PMID- 37745737
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230926
IS  - 2168-8184 (Print)
IS  - 2168-8184 (Electronic)
IS  - 2168-8184 (Linking)
VI  - 15
IP  - 9
DP  - 2023 Sep
TI  - Adjuvant Hyperthermic Intravesical Chemotherapy in Intermediate- and High-Risk 
      Non-muscle Invasive Bladder Cancer.
PG  - e45672
LID - 10.7759/cureus.45672 [doi]
LID - e45672
AB  - INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is a frequently 
      diagnosed neoplasm, which is typically managed with transurethral resection of 
      bladder tumor (TURBT) eventually followed by intravesical therapies. Bacillus 
      Calmette-Guerin (BCG) is used as first-line adjuvant treatment in high- (HR) and 
      intermediate-risk (IR) NMIBC, although, in the latter, mitomycin C (MMC) may also 
      be used. Multiple limitations to the use of BCG encouraged the search for 
      therapeutic alternatives. In this context, hyperthermic intravesical chemotherapy 
      with MMC (HIVEC-MMC) emerged as a promising therapy in the adjuvant setting for 
      NMIBC. The aim of our study was to evaluate the tolerability, compliance, and 
      survival outcomes of HIVEC-MMC in patients with IR- and HR-NMIBC. MATERIAL AND 
      METHODS: This was a single-center retrospective analysis of IR- and HR- NMIBC 
      patients who received HIVEC-MMC after TURBT between August 2018 and August 2022. 
      Levels of risk stratification were defined using the European Association of 
      Urology (EAU) criteria. The protocol consisted of four weekly HIVEC-MMC 
      instillations (induction) followed by six monthly instillations (maintenance). 
      The primary outcomes were to evaluate the tolerability and compliance with the 
      HIVEC-MMC protocol and secondary outcomes were disease-free survival (DFS) and 
      overall survival (OS). For the purpose of statistical analysis, methods of 
      descriptive statistics, survival analysis (Kaplan-Meier estimation), and 
      multivariate analysis (Cox regression, and binary logistic regression) were used. 
      RESULTS: Fifty-seven patients were enrolled with a median age of 67.9 (34.4-83.5) 
      years old. In this cohort, 40 patients (70.2%) had primary tumors. At the time of 
      referral for HIVEC-MMC, the majority of the patients had IR-NMIBC (n= 33, 57.9%). 
      A total of 41 patients (71.9%) completed the HIVEC-MMC protocol. Disease 
      recurrence and adverse events (AEs) were the most common reasons to stop the 
      protocol. After a median follow-up of 31 months (95% CI, 5.0-54.0), 32 patients 
      (61.4%) were disease-free, 22 (38.6%) experienced recurrent disease and six 
      patients (10.5%) died, although only one death was directly attributable to 
      bladder cancer. The median DFS was 42 months (95% CI, 28.0-56.0). Completion of 
      the HIVEC-MMC maintenance phase protocol stood as a predictive factor for DFS (44 
      months, 95% CI 29.1-58.9 vs. 14 months, 95% CI 0.0-29.6, p < 0.001; HR 4.48, 95% 
      CI 1.65-12.15). The median OS was not reached; the 24- and 48-month OS were 92.6% 
      and 82.7%, respectively. EAU risk group, ECOG-PS, and completion of HIVEC 
      protocol were found to be significant predictive factors of OS but lost their 
      significance on multivariate analysis. However, if we exclude those who 
      experienced recurrence during the maintenance phase protocol, treatment 
      completion had a significant positive impact on OS (HR: 42.8, 95% CI 
      1.75-1045.072, p= 0.021). CONCLUSIONS: Our study suggests that HIVEC is a secure 
      and well-tolerated treatment with promising efficacy data, making this 
      therapeutic approach a feasible option in IR- and HR-NMIBC patients, mainly in 
      those who cannot tolerate or have contraindications to BCG therapy, but also as 
      an alternative during BCG shortages.
CI  - Copyright (c) 2023, Magalhaes et al.
FAU - Magalhaes, Joana C
AU  - Magalhaes JC
AD  - Medical Oncology, Instituto Portugues de Oncologia de Coimbra Francisco Gentil, 
      E.P.E., Coimbra, PRT.
FAU - Sousa, Maria
AU  - Sousa M
AD  - Medical Oncology, Centro Hospitalar Universitario do Porto, Porto, PRT.
FAU - Basto, Raquel
AU  - Basto R
AD  - Medical Oncology, Centro Hospitalar Vila Nova de Gaia/Espinho, Gaia, PRT.
FAU - Fraga, Teresa
AU  - Fraga T
AD  - Medical Oncology, Instituto Portugues de Oncologia de Coimbra Francisco Gentil, 
      E.P.E., Coimbra, PRT.
FAU - Gomes, Ines
AU  - Gomes I
AD  - Medical Oncology, Instituto Portugues de Oncologia de Coimbra Francisco Gentil, 
      E.P.E., Coimbra, PRT.
FAU - Fernandes, Catarina
AU  - Fernandes C
AD  - Medical Oncology, Centro Hospitalar Universitario de Sao Joao, Porto, PRT.
FAU - Mariano, Monica
AU  - Mariano M
AD  - Medical Oncology, Centro Hospitalar e Universitario de Coimbra, Coimbra, PRT.
FAU - Paulo, Judy
AU  - Paulo J
AD  - Medical Oncology, Instituto Portugues de Oncologia de Coimbra Francisco Gentil, 
      E.P.E., Coimbra, PRT.
FAU - Madeira, Pedro
AU  - Madeira P
AD  - Medical Oncology, Instituto Portugues de Oncologia de Coimbra Francisco Gentil, 
      E.P.E., Coimbra, PRT.
FAU - Sousa, Gabriela
AU  - Sousa G
AD  - Medical Oncology, Instituto Portugues de Oncologia de Coimbra Francisco Gentil, 
      E.P.E., Coimbra, PRT.
LA  - eng
PT  - Journal Article
DEP - 20230921
PL  - United States
TA  - Cureus
JT  - Cureus
JID - 101596737
PMC - PMC10512434
OTO - NOTNLM
OT  - adjuvant intravesical chemotherapy
OT  - bacillus calmette-guerin
OT  - hyperthermic intravesical chemotherapy
OT  - mitomycin c
OT  - non-muscle invasive bladder cancer
COIS- The authors have declared that no competing interests exist.
EDAT- 2023/09/25 06:43
MHDA- 2023/09/25 06:44
PMCR- 2023/09/21
CRDT- 2023/09/25 05:06
PHST- 2023/09/20 00:00 [accepted]
PHST- 2023/09/25 06:44 [medline]
PHST- 2023/09/25 06:43 [pubmed]
PHST- 2023/09/25 05:06 [entrez]
PHST- 2023/09/21 00:00 [pmc-release]
AID - 10.7759/cureus.45672 [doi]
PST - epublish
SO  - Cureus. 2023 Sep 21;15(9):e45672. doi: 10.7759/cureus.45672. eCollection 2023 
      Sep.