To our surprise, MIBC patients in our series were all dead withthin 2 years due to aggressive pathological features,and the disease progressed much faster than we expected,while MIBC patients in general population is associated with less favorable prognosis with 5-year survival 30%-50% [26].The gap of survival observed between the two population may partly caused by the use of neoadjuvant,because former study showed 15% increasement of survival with neoadjuvant chemotherapy compared to RC alone[27].
We have little experience to share on adjuvant chemotherapy, because patients refused to accept adjuvent chemotherapy maily considering extremely bad prognosis,uncertain efficacy and side effects. We did not recommend the use of immunotherapy as general population, due to the role of PD-1+ T cells in HIV transcription in treated aviremic individuals,concerns of unforeseen side effects and economic factors.However former studies in general population have proved that high mutational burden of bladder cancer makes it susceptible to immunotherapy, particularly with checkpoint inhibitors((PD-1/PD-L1 inhibitors).A recent study showed that no concerning findings were found in HIV-infected patients with advanced cancer treated with checkpoint inhibitors,while checkpoint inhibitors were more likely to have comparable efficacy,tolerable adverse effects, and stable HIV status[28]. In a prospective clinical study including one HIV-infected TCC patient indicated that checkpoint inhibitors had no negative effects on CD4+ T lymphocyte cell count and HIV viral load,but cancer response was not reported[29]. It is quitely regrettable that the study on checkpoint inhibitors in bladder cancer patients with HIV-infected was too rare to draw meaningful conclusions as clinical guidelines.