Bladder cancer (BC) is the tenth most commonly diagnosed cancer worldwide. Approximately 75%
of patients with BC present with disease confined to the mucosa (stage Ta or CIS) or
submucosa (stage T1); for younger patients (<40 year) this Percentage is even higher (Babjuk
et al., 2022).
About 40%-80% of NMIBC recur within 6-12 months when managed with TURBT alone, and 10%-25% of
the patient's progress to muscle invasive disease. Intravesical therapy enables delivery of
high local concentrations of a therapeutic agent within the bladder, which could potentially
destroy viable tumor cells that remain following TURBT (Ye Z, et al., 2018 and Daneshmand et
al., 2022).
The Intravesical BCG injection can reduce the recurrence rate by about 30-40%. For
intravesical therapy, chemotherapy drugs such as mitomycin C, gemcitabine, and epirubicin can
be used post-TURBT, which is a good alternative treatment for BCG or a second-line treatment
(Ansari et al., 2022).
The BCG vaccine was firstly developed by Albert Calmette over a hundred years ago. Its effect
on bladder cancer was proposed by Dr. Alvaro Morales about forty years ago. In 1990, BCG was
approved by the Food and Drug Administration (FDA) for the treatment of NMIBC and then became
the first-line drug in NMIBC up to now (Ansari et al., 2022).
Due to worldwide shortage of BCG, there is a clinical need to develop novel intravesical
agents and application forms in order to improve the oncological outcomes in non-muscle
invasive bladder cancer (NMIBC). Gemcitabine has been investigated in various clinical
trials. It has proven to be superior to BCG re-challenge and mitomycin (MMC) in
BCG-unresponsive high-risk NMIBC (Gakis, 2022).
Gemcitabine is a nucleoside analogue with cytotoxic activity mediated by inhibition of DNA
synthesis followed by cell apoptosis. The majority of trials examining gemcitabine have been
in the setting of prior BCG failure (Balasubramanian et al., 2022).
NMIBC represents a significant global therapeutic challenge, particularly in the era of
international BCG shortage due to manufacturing issues. Induction and maintenance
intravesical BCG remains the historical gold standard for patients with intermediate or
high-risk NMIBC. However, clinicians may be forced to consider alternatives given the current
BCG shortage. Attempts to rationalize its use, including dose frequency reduction, have
resulted in inferior outcome. Accordingly, there is considerable interest worldwide in
assessing alternate approaches to improve oncologic outcomes for patients with NMIBC
(Balasubramanian et al., 2022).
The majority of trials examining gemcitabine have been in the setting of prior BCG failure.
To our knowledge there are only four trials evaluating initial intravesical gemcitabine
without prior BCG usage. Porena et al., 2010 included only 32 patients; Bendary et al. 2011
included 40 patients; Gontero et al., 2013 included 61 patients and Prasanna et al., 2017
included 51 patients. Depending on this fact, we need a well-designed prospective trial
including a large number of patients with reasonable follow-up period to estimate the actual
benefits and hazards of intravesical gemcitabine injection.
