Bacillus Calmette-Guerin (BCG) immunotherapy, following the transurethral resection of the bladder tumour (TURBT), is the current gold-standard adjuvant treatment for the non-muscle-invasive bladder cancer (NMIBC), stratified as high-risk of progression. European Association of Urology (EAU) 2020 Guidelines highlight the BCG therapy efficacy in preventing tumour recurrence and progression and do not recommend any treatment modification in elderly patients.3
Therefore in our study, we aimed to analyze the oncological outcomes of patients over 80 years of age with high-grade T1 bladder cancer and assess the role of adjuvant BCG therapy. Like other authors, we also report suboptimal BCG use, which is especially striking in the elderly. In our study, only 48% of patients received at least BCG induction, whereas barely 30% were treated with one or more BCG maintenance courses. The patient’s non-compliance (34%) and presence of comorbidities (17%) were the leading causes of not receiving BCG.
The analyzed cohort of patients was characterized by a very high median age (85; IQR 82.5-88) and 15% of individuals were over 90 years old at the time of TURBT. Notably, some of the patients belonged to the highest-risk NMIBC group, as 20% of individuals had concomitant CIS, whereas 23% presented with multiple and large T1HG tumours.
To assess the role of BCG therapy in the selected cohort, patients who received BCG (N=30) and those who did not (N=30) were compared. Patients included in both groups underwent a case-control matching, based on age and Charlson comorbidity score. BCG-treated patients presented more often with concomitant CIS (20% vs 3%; p=0.047) and residual high-grade tumor in re-TURBT (56.5% vs 25%; p=0.037). Additionally, patients suffered from various comorbidities, with coronary artery disease and a history of other malignancies being more prevalent in the BCG-treated group (80% vs 50% and 30% vs 7% respectively). Despite the aforementioned adverse factors and suboptimal BCG maintenance, in the majority of cases, patients who received at least an induction course achieved better oncological outcomes than the untreated group. The rates of disease recurrence (53%) and cancer-specific mortality (10%) were significantly lower in patients who received BCG when compared to individuals not treated with BCG (80% and 40% respectively). Rates of NMIBC progression to muscle-invasive disease were also lower in BCG-receivers (30% vs 50%), although the border of statistical significance was not reached (p=0.11). BCG-treated individuals demonstrated better cancer-specific survival, but we did not observe a statistically significant benefit in terms of recurrence- and progression-free survival. This might be attributed to the low sample size and censored data at the last follow-up, which was inconsistent amongst patients. Despite its obvious limitations, our study confirms the benefit of BCG immunotherapy in T1HG NMIBC, regardless of the patient’s age and comorbidities.
It must also be noted that BCG therapy is not devoid of possible complications. In our study, we observed clinically significant side effects of BCG use in 32% of patients and BCG intolerance in 19%.
Previous studies suggest a higher risk of complications in elderly patients. Heiner et al. reviewed a clinical course of 58 patients undergoing BCG and found that the complication rates were 17.6% and 48.6% for those below the age of 70 and over 70 years old, respectively. Individuals who developed complications (mean age 76.0 years) were significantly older than those who did not (70.3 years).4 Such incidence of side effects may notably deteriorate treatment compliance, leading to high discontinuation rates. Moreover, elderly patients might experience quality of life impairment due to obligatory regular visits and treatment side effects. Currently, the potential risk of healthcare-associated SARS-CoV2 infection constitutes yet another obstacle to scheduled BCG administration.
We have also evidenced the utility of the Charlson comorbidity index (CCI) in predicting oncological outcomes (PFS and CSS) and, not surprisingly, overall survival. Therefore, routine CCI estimation might be of clinical value in elderly patients with bladder cancer to achieve suitable personalized therapy and a tailored follow-up.
The aforementioned data highlight the issue of suboptimal BCG treatment and its relevance in the elderly with T1HG NMIBC. Efforts should be made to increase the rate of BCG receivers, especially among those over 80 years old. At the time of diagnosis and during an induction course, counseling to explain the importance of maintenance should be offered. Moreover, patients and their families should be educated on the relevance of BCG therapy and its ability to prolong survival, despite possible inconveniences and side effects. Close cooperation between general practitioners and urologists should be taken into consideration to maximize the patient’s compliance and chances of completing the treatment. Finally, medical facilities shall provide patients with regular reminders of upcoming BCG instillations.
Written by: Karolina Garbas; Aleksander Ślusarczyk; Piotr Zapała; Łukasz ZapałaPiotr Radziszewski, Department of General, Oncological and Functional Urology, Medical University of Warsaw, Poland
- Saginala K, Barsouk A, Aluru JS, Rawla P, Padala SA, Barsouk A. Epidemiology of Bladder Cancer. Med Sci Basel Switz. 2020 Mar 13;8(1).
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019 Jan;69(1):7–34.
- Professionals S-O. EAU Guidelines: Non-muscle-invasive Bladder Cancer [Internet]. Uroweb. [cited 2020 Dec 28]. Available from: https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/.
- Heiner JG, Terris MK. Effect of advanced age on the development of complications from intravesical bacillus Calmette-Guérin therapy. Urol Oncol Semin Orig Investig. 2008 Mar;26(2):137–40.
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