Case Report/Case Presentation
A 57-year-old man, 45 pack-year smoker presented to the clinic
complaining of gross hematuria. His medical history was significant for
diabetes mellitus, peripheral vascular disease, cardiomyopathy, and
prior cerebral hemorrhage. Also, he underwent a coronary artery bypass
graft (CABG) in September 2019. Otherwise, clinical examination was
insignificant.
The cystoscopy and CT scan (shown in Fig. 1) showed a multifocal bladder
tumor. Transurethral resection (TUR) was performed. The TUR pathology
revealed a stage-T1G3 transitional cell carcinoma, the muscularis was
present but free of tumor, so non-muscle invasive bladder cancer (NMIBC)
was diagnosed. The tumor involved the prostatic urethra. The CT scan
excluded any distant metastases.
After that, the patient received one vial of intravesical Bacillus
Calmette-Guerin (BCG)-Medac™ once a week for 6 weeks. Three months
later, the TUR showed residual tumor fragments, so the patient was
considered BCG-refractory.
Radical cystectomy is the standard of care in such situations. However,
due to the cardiomyopathy, the patient was unfit for the surgery and
also refused it. So, other treatment options were required.
Another TUR was performed and followed by the intravesical injection of
2 g of Gemcitabine once a week for 6 weeks. After 3 months, the
cystoscopy and taken biopsies showed complete response to the treatment
and no evidence of tumor. No side effects were encountered during the
therapeutic course.
Discussion/Conclusion
Non-muscle invasive bladder cancer (NMIBC) remains a therapeutic
challenge, especially in the era of BCG shortage. Although the
transurethral resection (TUR) of the tumor followed by intravesical BCG
injection has long been the standard of care for NMIBC, the treatment
fails in about 40-50% of patients [5].
The classifications of BCG failure are shown in Table 1. [6] [7]
Radical cystectomy is indicated in cases of BCG failure and provides a
92% disease-free survival when early performed [8]. However,
post-surgical quality of life assessment showed many physical, mental,
and social health problems in patients who underwent the surgery
[9]. So many people refuse such intervention. On the other hand,
many of them are unfit for surgery due to cardiac or other health
issues.
As an alternative to surgery, bladder-sparing treatments include a
second course of BCG, intravesical mitomycin C (MMC), intravesical
chemotherapy with gemcitabine, and a few other options [10].
Gemcitabine (GEM) has now level-one evidence as an effective drug for
bladder cancer [11]. When used intravesically, GEM reaches low
plasma levels which reduces systemic toxicity [12].
A systematic review and meta-analysis compared the efficacy and safety
of intravesical GEM versus MMC for NMIBC and demonstrated that using GEM
is associated with a statistically significant decrease in tumor
recurrence rate and reduction in local toxicity compared with MMC
[13]. In addition, MMC is an expensive drug that cannot be
affordable in some low-income countries.
Ye et al conducted a similar meta-analysis on five clinical trials with
an overall 386 bladder cancer patients, comparing GEM to BCG. The
results showed no statistically significant difference in tumor
recurrence rates, but GEM was associated with significantly lower rates
of dysuria and hematuria in comparison with BCG [14].
Our patient suffers from severe cardiomyopathy that makes surgery
contraindicated. He also refused the radical cystectomy due to the poor
postoperative quality of life.
Considering the reasons mentioned above, we preferred GEM over other
treatment options after the first BCG failure. The treatment course led
to a complete pathologic response with no side effects. A 6-month
follow-up showed no tumor recurrence, but a longer follow-up time is
needed to determine the long-term efficacy of the treatment.
In our case, we aim to shine the light on the promising role of GEM in
treating resistant bladder cancers and avoiding radical cystectomy
complications.
Since our study was performed on one patient only, it provides
relatively weak –but important- evidence. So, to formulate definitive
recommendations, larger and higher-quality studies are required.
Author Contributions:
Fouad Nahhat: wrote the abstract, introduction, and discussion, and
participated in the literature review.
Modar Doyya: wrote the case presentation, designed the figure, and
participated in the literature review.
Hazem Ksiri: participated in patient’s treatment and supervised the
manuscript preparation scientifically and academically.