(1) Background: Intravesical chemotherapy is the standard of care in intermediate-risk non-muscleinvasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost, and practice patterns. Epirubicin (EPI), one of these agents, has been used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability are still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: This study aimed to systematically review the efficacy and safety profile of Epirubicin (EPI) in the management of non-muscle invasive bladder cancer (NMIBC) compared to other adjuvant therapies. A systematic search of the PUBMED, Web of Science, clinicaltrials.gov, and Google Scholar databases was conducted on 31 December 2023, using relevant terms related to EPI, bladder cancer, and NMIBC. The inclusion criteria targeted studies that evaluated patients treated with EPI following the transurethral resection of bladder tumors (TURBT) for NMIBC and compared oncological outcomes such as recurrence and progression with other adjuvant therapies, including Mitomycin C (MMC), Gemcitabine (GEM), and Bacillus Calmette-Guérin (BCG). Additionally, studies investigating the safety profile of EPI administered intravesically at room temperature and under hyperthermia, as well as oncological outcomes associated with hyperthermic intravesical EPI administration, were included. (3) Results: Eleven studies reported adverse events after adjuvant intravesical instillations with EPI; the most frequently reported adverse events included cystitis (34%), dysuria, pollakiuria, hematuria, bladder irritation/spasms, fever, nausea and vomiting, and generalized skin rash (2.3%). Nine studies compared EPI to BCG in terms of recurrence and progression rates; BCG instillations showed a lower recurrence rate compared to EPI, with limited or non-significant differences in progression rates. Two studies found no significant differences between EPI and MMC regarding progression and recurrence rates. One study showed statistically significant lower recurrence and progression rates with GEM in high-risk NMIBC patients. Another study found no significant differences between EPI and GEM regarding recurrence and progression. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are interesting newcomers.

(1) Background: Intravesical Chemotherapy is standard of care in intermediate risk non-muscle-invasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost and practice patterns. Epirubicin (EPI), one of these agents is used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability is still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: A systematic search of PUBMED, Webofscience, clinicaltrials.gov, and Google Scholar databases was performed on December 31, 2023. We reviewed 28 studies that included patients treated EPI after TURBT (transurethral resection of bladder tumors) for NMIBC and who compared oncological outcomes such as recurrence and progression to other adjuvant treatment such as Mitomycin C (MMC), Gemcitabine (GEM) and BCG. Further, we looked at the safety profile of EPI at room temperature under hyperthermia intravesically and at the oncological outcomes when administrated with hyperthermia; (3) Results: When compared to other chemotherapeutics (MMC/GEM), EPI seemed to be equally effective; however, EPI seems less effective in preventing disease management recurrence compared to BCG intravesical. The most common adverse events of EPI include cystitis, dysuria, and pollakiuria. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are promising newcomers.

Introduction: Bladder cancer (BC) ranks as the 10th most common cancer globally, predominantly affecting older adults. Non-muscle invasive BC (NMIBC) are known for high recurrence and progression rates despite standard treatments. Objective: This study assesses the efficacy of chemohyperthermia with epirubicin in Bacillus Calmette–Guérin (BCG)-naïve patients with either primary or recurrent NMIBC. Methods: We conducted a prospective pilot study on this cohort using the bladder wall thermochemotherapy – UniThermia platform, with a follow-up period of 24 months. Nine NMIBC patients (88.89% male; mean age: 70.22 ± 11.82 years) were prospectively enrolled. Inclusion criteria were NMIBC stage Ta–T1 with BCG-naïve status; patients with carcinoma in situ (CIS) were excluded. Results: Tumor staging revealed pTa in six patients and pT1 in three patients; tumor grading included G1 (11.11%) and G2 (88.89%). No CIS was detected. All patients received six weekly chemohyperthermia instillations. At the 24-month follow-up, four patients (44.4%) achieved a complete response with no recurrences; all remained alive with no disease progression. All recurrences were low-grade pTa. Conclusion: These findings suggest that chemohyperthermia with epirubicin may offer therapeutic advantages over intravesical BCG or conventional chemotherapy, especially for BCG-intolerant or refractory patients. Study limitations include the small sample size and limited follow-up duration. Further multicenter studies are warranted to validate these preliminary results. Overall, chemohyperthermia with epirubicin appears to be a promising alternative for the management of recurrent NMIBC when standard BCG treatment is ineffective or unavailable.