Role of Intravesical Gemcitabine versus Mitomycin C as Immediate Intravesical Therapy post TURBT in Non-Muscle Invasive Bladder Cancer: A Prospective Exploratory Observational Study

With 18.1 million new cases & around 9.6 million deaths in 2018,

cancer poses a significant disease burden worldwide. Urinary

bladder cancer in itself is 3% of the new cancer diagnoses and 2.1%

to the total cancer mortality [1].

90% of all bladder cancers are of urothelial subtype which has

tobacco smoking as the major contributing factor [2]. Several

occupations having exposure to aromatic amines (painters,

plumbers etc.), recurrent Urinary Tracts Infections, indwelling

catheters, drugs such as cyclophosphamide & environmental

exposure in the form of arsenic in drinking water are well known risk

factors for bladder cancers[2].

At presentation approximately 70% of bladder cancers are Non

Muscle Invasive Bladder Cancer (abbr. NMIBC) while others are

Muscle Invasive Bladder Cancer (abbr. MIBC) or metastatic [3]. The

typical initial management approach is cystoscopic visualisation,

followed by Trans Urethral Resection of Bladder Tumor (abbr.

TURBT). The aim of treatment in NMIBC group focuses on reducing

recurrence, preventing disease progression & minimising the

adverse events during the treatment. To prevent recurrence,

intravesical instillation of chemotherapeutic agents in the first 24

hours following TURBT is recommended and has shown favourable

results for the same. [4]

The US FDA has approved two drugs for the purpose of immediate

post-operative Intravesical Chemotherapy- Mitomycin C and

Gemcitabine, with Gemcitabine as the latest entry in the current

edition of the National Comprehensive Cancer Network (abbr.

NCCN) guidelines. Both are cytotoxic agents known to affect DNA integrity via distinctly different mechanisms.

Gemcitabine, a nucleoside analogue, undergoes efficient

phosphorylation and the resultant decrease of deoxycytidine

triphosphate further accelerates Gemcitabine nucleotide formation

and at the same time decreases their clearance via deaminase.

When incorporated into DNA, these Gemcitabine nucleotides lead to

loss of viability of the cells [5].

Mitomycin C on the other hand leads to DNA adducts formation in

cancer cells via formation of reducing equivalents leading to their

subsequent destruction [6].

Considering the current lack of literature evaluating these two drugs

when used as a single agent chemotherapy in the perioperative

period we want to conduct a prospective observational study on

Intravesical Gemcitabine versus Mitomycin C as Immediate

Intravesical Therapy in NMIBC patients undergoing TURBT to test

whether Gemcitabine provides any benefit over Mitomycin C . This

may aid in further research and clinical decision making in the future.